Issue 4, 2009

By the abstracts:

"Association of Apolipoprotein E and Angiotensin Converting Enzyme Gene Polymorphisms with the Multidimensional Impairment in Older Patients" by Alberto Pilotto, Maria G. Matera, Luigi Ferrucci, Daniele Sancarlo, Gioacchino Leandro, Grazia D'Onofrio, Davide Seripa, Filomena Addante, Marilisa Franceschi, and Bruno Dallapiccola. 1900 geriatric patients. ApoE4 at 1.79 odds ratio with severe risk of mortality according to some multidimensional impairment index (MPI) they developed. ACE D/D at 1.42. Combo at 2.85. But then it says no association between APO and ACE polymorphisms and 2-year mortality, so not sure what their MPI is measuring.

"Thymectomy in Early Childhood: A Model for Premature T Cell Immunosenscence?" by Manuela Zlamy and Martina Prelog. What the title says. Parallels of decreased proportion of naive T cells and recent thymic emigrants, compensatory proliferation of mature T cells, decreased T-cell receptor repertoire and slower response to antigens and vaccinations.

"Neuroprotective Effect of Long-term NDI1 Gene Expression in a Chronic Mouse Model of Parkinson Disorder" by Jennifer Barber-Singh, Byoung Boo Seo, Eiko Nakamaru-Ogiso, Yuen-Sum Lau, Akemi Matsuno-Yagi, and Takao Yagi. They insert a NADH-quinone oxidoreductase (NDI1) from yeast into mice's mitochondria. "Parkinson's"-induced versions do better with the modification than controls.

"Morphology and Myofiber Composition of Skeletal Musculature of the Forelimb in Young and Aged Wild Type and Myostatin Null Mice" by Mohamed I. Elashry, Anthony Otto, Antonios Matsakas, Salah E. El-Morsy, and Ketan Patel. What the title says, plus comparisons with rats and comparison across ages.

"Live Fast, Die Young: New Lessons in Mammalian Longevity" by Lynne S. Cox. Full text available. Commentary on two at-the-time recent results: the lengthening of lifespan in mice by rapamycin and the partial results of the Wisconsin lifespan study of CR on rhesus monkeys. The rapamycin study is interesting because it was started on old mice (600 days), but the effect is small (lifespan extension at 90% mortality of 9% for males, 14% for females). Interesting note that the doses were huge (2.24mg/kg vs 40 micrograms/kg human immunosuppresive doses). There seems to have been some small dodginess with food used and lifespan prior to start of dosing. Also interesting that rapamycin had higher incidence of cancer and cardiovascular deaths. Some talk about paths of action (lower protein synthesis). No mention of NIH study on CR.


The thesis review section looks at thesis on:

• 3d-polymer models seeded with stem cells to grow articular cartilage
• Following the transplantation of endothelial progenitor cells into sheep in-utero, where they grow into the liver and intestinal cells
• Mostly a review of the field of small molecules that guide differentiation of stem cells, including a new one that differentiates mouse ESCs to dopamine neuron progenitor cells
• Tour-de-force on dealing with neural stem cells, going from extraction from the brain, expansion, genetic modification, reinsertion and tracking
• Human hair follicle stem cells, its similarity to mesenchymal stem cells, and exploration of differentiation potential.
• Injecting MSCs into brains of mice to produce ApoE. Naive one doesn't work but is inducible by dexamethasone. Works, but only in immunosuppressed mice.

Issue 3, 2009

By the abstracts:

"Weight Loss in Obese Men Is Associated with Increased Telomere Length and Decreased Abasic Sites in Rectal Mucosa" by Nathan J. O'Callaghan, Peter M. Clifton, Manny Noakes, and Michael Fenech. One year study putting obese men on CR and making them drop 10kg. Dunno how many men. Telomere length from cells taken from colon biopsies were 10 times longer at the end of the study, and abasic sites in the DNA dropped by two thirds. Initial telomere length was only weakly negatively correlated with BMI so not sure how much this is a "change" effect. The effects sound too big.

"Characteristics of 400-Meter Walk Test Performance and Subsequent Mortality in Older Adults" by Sonja Vestergaard, Kushang V. Patel, Stefania Bandinelli, Luigi Ferrucci, and Jack M. Guralnik. Time to walk 400 metres and its variance were predictors of 6-year mortality in 1000 Italians >65 years old after adjusting for age, sex, MMSE, depression, education, smoking, BMI, sedentarity, disease burden and lower extremity performance (that last one is surprising).

"The Expression of CYP2D22, An Ortholog of Human CYP2D6, in Mouse Striatum and Its Modulation in 1-Methyl 4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinson's Disease Phenotype and Nicotine-Mediated Neuroprotection" by Seema Singh, Kavita Singh, Devendra Kumar Patel, Chetna Singh, Chandishwar Nath, Vinod Kumar Singh, Raj Kumar Singh, and Mahendra Pratap Singh. Brain stuff.

"Nuclear DNA Damage as a Direct Cause of Aging" by Benjamin P. Best. Trying to build a case for nDNA damage as a cause of aging. Might need to find it and read it...ok. The paper is a collection of correlations between aging and nDNA damage. No claim of causality is made but a call to maybe-look-into-it since SENS dismisses nDNA as non-important outside of cancer and senescence. The paper is hard to summarise since it is almost in point form to begin with.

"Age-Dependent Down-Regulation of Mitochondrial 8-Oxoguanine DNA Glycosylase in SAM-P/8 Mouse Brain and Its Effect on Brain Aging" by Feng Tian, Tan-Jun Tong, Zong-Yu Zhang, Michael A McNutt, and Xin-Wen Liu. They compare mitochondrial 8-Oxoguanine DNA glycosylase (OGG1) expression and COX III expression in the brains of SAM-P/8, an accelerated-aging mouse, and SAM-R/1, its normally-aging counterpart, and find higher downregulation in SAM-P/8. They say this causes imbalances in mtDNA damage repair systems.

"How Is Mutant Mitochondrial DNA Clonally Amplified? Much New Evidence, Still No Answers" by Aubrey D.N.J. de Grey. Some commentary on how recent results affect two theories of clonal expansion of mitochondria with mtDNA mutations: his theory of clonal mitochondrial expansion (mt survive due to low superoxide creation) and another theory that says that mt with mtDNA deletions replicate fastest. Three pieces of new information:

• Clonal expansion in fast-dividing gut stem cells and slow dividing stem cells. Point mutations mostly. Doesn't go with either theory.
• mt with larger deletions replicate faster in mice. Goes nicely with deletion-related theory, but against superoxide-dependent since the size of deletion shouldn't matter
• Protein parkin binds to dysfunctional mt promoting their destruction. Goes against superoxide theory since it predicts the opposite (that mutants will survive). Reasonable attempt at salvaging theory by type of dysfunction in experiment (uncoupled, not respiratory chain malfunction)

The first thesis in the thesis discussion section is about grafts into rat hearts. They try genetically adding a growth factor receptor into the cells-to-be-grafted, and also building 3D grafts consisting of either pure cardiomyocytes and of cardiomyocytes, endothelial cells and fibroblasts.

Issue 2, 2009

By the abstracts:

"Stimulation of Autophagy by Antilipolytic Drugs May Rescue Rodents from Age-Associated Hypercholesterolemia" by Sara Straniero, Gabriella Cavallini, Alessio Donati, Valentina Pallottini, Chiara Martini, Anna Trentalance, and Ettore Bergamini. Fasted rats overnight and injected them with 3,5-dimethylpyrazole, an antilipolytic agent, supposedly to induce macroautophagy. Total LDL, HDL and triglycerides were lowered to young rat levels. They say this happened through restoration of high LDL receptor levels in the rats' livers. Not sure if they confirmed autophagy.

"Adeno-Associated Virus-8-Mediated Intravenous Transfer of Myostatin Propeptide Leads to Systemic Functional Improvements of Slow but Not Fast Muscle" by Keith Foster, Ian R. Graham, Anthony Otto, Helen Foster, Capucine Trollet, Paul J. Yaworsky, Frank S. Walsh, Dale Bickham, Nancy A. Curtin, Susannah L. Kawar, Ketan Patel, and George Dickson. This was in mice. Muscle mass went up all around, with larger fibres, but only the slow muscle increased force. Very cool.

"Association of the FOXO3A Locus with Extreme Longevity in a Southern Italian Centenarian Study" by Chiara Viviani Anselmi, Alberto Malovini, Roberta Roncarati, Valeria Novelli, Francesco Villa, Gianluigi Condorelli, Riccardo Bellazzi, and Annibale Alessandro Puca. Tons of cites. Validation study in Italian centenarian population of FOXO3A SNPs (rs2802292, rs2764264, and rs13217795) associated with longevity in Hawaiian Japanese population. These studies always sound statistically suspect. Anyway, odds ratio 1.5 on minor allele of rs2802288 (which one's minor is hard to tell since it's an almost fifty-fifty split), a proxy for rs2802292.

"A Comprehensive Review on Mesenchymal Stem Cell Growth and Senescence" by Krzysztof Książek. Again, tons of cites. Reading the abstract of a "comprehensive review" is not going to tell me shit. Meant to be about advances in getting MSCs to expand in vitro.

"Age-Associated Decrease of High-Density Lipoprotein-Mediated Reverse Cholesterol Transport Activity" by Hicham Berrougui and Abdelouahed Khalil. Review paper of what the title says.

"Advocating Vaccination of Adults Aged 60 Years and Older in Western Europe: : Statement by the Joint Vaccine Working Group of the European Union Geriatric Medicine Society and the International Association of Gerontology and Geriatrics–European Region" by Jean-Pierre Michel, Christian Chidiac, Beatrix Grubeck-Loebenstein, Robert W. Johnson, Paul Henri Lambert, Stefania Maggi, Robert Moulias, Karl Nicholson, and Hans Werner. Vaccines are good.

"Characteristics, Formation, and Pathophysiology of Glucosepane: A Major Protein Cross-Link" by Johan Svantesson Sjöberg and Sven Bulterijs. What the title says. Glucosepane is the most common AGE. It cross-links collagen and it lives in the extracellular space.

In the thesis review section, the first thesis is about cranial irradiation stopping hippocampal neurogenesis, and using this fact to investigate what hippocampal neurogenesis is needed for, and also what is stopping it (inflammation seems to be the answer to the last one, specifically monocyte chemoattractant protein 1).

Issue 1, 2009

By the abstracts:

"Ascorbate Recycling by Erythrocytes During Aging in Humans" by Syed Ibrahim Rizvi, Kanti Bhooshan Pandey, Rashmi Jha, and Pawan Kumar Maurya. Red blood cells contain ascorbate free radical (AFR) reductase (I had no idea about this). They have higher activity with age and this activity is correlated with plasma membrane redox system activity (I don't understand what activity means here. I thought red blood cells didn't have a nucleus, so it can't be upregulated, can it?). They say it's to compensate and keep a good level of vitamin C in the plasma.

"Increased Plasma Neutrophil Gelatinase-Associated Lipocalin Levels Predict Mortality in Elderly Patients with Chronic Heart Failure" by Davide Bolignano, Giorgio Basile, Pina Parisi, Giuseppe Coppolino, Giacomo Nicocia, and Michele Buemi. Neutrophil gelatinase-associated lipocalin is some cytokine. NGAL > 783 ng/mL had 4 times higher mortality in 2-year followup of 46 people with CHF. Levels in non-CHF people much lower (38).

"Lysophosphatidylcholine Enhances Oxidative Stress Via the 5-Lipoxygenase Pathway in Rat Aorta During Aging" by Yani Zou, Dae Hyun Kim, Kyung Jin Jung, Hyoung-Sam Heo, Chul Hong Kim, Hyung Suk Baik, Byung Pal Yu, Takako Yokozawa, and Hae Young Chung. What the title says.

"Plasma Polyunsaturated Fatty Acids and Age-Related Physical Performance Decline" by Angela M. Abbatecola, Antonio Cherubini, Jack M. Guralnik, Cristina Andres Lacueva, Carmelinda Ruggiero, Marcello Maggio, Stefania Bandinelli, Giuseppe Paolisso, and Luigi Ferrucci. 330 old people. Higher PUFA, n-3 PUFA and n-6 PUFA associated with higher leg functionality. Lots of other fishy-sounding correlations quoted, all pushing for higher PUFA and higher n-3/n-6 ratio.

"Survival in Frontotemporal Lobar Degeneration and Related Disorders: Latent Class Predictors and Brain Functional Correlates" by B. Borroni, M. Grassi, C. Agosti, E. Premi, A. Alberici, B. Paghera, S. Lucchini, M. Di Luca, D. Perani, and A. Padovani. Use of a mixture model to predict mortality of dementia patients.

"Unexpected Regeneration in Middle-Aged Mice" by Brandon Reines, Lily I. Cheng, and Polly Matzinger. Full text available for this one. They claim, with pictures, that the standard B6 and BALB/c mice regenerate their ears after getting them hole-punched too, not just the MRL mice that had become famous for it earlier. The difference is that they need to be middle-aged for it to work, it doesn't work when the hole-punching is done when young, like with the MRL strain. They think the regeneration happens in all strains once the mice reach a certain size. In the process, they develop a better hole-puncher and a quicker hole-size measuring system. Very strange that this was never noticed before.

The first page of de Grey's review of theses looks at one which studies the use of the phiC31 integrase as a gene transfer mechanism. It targets this site which has lots of instances on mammalian genomes, and they also demonstrate retargetting through directed evolution. Sounds promising (but CRISPR).

Issue 6, 2008

By the abstracts:

"Long-Term Treatment with a Chinese Herbal Formula, Sheng-Mai-San, Improves Cardiac Contractile Function in Aged Rats: The Role of Ca2+ Homeostasis" by Guang-Qin Zhang, Hui Wang, Wen-Tao Liu, Hang Dong, Wang-Fun Fong, Li-Min Tang, Yun-Hua Xiong, Zhi-Ling Yu, and Kam-Ming Ko. Tracks changes to calcium ion-related properties in old rat heart cells when given Sheng-Mai-Yin.

"Age-Dependent Signature of Metallothionein Expression in Primary CD4 T Cell Responses Is Due to Sustained Zinc Signaling" by Won-Woo Lee, Dapeng Cui, Marta Czesnikiewicz-Guzik, Ricardo Z.N. Vencio, Ilya Shmulevich, Alan Aderem, Cornelia M. Weyand, and Jörg J. Goronzy. Transcriptome analysis of CD4 T cells in 60-75 year olds. Sustained upregulation of zinc-binding metallothioneins after stimulation for longer period than they are upregulated for in young adults.

"Over-Expression of Heat Shock Protein 70 in Mice Is Associated with Growth Retardation, Tumor Formation, and Early Death" by Valerie Vanhooren, Xue-En Liu, Liesbeth Desmyter, Ye-Dong Fan, Lieve Vanwalleghem, Wim Van Molle, Sylviane Dewaele, Marleen Praet, Roland Contreras, Claude Libert, and Cuiying Chen. Mice genetically modified to overexpress HSP70 have lower weight (growth retardation), 50% lower concentrations of IGF-1, lower expression of glucocorticoid receptors in their livers and caspase-9 expression, higher levels of corticosterone and Bcl-2 expression (anti-apoptotic). I'd have thought most of these would have been good for lifespan, but no, they die at 18 months from tumours. Interesting. Paper is available.

"Enhanced Recovery from Contraction-Induced Damage in Skeletal Muscles of Old Mice Following Treatment with the Heat Shock Protein Inducer 17-(Allylamino)-17-Demethoxygeldanamycin" by Anna C. Kayani, Graeme L. Close, Caroline S. Broome, Malcolm J. Jackson, and Anne McArdle. Better recovery from exercise-induced damage to muscle in old mice when given a HSP70-inducer (84% vs 48% of pre-damage contractile force at 28 days). HSP70 bit over 2x higher. Full article available.

"Effect of Aging on Brain-Derived Neurotrophic Factor, proBDNF, and Their Receptors in the Hippocampus of Lou/C Rats" by M. Silhol, S. Arancibia, D. Perrin, T. Maurice, J. Alliot, and L. Tapia-Arancibia. Lou/C rats have better memory capacity than Wistar rats when old. Transcriptional analysis shows higher proBDNF in Lou/C, but decreased with age in contrast with Wistar. Also, lower decrease in TrkB.FL (proBDNF receptor), and no change in other proBDNF receptors in contrast with increases in Wistar.

"Weight Increase Is Associated with Skeletal Muscle Immunostaining for Advanced Glycation End Products, Receptor for Advanced Glycation End Products, and Oxidation Injury" by Maria Pia de la Maza, Jaime Uribarri, Daniela Olivares, Sandra Hirsch, Laura Leiva, Gladys Barrera, and Daniel Bunout. Immunostaining of caboxymethyl-lysine (CML, an AGE), and receptors of AGE (RAGE) from tissue taken from 10 middle-aged non-weight-gainers, 7 weight-gainers and 4 old people. CML and RAGE vs weight and age at r=0.84 (dunno how they combined the two).

"Engineered Repeated Electromagnetic Field Shock Therapy for Cellular Senescence and Age-Related Diseases" by Felipe P. Perez, Ximing Zhou, Jorge Morisaki, John Ilie, Todd James, and Donald A. Jurivich. They shock cells (?) and that upregulates HSR/HSF1 pathway. Temporarily reverses senescence and delays it in young cells.

de Grey's commentary on a thesis series topic: part of the differentiation mechanism from hESCs to mature neurons.

Issue 5, 2008

Switched to six issues per year in 2008.

This issue was wasted on me due to me not knowing even the basics about the immune system.

By the abstracts:

"Aluminum Modulates Effects of βAmyloid1–42 on Neuronal Calcium Homeostasis and Mitochondria Functioning and Is Altered in a Triple Transgenic Mouse Model of Alzheimer's Disease" by Denise Drago, Alessandra Cavaliere, Nicola Mascetra, Domenico Ciavardelli, Carmine Di Ilio, Paolo Zatta, and Stefano L. Sensi. What the title says. By altered, they mean increased in their cortex.

"Aging and Neutrophils: There Is Still Much To Do" by Carl F. Fortin, Patrick P. McDonald, Olivier Lesur, and Tàmàs Fülöp, Jr. Hypothesises about how aging affects the release of immune mediators by neutrophils, and how that links with Alzheimer's, atherosclerosis, cancer and autoimmune diseases.

"Differential Expression of Lysyl Oxidases LOXL1 and LOX During Growth and Aging Suggests Specific Roles in Elastin and Collagen Fiber Remodeling in Rat Aorta" by Jacques Behmoaras, Séverin Slove, Sophie Seve, Roger Vranckx, Pascal Sommer, and Marie-Paule Jacob. LOX goes down in adult rats while LOXL1 was maintained in LOU rats, but reduced in Brown Norway rats.

"Blueberry Opposes β-Amyloid Peptide-Induced Microglial Activation Via Inhibition of p44/42 Mitogen-Activation Protein Kinase" by Yuyan Zhu, Paula C. Bickford, Paul Sanberg, Brian Giunta, and Jun Tan. What the title says, in mice.

"Age-Dependent Spatial Memory Loss Can Be Partially Restored by Immune Activation" by N. Ron-Harel, Y. Segev, G.M. Lewitus, M. Cardon, Y. Ziv, D. Netanely, J. Jacob-Hirsch, N. Amariglio, G. Rechavi, E. Domany, and M. Schwartz. Hammering immune system fucks up spatial memory in young mice and homeostatic-driven proliferation (dunno what that phrase means. They removed some of their T-cells to let it expand its other types of T-cells?) of lymphocytes in old mice restores their spatial memory. Igf1, Syt10 and Cplx2 genes involed.

"Extensive Amplification of Human Regulatory T Cells Alters Their Functional Capacities and Targets Them to the Periphery" by Gunter Rappl, Annette Schmidt, Cornelia Mauch, Andreas A. Hombach, and Hinrich Abken. Details of Treg-cell life cycle for which I have nothing to grab onto.

"Melatonin Prevents Age-Related Mitochondrial Dysfunction in Rat Brain Via Cardiolipin Protection" by Giuseppe Petrosillo, Patrizia Fattoretti, Mariagiuseppa Matera, Francesca M. Ruggiero, Carlo Bertoni-Freddari, and Giuseppe Paradies. Melatonin prevented the age-related changes in complex 1 activity, rates of state 3 respiration (ADP-stimulated respiration google says), mitochondrion H2O2 production, membrane potential, and normal and oxidised cardiolipin content of mitochondria in rat brains.

"Improvement of Aging-Associated Cardiovascular Dysfunction by the Orally Administered Copper(II)-Aspirinate Complex" by Tamás Radovits, Domokos Gerö, Li-ni Lin, Sivakkanan Loganathan, Torsten Hoppe-Tichy, Csaba Szabó, Matthias Karck, Hiromu Sakurai, and Gábor Szabó. Some measurements of heart function across age in rats and their partial prevention by copper(II)-aspirinate.

"Effect of Lactobacillus paracasei NCC2461 on Antigen-Specific T-Cell Mediated Immune Responses in Aged Mice" by Karine Vidal, Jalil Benyacoub, Mireille Moser, J. Sanchez-Garcia, Patrick Serrant, Iris Segura-Roggero, Gloria Reuteler, and Stephanie Blum. No measurements of immune system components changed, but response increased. FOS/inulin made no difference.

The thesis-review section looks (at least) at a study of the growth and use of cardiac progenitor cells extracted from adult humans, grown into cardiosphere-derived cells, then inserted into mice with induced myocardial infarctions and seeing how they went. They supposedly did better than other types of cells  in maintaining left ventricular function and reducing left ventricular remodelling.

Issue 4, 2008

By the abstracts:

"Exercise-Induced Activation of STAT3 Signaling Is Increased with Age" by Marissa K. Trenerry, Kate A. Carey, Alister C. Ward, Michelle M. Farnfield, and David Cameron-Smith. STAT3 gets massively pumped in old people following exercise, more than young people (11 20-year olds vs 10 67-year olds). Downstream mRNA also pumped, but SOCS3 protein suppressed. This might mean something to people more familiar with those genes. They say it might impact muscle repair and regeneration.

"Deficiency of Insulin-Like Growth Factor 1 Reduces Sensitivity to Aging-Associated Cardiomyocyte Dysfunction" by Qun Li, Asli F. Ceylan-Isik, Ji Li, and Jun Ren. Whole bunch of physiological and gene expression changes to hearts in old mice. Mice with liver IGF-1 deficiency had attenuated changes. They also had lower FOXO3a expression and were glucose intolerant, same effects as aging.

"Identifying the Genes and Genetic Interrelationships Underlying the Impact of Calorie Restriction on Maximum Lifespan: An Artificial Intelligence-Based Approach" by Ben Goertzel, Cassio Pennachin, Maurício de Alvarenga Mudado, and Lúcio de Souza Coelho. Analysis of three mouse CR studies and validated on a fourth suggest that Mrpl12, Uqcrh and Snip1 are important to the effects of CR on life extension.

"Host Cell Mobilization for In Situ Tissue Regeneration" by Sang Jin Lee, Mark Van Dyke, Anthony Atala, and James J. Yoo. Measurements of host cells infiltrations in common biomaterial put into mice: not altogether inflammatory. Infiltrating cells can differentiate into osteogenic, myogenic, adipogenic and endothelial lineages, given the correct conditions.

"Identifying the Changes in Gene Profiles Regulating the Amelioration of Age-Related Oxidative Damages in Kidney Tissue of Rats by the Intervention of Adult-Onset Calorie Restriction" by Jie Chen, Chidambaram Natesa Velalar, and Runsheng Ruan. 1-year old rats. CR decreased lipid peroxidation and protein oxidation in kidneys, maybe from a drop in plasminogen activation inhibition-1 and clusterin, and increase of kallikrein mRNA. Inflammatory response down. Fatty acid synthesis, mitochondrial fatty acid beatoxidation, glycolysis and gluconeogenesis up. All in kidneys, and CR as compared with controls.

"Cryopreservation of Whole Murine and Porcine Livers" by Zohar Gavish, Menachem Ben-Haim, and Amir Arav. Frozen rat and pig livers, dunno for how long or at what temperature. Thawed and transplanted in, produced bile and had blood flow. They say 80% viability. Used "directional solidification apparatus". Hadn't heard of this result, sounds useful.

"Preliminary Evidence that VEGF Genetic Variability Confers Susceptibility to Frontotemporal Lobar Degeneration" by B. Borroni, S. Ghezzi, C. Agosti, S. Archetti, C. Fenoglio, D. Galimberti, E. Scarpini, M. Di Luca, N. Bresolin, G.P. Comi, A. Padovani, and R. Del Bo. 30-50% of FTLD have positive family history. This study compared 216 controls with 161 FTLDs, finds differences distribution of SNPs in VEGF gene promoter region.

"Lysophosphatidic Acid and Adenylyl Cyclase Inhibitor Increase Proliferation of Senescent Human Diploid Fibroblasts by Inhibiting Adenosine Monophosphate-Activated Protein Kinase" by Ji-Heon Rhim, Ik-Soon Jang, Kye-Yong Song, Moon-Kyung Ha, Sung-Chun Cho, Eui-Ju Yeo, and Sang Chul Park. What the title says through inhibition of the catalytic activity of AMPKalpha and p53.

"Long-Term Effects of Caloric Restriction or Exercise on DNA and RNA Oxidation Levels in White Blood Cells and Urine in Humans" by Tim Hofer, Luigi Fontana, Stephen D. Anton, Edward P. Weiss, Dennis Villareal, Bhaskar Malayappan, and Christiaan Leeuwenburgh. 9 50something year olds on 20% CR and 9 50something year olds on 20% (energy deficity through) exercise. After a year, big drop in DNA and RNA oxidation in white blood cells but no changes in either in urine.

"Aging, Stem Cells, and Mammalian Target of Rapamycin: A Prospect of Pharmacologic Rejuvenation of Aging Stem Cells" by Mikhail V. Blagosklonny. Hypothesises that insensitivity of stem cells to activating stimuli is partly due to hyperactivation of TOR, so suggests rapamycin would rejuvenate stem cells. Wouldn't mind seeing his reasoning/evidence.

"Clinical Outcome and Mechanism of Soft Tissue Calcification in Werner Syndrome" by Satoshi Honjo, Koutaro Yokote, Masaki Fujimoto, Minoru Takemoto, Kazuki Kobayashi, Yoshiro Maezawa, Tatsushi Shimoyama, Seiya Satoh, Masaya Koshizaka, Aki Takada, Hiroki Irisuna, and Yasushi Saito. WS people have calcifications in the skin near joints, probably produced by overexpression of Pit-1.

"Carnisone Increases Efficiency of DOPA Therapy of Parkinson's Disease: A Pilot Study" by Alexander Boldyrev, Tatiana Fedorova, Maria Stepanova, Irina Dobrotvorskaya, Eugenia Kozlova, Natalia Boldanova, Gulbakhar Bagyeva, Irina Ivanova-Smolenskaya, and Serguey Illarioshkin. From the abstract, it seems like it was meant to say carnosine. Added to standard treatment for Parkinson's, seemed to do better.

"Comparative Value of Medical Diagnosis Versus Physical Functioning in Predicting the 6-Year Survival of 1951 Hospitalized Old Patients" by Emilia Frangos Lordos, François R. Herrmann, Jean-Marie Robine, Mireille Balahoczky, Sandra V. Giannelli, Gabriel Gold, and Jean-Pierre Michel. First page available instead of the abstract. 6-year study. First page doesn't get to the numbers but says that functional status is most important. Sounds like a good one.

The first thesis reviewed is called "Unravelling Tissue Regeneration Using Chemical Genetics" by Lijoy Mathew. Seems to be a study of some of the mechanisms of inhibition of regeneration of the zebrafish caudal fin. Glucocorticoids inhibit is all I understood.

Issue 3, 2008

By the abstracts:

"CD7− T Cells are Late Memory Cells Generated from CD7+ T Cells" by Gunter Rappl, David Schrama, Andreas Hombach, Eva Katharina Meuer, Annette Schmidt, Jürgen C. Becker, and Hinrich Abken. Details of immune system about which I understand practically nothing. For the record, they say CD7- cells are T cells in late memory cell development, have a high activation threshold, low effector capacities and high sensitivity to activation-induced cell death.

"Carotenoids as Protection Against Disability in Older Persons" by Fulvio Lauretani, Richard D. Semba, Stefania Bandinelli, Margaret Dayhoff-Brannigan, Fabrizio Lauretani, Anna Maria Corsi, Jack M. Guralnik, and Luigi Ferrucci. Measured plasma carotenoids in 928 >65 year olds, as supposed proxy of fruit and vegetable intake. Higher carotenoid correlated with higher walking speed at original measurement, higher speed at remeasurement 6 years later and lower likelihood of becoming unable to walk (all the odd ratios around 0.5).

"Altered Expression of Mismatch Repair Proteins Associated with Acquisition of Microsatellite Instability in a Clonal Model of Human T Lymphocyte Aging" by Simona Neri, Graham Pawelec, Andrea Facchini, Cinzia Ferrari, and Erminia Mariani. T-cell clones in vitro that develop microsatellite instability have disregulated expression of mismatch repair proteins. Those that don't don't.

"Homeostatic Cytokines and Expansion of Regulatory T Cells Accompany Thymic Impairment in Children with Down Syndrome" by Erika Roat, Nicole Prada, Enrico Lugli, Milena Nasi, Roberta Ferraresi, Leonarda Troiano, Chiara Giovenzana, Marcello Pinti, Ornella Biagioni, Mauro Mariotti, Angelo Di Iorio, Ugo Consolo, Fiorella Balli, and Andrea Cossarizza. Kids with Down syndrome have very different immunological profiles from control kids.

"Brain Magnetic Resonance Imaging Structural Changes in a Pedigree of Asymptomatic Progranulin Mutation Carriers" by B. Borroni, A. Alberici, E. Premi, S. Archetti, V. Garibotto, C. Agosti, R. Gasparotti, M. Di Luca, D. Perani, and A. Padovani. Measurements of differences and non-differences in brain areas between controls, asymptomatic carriers of progranulin mutations with family history of frontotemporal lobar degeneration and people with family history of FTLD but no progranulin mutation.

"Caloric Restriction Retards the Age-Related Decline in Mitochondrial Function of Brown Adipose Tissue" by Adamo Valle, Rocío Guevara, Francisco José García-Palmer, Pilar Roca, and Jordi Oliver. The english in this one isn't very clear: they compared 2-year old 40% CR rats with 2-year old and 6-month old controls: lower brown adipose tissue (BAT) "size with respect to fat content and adipocyte number" (ratio?). Higher mtDNA content in CR > old control > young control. CR BAT slowed decline of total and mt protein, COX activity and uncoupling capacity. They think CR prevents decline in mt function, probably due to lower decline in mt biogenesis.

"Caloric Restriction But Not Exercise-Induced Reductions in Fat Mass Decrease Plasma Triiodothyronine Concentrations: A Randomized Controlled Trial" by Edward P. Weiss, Dennis T. Villareal, Susan B. Racette, Karen Steger-May, Bhartur N. Premachandra, Samuel Klein, and Luigi Fontana. What the title says. 18 CR, 17 exercise, 9 controls. 50-60 year olds. No change in TSH, T4 and FT4. Decent weight changes in CR and exercise.

"Mitochondrial DNA Mutations May Contribute to Aging Via Cell Death Caused by Peptides that Induce Cytochrome c Release" by Steven J. Dubec, Rajeev Aurora, and H. Peter Zassenhaus. Biochemical evidence saying that mtDNA mutations generate a peptide that causes release of cytochrome c. Simulations from that to age-related mtDNA mutations causing significant levels of cell death. Also, mice with shitty proofreading version of poly gamma in the heart develop cardiomyopathy.

"Effect of Every Other Day Feeding on Mitochondrial Free Radical Production and Oxidative Stress in Mouse Liver" by Pilar Caro, José Gómez, Mónica López-Torres, Inés Sánchez, Alba Naudi, Manuel Portero-Otín, Reinald Pamplona, and Gustavo Barja. EOD feeding of mice lowered free radical leakeage from complex 1 but not complex 3 of liver mt. Also lowered mtDNA oxidative marker, protein oxidation, glycoxidation and lipoxidation, apoptosis inducing factor, PGC1-alpha and UCP2.

"Ketogenic Diets Cause Opposing Changes in Synaptic Morphology in CA1 Hippocampus and Dentate Gyrus of Late-Adult Rats" by Marta Balietti, Belinda Giorgetti, Patrizia Fattoretti, Yessica Grossi, Giuseppina Di Stefano, Tiziana Casoli, Daniela Platano, Moreno Solazzi, Fiorenza Orlando, Giorgio Aicardi, and Carlo Bertoni-Freddari. Brain stuff. Bad effects from fat-producing diets in hippocampal CA1, good in dentate gyrus. In mice.

"Creatine Supplementation Augments Skeletal Muscle Carnosine Content in Senescence-Accelerated Mice (SAMP8)" by Wim Derave, Glenys Jones, Peter Hespel, and Roger C. Harris. Accelerated-aging mice had drops in muscle content of carnosine, anserine, taurine and total creatine. Creatine supplementation raised it compared to controls while young but not when old.

"Regulating the Age-Related Oxidative Damage, Mitochondrial Integrity, and Antioxidative Enzyme Activity in Fischer 344 Rats by Supplementation of the Antioxidant Epigallocatechin-3-Gallate" by Qingying Meng, Chidambaram Natesa Velalar, and Runsheng Ruan. Epigallocatechin-3-Gallate aka EGCG is the main catechin in tea. High EGCG doses had lower DNA-oxidation marker and better mt potential in lymphocytes and lower deletion of ND4 region in mtDNA in the liver. In rats.

"L-Cysteine Influx in Erythrocytes as a Function of Human Age" by Syed Ibrahim Rizvi and Pawan Kumar Maurya. Red-blood cells from old people suspended in L-cysteine solution absorb less L-cysteine than red blood cells from young people.


Some leftovers from SENS3 that probably didn't fit in the previous issue:

"Genetic Susceptibility Sets for Alzheimer's Disease Identified from Diverse Candidate Loci" by Elizabeth H. Corder, Kaj Blennow, and Jonathan A. Prince. Fancy statistical analysis of GWAS plus physiological measures for detecting sets of features that lead to high risk of AD. 938 AD patients and 397 controls. Sounds interesting, need to understand details.

"Senescence Induces a Proangiogenic Switch in Human Peritoneal Mesothelial Cells" by Krzysztof Ksiazek, Achim Jörres, and Janusz Witowski. What the title says. They think this is why cancers metastise to the peritoneum when old.


Commentaries:

"On Methionine Restriction, Suppression of Mitochondrial Dysfunction and Aging" by Alan R. Hipkiss. Gives possible mechanisms by which methionine restriction might be beneficial: lower protein synthesis leading to lower mutant proteins. Ligher work for proteases so they can deal with post-translational problems. Alteration of protein folding (how?), increased lysosomal proteolysis, autophagy of mt and mitogenesis. May decrease SAM => decrease in O6-methylguanine, also might affect gene silencing.

A look at a thesis by Tamuna Chadashvili that looks at neural stem cell generation in rats. Seems to have found another region of generation aside from measuring a whole bunch of correlates with generation.

Issue 2, 2008

This seems to be the SENS-3 conference proceedings report. Very few interesting ones.

By the abstracts, and by the sections they are under:

Cardiovascular disease

"Age-Specific Modulation of Genes Involved in Lipid and Cholesterol Homeostasis by Dietary Zinc" by Dawn J. Mazzatti, Eugenio Mocchegiani, and Jonathan R. Powell. The abstract doesn't say any more than the title.

"Modulation of Genes Involved in Zinc Homeostasis in Old Low-Grade Atherosclerotic Patients Under Effects of HMG-CoA Reductase Inhibitors" by Laura Costarelli, Elisa Muti, Marco Malavolta, Robertina Giacconi, Catia Cipriano, Davide Sartini, Monica Emanuelli, Mauro Silvestrini, Leandro Provinciali, Beatrice Gobbi, and Eugenio Mocchegiani. Beyond me. Something about zinc signalling in specific immune cells.

"TLR2 and Age-Related Diseases: Potential Effects of Arg753Gln and Arg677Trp Polymorphisms in Acute Myocardial Infarction" by Carmela Rita Balistreri, Guiseppina Candore, Monica Mirabile, Domenico Lio, Gregorio Caimi, Egle Incalcaterra, Marco Caruso, Enrico Hoffmann, and Calogero Caruso. No association between those two polymorphisms and MI.

"A Novel Zip2 Gln/Arg/Leu Codon 2 Polymorphism Is Associated with Carotid Artery Disease in Aging" by Robertina Giacconi, Elisa Muti, Marco Malavolta, Maurizio Cardelli, Sara Pierpaoli, Catia Cipriano, Laura Costarelli, Silvia Tesei, Vittorio Saba, and Eugenio Mocchegiani. Patients with carotid stenosis have more GG and less TT in codon 2 of the hZIP2 gene than controls.

Neurodegeneration

"DNA Vaccine Therapy for Alzheimer's Disease: Present Status and Future Direction" by Yoshio Okura and Yoh Matsumoto. Review of vaccine therapies for Alzheimer's and positive data about non-viral DNA vaccine experiments on mice.

"Decreased Presence of Perforated Synapses in a Triple-Transgenic Mouse Model of Alzheimer's Disease" by Carlo Bertoni-Freddari, Stefano L. Sensi, Belinda Giorgetti, Marta Balietti, Giuseppina Di Stefano, Lorella M.T. Canzoniero, Tiziana Casoli, and Patrizia Fattoretti. Comparison of the brains of an Alzheimer's mouse model with controls.

"An Ultrasensitive Assay for Diagnosis of Alzheimer's Disease" by Susanne Aileen Funke, Eva Birkmann, Franziska Henke, Philipp Görtz, Christian Lange-Asschenfeldt, Detlev Riesner, and Dieter Willbold. Test for amyloid beta using fluorescence correlation spectroscopy (no idea). Correlations between those measurements and clinical AD symptoms. (Did this become accepted? Sounds very useful)

"Alzheimer's Disease-Like Changes in Herpes Simplex Virus Type 1 Infected Cells: The Case for Antiviral Therapy" by Ruth F. Itzhaki and Matthew A. Wozniak. Investigates link between HSV1 infection in the brain and AD, with APOE variants acting as modulators, possibly due to competitive binding of HSV1 entry into cell.

"Cerebral Amyloid-Beta Protein Accumulation with Aging in Cotton-Top Tamarins: A Model of Early Alzheimer's Disease?" by Cynthia A. Lemere, Jiwon Oh, Heather A. Stanish, Ying Peng, Imelda Pepivani, Anne M. Fagan, Haruyasu Yamaguchi, Susan V. Westmoreland, and Keith G. Mansfield. Cotton-top tamarins have amyloid beta plaques.

"Long-Term Visual Object Recognition Memory in Aged Rats" by Daniela Platano, Patrizia Fattoretti, Marta Balietti, Carlo Bertoni-Freddari, and Giorgio Aicardi. They developed a long term (24 hours) memory test that old rats can perform. Supposedly, none was reported before. Interesting also that number of rat-turds is used as a measurement of anxiety.

"Synaptic Remodeling in Hippocampal CA1 Region of Aged Rats Correlates with Better Memory Performance in Passive Avoidance Test" by Daniela Platano, Patrizia Fattoretti, Marta Balietti, Belinda Giorgetti, Tiziana Casoli, Giuseppina Di Stefano, Carlo Bertoni-Freddari, and Giorgio Aicardi. Density of synapses and mitochondria was higher and mitochondrial volume was lower in the rat CA1 hippocampal region 9 hours compared to 6 hours after a memory training exercise in rats that learnt well.

"Immunological Approaches for Amyloid-beta Clearance Toward Treatment for Alzheimer's Disease" by Beka Solomon. Seems to be a review of vaccines against amyloid-beta, but hard to tell.

"A Highly Sensitive Diagnostic Assay for Aggregate-Related Diseases, Including Prion Diseases and Alzheimer's Disease" by Eva Birkmann, Franziska Henke, Susanne Aileen Funke, Oliver Bannach, Detlev Riesner, and Dieter Willbold. Another ultra-sensitive test of protein aggregates by the same group as the one above. This time using surface-fluorescence intensity distribution analysis (and again, no idea).

"Aggregation and Amyloid Fibril Formation of the Prion Protein Is Accelerated in the Presence of Glycogen" by Giannantonio Panza, Jan Stöhr, Eva Birkmann, Detlev Riesner, Dieter Willbold, Otto Baba, Tatsuo Terashima, and Christian Dumpitak. Prion and prion fibril formation is accelerated by the presence of glycogen.


Stem cells

"Characterizing Endothelial Cells Derived from the Murine Embryonic Stem Cell Line CCE" by Fardin Fathi, Abbas Jafari Kermani, Leila Pirmoradi, Seyed Javad Mowla, and Takayuki Asahara. Description of a process to generate endothelial cells from mice ESCs, and characterisation of the generated cells.

"Characterization and Genetic Manipulation of Human Umbilical Cord Vein Mesenchymal Stem Cells: Potential Application in Cell-Based Gene Therapy" by Abbas Jafari Kermani, Fardin Fathi, and Seyed Javad Mowla. Isolation and characterisation of gene expression and surface markers of human umbilical cord vein mesenchymal stem cells. They also electroporated green fluorescent protein and brain-derived neurotrophic factor genes in and got them expressed.


Mitochondria and Oxidative Damage

"Selective Decline of the Metabolic Competence of Oversized Synaptic Mitochondria in the Old Monkey Cerebellum" by Carlo Bertoni-Freddari, Marta Balietti, Belinda Giorgetti, Yessica Grossi, Tiziana Casoli, Giuseppina Di Stefano, Gemma Perretta, and Patrizia Fattoretti. Numeric density, volume density, average volume and average length of mitochondria in the cortex wasn't different between adult and old crab-eating macaques. What was different was the ratio of COX cytochemical precipitate to area of the mitochondrion, which declined, but only in large mitochondria. They take that ratio to be a proxy for mitochondrial metabolic competence.

"Oxidative Stress in Patients with Acute Heart Failure" by Jean-Christophe Charniot, Noëlle Vignat, Jean-Paul Albertini, Vera Bogdanova, Khaled Zerhouni, Jean-Jacques Monsuez, Alain Legrand, Jean-Yves Artigou, and Dominique Bonnefont-Rousselot. Ten people with dilated cardiomyopathy. Higher thiobarbituric acid-reactive substances (TBARS) and lower total antioxidant status (TAS), especially when they had arrythmias. Normal alpha-tocopherol, vitamin A and beta-carotene. TBARS and TAS returned to normal once patients returned to stable conditions.

"Anti-Inflammatory Senescence Actives 5203-L Molecule to Promote Healthy Aging and Prolongation of Lifespan" by Jean-François Bisson, Chantal Menut, and Patrizia d'Alessio. The monoterpene AISA 5203-L reverses replicative senescence of human vascular endothelial cells and mellows stress according to some tests. Focus seems to be on medium-stress inducing disease. Hippy vibe but maybe I'm misreading.

"Do Mitochondrial DNA and Metabolic Rate Complement Each Other in Determination of the Mammalian Maximum Longevity?" by Gilad Lehmann, Elena Segal, Khachik K. Muradian, and Vadim E. Fraifeld.  GC content of mtDNA together with resting metabolic rate can explain 77% of the variation in maximum lifespan in a study of 140 mammalian species. Maybe interesting.

"Zinc, Metallothioneins, Longevity: Effect of Zinc Supplementation on Antioxidant Response: A Zincage Study" by Eugenio Mocchegiani and The Zincage Consortium. Something about zinc, clusterin, PARP-1 MSR-A, methallothioneins and IL-6. Not sure what.


Immunosenescence

"Immunosenescence and Anti-Immunosenescence Therapies: The Case of Probiotics" by Giuseppina Candore, Carmela Rita Balistreri, Giuseppina Colonna-Romano, Maria Paola Grimaldi, Domenico Lio, Florinda Listi', Letizia Scola, Sonya Vasto, and Calogero Caruso. Possible strategies to defend against thymic involution, domination by memory T-cell and chronic inflammation through probiotics.

"B Cell Immunosenescence in the Elderly and in Centenarians" by Giuseppina Colonna-Romano, Matteo Bulati, Alessandra Aquino, Salvatore Vitello, Domenico Lio, Giuseppina Candore, and Calogero Caruso. B-cells in old people don't respond to new pathogens.


Intracellular Aggregates

"Can Lipofuscin Accumulation Be Prevented?" by Tino Kurz. Reducing intralysosomal iron reduces oxidative stress which could reduce lipofuscin formation. Wants to try pulse doses of iron chelators to see.

"Accumulating Insoluble Protein and Rate of Aging" by Anund Hallén. Thinks there's a link between the exponential form of the Gompertz law with the logarithmic space available to macromolecules in cells due to the formation of a polymer network in the cell which stops the macromolecules/colloids from moving through the cell.


Cell senescence

"Role of Insulin-Like Growth Factor Binding Protein-3 in Human Umbilical Vein Endothelial Cell Senescence" by Christoph Muck, Lucia Micutkova, Werner Zwerschke, and Pidder Jansen-Durr. IGFBP-3 transfection induces apoptosis and senescence in HUVEC. Knockdown by shRNA doesn't revert that.

"Metallothionein Downregulation in Very Old Age: A Phenomenon Associated with Cellular Senescence?" by Marco Malavolta, Catia Cipriano, Laura Costarelli, Robertina Giacconi, Silvia Tesei, Elisa Muti, Francesco Piacenza, Sara Pierpaoli, Annis Larbi, Graham Pawelec, George Dedoussis, George Herbein, Daniela Monti, Jolanta Jajte, Lothar Rink, and Eugenio Mocchegiani. MT proteins decrease in the very old, independent of zinc intake. Age-dependent zinc changes also happen in CD4+ T cells in vitro and peripheral blood mononuclear cells ex-vivo. They follow this with a "thus" old age problems might be partially attributable to diminished cell proliferation, implying that the above is related to cell proliferation.

"Repeat Mild Heat Shock Increases Dermal Fibroblast Activity and Collagen Production" by Andrew E. Mayes and Caroline D. Holyoak. What the title says, in cells from a 12, 22 and 65 year olds.


Nutrient Sensing

"Relationship Between Calorie Restriction and the Biological Clock: Lessons from Long-Lived Transgenic Mice" by Oren Froy, Nava Chapnik, and Ruth Miskin. alpha-MUPA mice eat 20% less and live 20% longer. They have high amplitude, appropriately reset circadian rhythms in clock gene expression, and circadian behaviours. (I'm not sure what that means. That the sun resets the gene expression rhythm quickly?) They say that since CR resets circadian rhythm, maybe that's a mediator of the longevity extension.

"Enhancing Longevity: Novel Caloric Restriction Mimetics" by Alexander E. Michalow. No abstract. First page didn't get to the point.


Psychological, Political, and Social Context

"Zinc in Elderly People: Effects of Zinc Supplementation on Psychological Dimensions in Dependence of IL-6 -174 Polymorphism: A Zincage Study" by Fiorella Marcellini, Cinzia Giuli, Roberta Papa, Cristina Gagliardi, George Dedoussis, Daniela Monti, Jolanta Jajte, Robertina Giacconi, Marco Malavolta, and Eugenio Mocchegiani. Looked at zinc intake combined with 174-polymorphism in IL-6 in old people. Improved perceived stress but not results of mini-mental state examination or geriatric depression scale.

"Making the Political Case for Biogerontology Funding: A View from the Trenches" by Huber R. Warner.  Funding.


General

"Have We Reached the Point for In Vivo Rejuvenation?" by Amir Abramovich, Khachik K. Muradian, and Vadim E. Fraifeld. Wants to try de-differentiation and re-differentiation in vivo. Hints at iPSCs. Was waiting for this to pop up.

"Scientific Justification of Cryonics Practice" by Benjamin P. Best. Open access but not reading. I suspect I'm familiar with the arguments, don't need to be convinced.

"Youth Maintenance and Postponing Human Aging in Reality" by Ülo Kristjuhan. Nothing concrete in abstract (not intended), but vaguely how to accelerate the life extension currently happening.

"Role of Environmental and Genetic Factor Interaction in Age-Related Disease Development: The Gastric Cancer Paradigm" by Giusi Irma Forte, Cinzia Calà, Letizia Scola, Antonino Crivello, Arianna Gullo, Lorenzo Marasà, Antonio Giacalone, Celestino Bonura, Calogero Caruso, Domenico Lio, and Anna Giammanco. The 511T-variant of IL-1 beta is associated with an increased risk of chronic gastritis.

'“Accelerating Aging” Chemotherapy on Aged Animals: Protective Effect from Nutraceutical Modulation' by Francesco Marotta, Masatoshi Harada, Emilio Minelli, Suzanne K. Ono-Nita, and Paulo Marandola. Denshichi-Tochiu-Sen recovered macrophage chemotaxis, function and concentration and some other things on mice given chemotherapy.

"Muscular Metabolism in Aged Rats Under Exhaustive Exercise: Effect of a Modified Alkaline Supplementation" by Francesco Marotta, De Hua Chui, Aldo Lorenzetti, Flavia Fayet, Tsin Liu, and Paolo Marandola. They added modified alkalizing supplementation (MAS) to some rats running them to exhaustion. Exercise increased lactic acid and creatin-phosphokinase, and dropped muscle glycogen. MAS group had bigger succinate dehydrogenase and acetylcarinitine increases.

"Genetic Polymorphisms and Human Aging: Association Studies Deliver" by David Melzer. GWAS found polymorphisms in INK4a/INK4b and CDKN2a/b genes in p16/p15 locus linked with differences in physical function in old people. Later GWAS studying type 2 diabetes and MI confirms importance of this locus.

"Making SENSE: Strategies for Engineering Negligible Senescence Evolutionarily" by Michael R. Rose. Treat aging through evolutionary means. Rose-ish content.

Issue 1, 2008

By the abstracts:

"Human Embryonic Stem Cell Telomere Length Impacts Directly on Clonal Progenitor Isolation Frequency" by Nicholas R. Forsyth and Jim McWhir. They identify and grab some partially differentiated hESCs that divide a lot and count how many times they can divide. They measure the length of the telomeres of the parent hESCs and say that the number of times that the offspring divided matches the telomere-bound limit. They also insert hTERT and I think they are saying that the offspring can then replicate forever but I'm not clear about this. Did this end up being true? Sounds pretty good if it did.

"Embryonic Stem Cells: From Markers to Market" by Kaushik Dilip Deb, Anitha Devi Jayaprakash, Vijay Sharma, and Satish Totey. Review paper about safety epigenetic markers, stemness gene-expression markers and lineage gene-expression markers in hESCs.

"Epigenetic Engineering and Its Possible Role in Anti-Aging Intervention" by Alexander M. Vaiserman. Hypothesises that the hormetic effect on lifespan might come about through a common epigenetic mechanism regardless of the type of stressor. Seems to be talking about early-life mild stressors only.

"Long-Term Treatment with a Yang-Invigorating Chinese Herbal Formula Produces Generalized Tissue Protection Against Oxidative Damage in Rats" by Po Yee Chiu, Hoi Yan Leung, Ada Hoi Ling Siu, Na Chen, Michel K.T. Poon, and Kam Ming Ko. Spruiking Vigconic 28. Tested on female rats, claims to have increased copper-zinc superoxide dismutase levels and general oxidant damage resistance in tissue and mitochondria.

"Fatty Acid Profile of Erythrocyte Membranes As Possible Biomarker of Longevity" by Annibale A. Puca, Peter Andrew, Valeria Novelli, Chiara Viviani Anselmi, Francesco Somalvico, Nicola A. Cirillo, Chryssostomos Chatgilialoglu, and Carla Ferreri. 90-something year olds have more monounsaturated and less long polyunsaturated fatty acids in their red blood cells.

"Immunoproteasome in Macaca fascicularis: No Age-Dependent Modification of Abundance and Activity in the Brain and Insight into an in silico Structural Model" by Elena Bellavista, Michele Mishto, Aurelia Santoro, Carlo Bertoni-Freddari, Richard B. Sessions, and Claudio Franceschi. Not really sure. They find no difference in activity of these proteasome proteins in young and old in different parts of the brains of crab-eating macaques, except in one area. They also built a model of something, but it's all beyond me.

"Lifelong α-Tocopherol Supplementation Increases the Median Life Span of C57BL/6 Mice in the Cold but Has Only Minor Effects on Oxidative Damage" by Colin Selman, Jane S. McLaren, Claus Mayer, Jackie S. Duncan, Andrew R. Collins, Garry G. Duthie, Paula Redman, and John R. Speakman. What the title says. Cold means 7 degrees. 785 days vs 682 days. 44 in each group.

"Elastin Haploinsufficiency Induces Alternative Aging Processes in the Aorta" by Mylène Pezet, Marie-Paule Jacob, Brigitte Escoubet, Dealba Gheduzzi, Emmanuelle Tillet, Pascale Perret, Philippe Huber, Daniela Quaglino, Roger Vranckx, Dean Y. Li, Barry Starcher, Walter A. Boyle, Robert P. Mecham, and Gilles Faury.  Elastin is synthesised only in early life (!). Mice (+/-) on Eln had same lifespan, but looked like they had vascular issues early, typical of stiff arteries, but didn't have the issues later with arterial wall thickening and alpha-1-adrenoceptor-mediated vasoconstriction.

"Paraoxonase 1: Genetics and Activities During Aging" by Francesca Marchegiani, Maurizio Marra, Fabiola Olivieri, Maurizio Cardelli, Richard W. James, Massimo Boemi, and Claudio Franceschi. Paroxonase-1 is an enzyme that protects lipids from peroxidative damage. This is a review of its possible effects on human longevity.

"Hypermagnesemia Predicts Mortality in Elderly with Congestive Heart Disease: Relationship with Laxative and Antacid Use" by Graziamaria Corbi, Domenico Acanfora, Gian Luca Iannuzzi, Giancarlo Longobardi, Francesco Cacciatore, Giuseppe Furgi, Amelia Filippelli, Giuseppe Rengo, Dario Leosco, and Nicola Ferrara. 3-year survival of 17.3 vs 22.5 months of hypermagnesia vs normomagnesia in 200 CHF >65 year old patients. Other measurements too.

"Exercise Training Promotes SIRT1 Activity in Aged Rats" by Nicola Ferrara, Barbara Rinaldi, Graziamaria Corbi, Valeria Conti, Paola Stiuso, Silvia Boccuti, Giuseppe Rengo, Francesco Rossi, and Amelia Filippelli. Lot of cites of this one for some reason. Aging reduced SIRT1 activity in the heart but not in the fat. Decreased MnSOD and catalase in both. Increased oxidation markers in both. Exercised old rats had higher MnSOD and catalase in both. Increased FOXO3a protein in the heart and mRNA in the fat. Increased SIRT1 in the heart.

"Development and Validation of a Multidimensional Prognostic Index for One-Year Mortality from Comprehensive Geriatric Assessment in Hospitalized Older Patients" by Alberto Pilotto, Luigi Ferrucci, Marilisa Franceschi, Luigi P. D'Ambrosio, Carlo Scarcelli, Leandro Cascavilla, Francesco Paris, Giuliana Placentino, Davide Seripa, Bruno Dallapiccola, and Gioacchino Leandro. Also a crapload of cites. 63-variable classifier with a 0.751 ROC on 6-month and 1-year mortality. 850 people in each of the training and validation set.

"Human Sarcopenia Reveals an Increase in SOCS-3 and Myostatin and a Reduced Efficiency of Akt Phosphorylation" by Bertrand Léger, Wim Derave, Katrien De Bock, Peter Hespel, and Aaron P. Russell. Tons of cites. Fast-muscle cross-sectional fibre area 45% lower in 70-year olds compared to 20-year olds. Higher myostatin, TNF-alpha, SOCS-3, total, but not phosphorilated, Akt, GSK-3beta. Lower growth hormone reeptor and IGF-1 mRNA.

"Effect of Senescence on Macrophage Polarization and Angiogenesis" by Dru S. Dace and Rajendra S. Apte. Review of age-related changes in innate immune system, especially macrophages and eye disease.

"Response to Histamine Allows the Functional Identification of Neuronal Progenitors, Neurons, Astrocytes, and Immature Cells in Subventricular Zone Cell Cultures" by Fabienne Agasse, Liliana Bernardino, Bruno Silva, Raquel Ferreira, Sofia Grade, and João O. Malva. A brain one. I suck at brain ones. They distinguish type of neurons by grabbing one and pumping histamine or potassium chloride on it and seeing how their calcium-ion levels changed.

"Dietary Supplementation Exerts Neuroprotective Effects in Ischemic Stroke Model" by Takao Yasuhara, Koichi Hara, Mina Maki, Tadashi Masuda, Cyndy D. Sanberg, Paul R. Sanberg, Paula C. Bickford, and Cesar V. Borlongan. Gave rats blueberry, green tea, vitamin D3 and carnosine, then gave them a stroke. Treated rats did better. 8 rats per group.

"Tonic β-Adrenergic Drive Provokes Proinflammatory and Proapoptotic Changes in Aging Mouse Heart" by Aihua Hu, Xiangying Jiao, Erhe Gao, Yonghai Li, Said Sharifi-Azad, Zvi Grunwald, Xin L. Ma, and Jian-Zhong Sun. Older mice had higher inducible nitric oxide synthase, CRP and myocardial apoptosis. Can generate those same issues in young mice by pumping isoproterenol, a beta-adrenergic receptor stimulator.

"Zinc Supplementation in the Elderly Reduces Spontaneous Inflammatory Cytokine Release and Restores T Cell Functions" by Laura Kahmann, Peter Uciechowski, Sabine Warmuth, Birgit Plümäkers, Axel M. Gressner, Marco Malavolta, Eugenio Mocchegiani, and Lothar Rink. Zinced up 19 old people. Cytokine release went down, and something else, claiming lower inflamation but better immune response.

"Cognitive Training Is Ineffective in Hypoxemic COPD: A Six-Month Randomized Controlled Trial" by Raffaele Antonelli Incalzi, Andrea Corsonello, Luigi Trojano, Claudio Pedone, Domenico Acanfora, Aldo Spada, Orsola Izzo, and Franco Rengo. Cognitive training plus standard care did no better than standard care for people with COPD on cognitive performance at 6 months. 50 people per group. Negative results always sound more believable.

"An Inverse Association Between Self-Reported Arthritis and Mortality in the Elderly: Findings from the National Long-Term Care Survey" by Alexander M. Kulminski, Irina V. Kulminskaya, Svetlana V. Ukraintseva, Kenneth Land, and Anatoli I. Yashin. Strange one: people who reported to have arthritis lived longer. Relative risk 0.81. Result of fishing?

Issue 4, 2007

By the abstracts:

"Effect of Short-Term Ketogenic Diet on Redox Status of Human Blood" by Rafal R. Nazarewicz, Wieslaw Ziolkowski, Patrick S. Vaccaro, and Pedram Ghafourifar. Giving twenty thin women a low calorie, high fat diet for two weeks raised their blood antioxidative capacity.

"Lipoproteins, Vascular-Related Genetic Factors, and Human Longevity" by Francesco Panza, Alessia D'introno, Cristiano Capurso, Anna Maria Colacicco, Davide Seripa, Alberto Pilotto, Andrea Santamato, Antonio Capurso, and Vincenzo Solfrizzi. Reports about different proportions of lots of diferent alleles in centenarians compared with the rest of the population.

"Intrinsic and Microenvironmental Defects Are Involved in the Age-Related Changes of Lin−c-kit+ Hematopoietic Progenitor Cells" by Alessia Donnini, Francesca Re, Fiorenza Orlando, and Mauro Provinciali. There are less of these specific type of lymphocyte stem cells in old than in young mice. When you transplant these cells from young and old mice into young mice, the ones from young mice differentiate more efficiently, even if you transplant a young thymus along for the ride. When these type of cells from young mice are transplanted into young or old mice, they do better when transplanted into young mice.

"Methionine Restriction Decreases Endogenous Oxidative Molecular Damage and Increases Mitochondrial Biogenesis and Uncoupling Protein 4 in Rat Brain" by Alba Naudí, Pilar Caro, Mariona Jové, José Gómez, Jordi Boada, Victoria Ayala, Manuel Portero-Otín, Gustavo Barja, and Reinald Pamplona. Rats undergoing methionine restriction had: higher mitochondrial complex 1 content and activity, higher complex 3 content, higher mitochondrial biogenesis factor PGC-1alpha, higher uncoupling protein 4, lower mtDNA oxdiation, lower membrane unsaturation in the brain.

"Muscular Transcriptome in Postmenopausal Women With or Without Hormone Replacement" by Eija Pöllänen, Paula HA Ronkainen, Harri Suominen, Timo Takala, Satu Koskinen, Jukka Puolakka, Sarianna Sipilä, and Vuokko Kovanen. What the title says. Randomised control study. HRT slows down the changes.

"Insulin-Like Growth Factor I Deficiency Prolongs Survival and Antagonizes Paraquat–Induced Cardiomyocyte Dysfunction: Role of Oxidative Stress" by Qun Li, Xiaoping Yang, Nair Sreejayan, and Jun Ren.  Mice without IGF-1 in their liver lived longer than C57 negative (standard branch?) mice when given paraquat (herbicide, poisonous). Their cardiomyocytes also behaved better in a whole bunch of measurements that I don't understand.

"Sufficiency, Justice, and the Pursuit of Health Extension" by Colin Farrelly. Philosophy.

"N-Glycomic Changes in Serum Proteins During Human Aging" by Valerie Vanhooren, Liesbeth Desmyter, Xue-En Liu, Maurizio Cardelli, Claudio Franceschi, Antonio Federico, Claude Libert, Wouter Laroy, Sylviane Dewaele, Roland Contreras, and Cuiying Chen. Changes in glycosylation of serum proteins with age in humans. Could be used as age or health marker.

"Hunger Does Not Diminish Over Time in Mice Under Protracted Caloric Restriction" by Catherine Hambly, Julian G. Mercer, and John R. Speakman. They measured how much mice eat when they are allowed after different periods of CR. They always eat more, they don't get accustomed to the CR. They keep eating until they get to normal weight.

"Theoretical Paper: Exploring Overlooked Natural Mitochondria-Rejuvenative Intervention: The Puzzle of Bowhead Whales and Naked Mole Rats" by Arkadi F. Prokopov. Something about intermittent hypoxic training/therapy being beneficial, and its benefits being based on a preserved mechanism that is related to intermittent oxygen restriction and intermittent caloric restriction. Not sure. Need to read the details.

"Xenogenic Transfer of Isolated Murine Mitochondria into Human ρ0 Cells Can Improve Respiratory Function" by Eyad Katrangi, Gerard D'Souza, Sarathi V. Boddapati, Mariola Kulawiec, Keshav K. Singh, Brian Bigger, and Volkmar Weissig. They show that mammal cells take up isolated mitochondria just by coincubation, that mice mitochondria transplanted into human cells without mtDNA restore respiration, and something about mitochondria taking up linear DNA easily, so combining that with the cells taking up the mitochondria makes them a good tool for studing mitochondrial genetics.

"Fusion and Regenerative Therapies: Is Immortality Really Recessive?" by Alexandra Stolzing, Jürgen Hescheler, and Sebastian Sethe. Overview of cell fusion experiments in aging and suggestions of future experiments for the purpose of rejuvenating cells. They claim that loss of regenerative capacity is because stem cells lose their ability to fuse effectively (I think that's what they are saying).

"Rhodiola: A Promising Anti-Aging Chinese Herb" by Mahtab Jafari, Jeffrey S. Felgner, Irvin I. Bussel, Tony Hutchili, Behnood Khodayari, Michael R. Rose, C. Vince-Cruz, and Laurence D. Mueller. They tested four chinese herbs on fruit fly, one of them, rhodiola, extended lifespan. Controlled for dietary restriction.

"Differential Effects of In Vitro Zinc Treatment on Gene Expression in Peripheral Blood Mononuclear Cells Derived from Young and Elderly Individuals" by D.J. Mazzatti, M. Malavolta, A.J. White, L. Costarelli, R. Giacconi, E. Muti, C. Cipriano, J.R. Powell, and E. Mocchegiani. Differential gene expression analysis of zinc intervention on mononuclear cells of young and old people.

"A Preliminary Analysis of Within-Subject Variation in Human Serum Oxidative Stress Parameters as a Function of Time" by Sandro Argüelles, Ana Gómez, Alberto Machado, and Antonio Ayala. Huge within-subject variability in oxidative stress markers and antioxidant capacity when taking three measurements per day on four days over a period of 51 days.

Issue 3, 2007

There are a lot of articles in this issue because they included the papers from the first Edmonton aging symposium.

"Human Reproductive Costs and the Predicted Response to Dietary Restriction" by Robert Arking. Attempts to predict the effects of CR on human longevity with a model based on energy allocation (I think).

"Autophagy in the Heart and Liver During Normal Aging and Calorie Restriction" by Stephanie E. Wohlgemuth, David Julian, Debora E. Akin, Joanna Fried, Kristin Toscano, Christiaan Leeuwenburgh, and William A. Dunn, Jr. Autophagy rates in the heart and liver are not affected by age in rats that eat what they want. It is increased by CR in old rats only in the heart, not in the liver.

"Apolipoprotein E Genotypic Frequencies Among Down Syndrome Patients Imply Early Unsuccessful Aging for ApoE4 Carriers" by Giusi I. Forte, Maria Piccione, Letizia Scola, Antonino Crivello, Cristina Galfano, Massimiliano M. Corsi, Martina Chiappelli, Giuseppina Candore, Mario Giuffrè, Roberto Verna, Federico Licastro, Giovanni Corsello, Calogero Caruso, and Domenico Lio. ApoE4 carriers go down as a proportion of the population at older ages (16% of people under 40, 13% of those in their 70s, and 4% of people over 90 in a study of 360 people). Down syndrome patients at 9% (106 DS average age 9). They use frequency difference between 5-year old DS people to those older to claim that DS is a good model of early aging.

"Dietary Intake of Elderly Living in Toronto Long-Term Care Facilities: Comparison to the Dietary Reference Intake" by Elaheh Aghdassi, Margaret McArthur, Barbara Liu, Alison McGeer, Andrew Simor, and Johane P. Allard. Old people in long term care facilities don't get a perfect diet, but not too bad either.

"Cytochrome c Oxidase Rather than Cytochrome c is a Major Determinant of Mitochondrial Respiratory Capacity in Skeletal Muscle of Aged Rats: Role of Carnitine and Lipoic Acid" by Jayavelu Tamilselvan, Kumarasamy Sivarajan, Muthuswamy Anusuyadevi, and Chinnakkannu Panneerselvam. I don't really understand much more than the title. They did experiments on naked mitochondria that had lost their cytochrome c and where bathing them in cytochrome c didn't recover their natural activity.

"A Model of Metabolic Changes in Respiration-Deficient Human Cells" by F. Mathias Bollmann. A model of how cells with damaged mitochondria survive long term through the combination of glycolysis and a 'partly reversed TCA cycle'. Needs to export succinate.

Following papers from the Edmonton aging symposium

"Mitochondria in Aging and Alzheimer's Disease" by P.J. Crouch, K. Cimdins, J.A. Duce, A.I. Bush, and I.A. Trounce. They postulate that mtDNA mutations are an important factor in amyloid beta production. They say amyloid beta accumulates in mitochondria in Alzheimered brains.

"Engineering Away Lysosomal Junk: Medical Bioremediation" by Bruce E. Rittmann and John Schloendorn. Strains of Nocardia (a bacteria) can degrade 7-ketocholesterol, although it's tricky to tell from the grammar of the sentence to what, or if it can be degraded without modifications. They have some analysis of the intermediate molecules in the degradation pathway.

"Therapeutic Ultrasound Applications in Craniofacial Growth, Healing and Tissue Engineering" by Tarek El-Bialy. Ultrasound being trialled/used to trigger/speed up bone formation/healing and dental formation. This paper claims to explain the molecular basis for this.

"Time, Damage, and Aging: What Really Matters?" by Huber R. Warner. Not sure.

"Nutrition as a Determinant of Successful Aging: Description of the Quebec Longitudinal Study NuAge and Results from Cross-Sectional Pilot Studies" by Pierrette Gaudreau, José A Morais, Bryna Shatenstein, Katherine Gray-Donald, Abdel Khalil, Isabelle Dionne, Guylaine Ferland, Tamàs Fülöp, Danielle Jacques, Marie-Jeanne Kergoat, Daniel Tessier, Richard Wagner, and Hélène Payette. Longitudinal study of 1800 >68 year olds tracking lots of variables. Hasn't finished yet, this is just the description.

"The Cancer–Aging Interface and the Significance of Telomere Dynamics in Cancer Therapy" by Gesche Tallen, Mohamed A. Soliman, and Karl Riabowol. Chemotherapy triggers faster cell regeneration in healthy tissue to compensate for lost cells. This leads to shorter telomeres, which could have some impact down the line.

"Loss of Muscle Strength During Aging Studied at the Gene Level" by Geoffrey Goldspink. Mechano-growth factor, an alternative splicing of IGF-1, increases muscle contractile strength by activating muscle satellite stem cells that do local muscle repair.

Issue 2, 2007

By the abstracts.

"Allotopic mRNA Localization to the Mitochondrial Surface Rescues Respiratory Chain Defects in Fibroblasts Harboring Mitochondrial DNA Mutations Affecting Complex I or V Subunits" by Crystel Bonnet, Valérie Kaltimbacher, Sami Ellouze, Sébastien Augustin, Paule Bénit, Valérie Forster, Pierre Rustin, José-Alain Sahel, and Marisol Corral-Debrinski. Another mitoSENS contribution like the one in issue 4 of 2006 by Bokori-Brown, this one claiming success in both getting the proteins to migrate to the mitochondria and them functioning as expected and rescuing cells with mtDNA mutations in their ATP6 and ND4 genes. They seem to be stressing the result for ATP6 so maybe the result for ND4 isn't as clear-cut. How many left out of the 13 then?

"Microsatellite Instability and Compromized Mismatch Repair Gene Expression During In Vitro Passaging of Monoclonal Human T Lymphocytes" by Simona Neri, Graham Pawelec, Andrea Facchini, and Erminia Mariani. I don't know enough about T-cells, mismatch repair or microsatellite instability to even understand what this study was about.

"The Olive Constituent Oleuropein Exhibits Proteasome Stimulatory Properties In Vitro and Confers Life Span Extension of Human Embryonic Fibroblasts" by Magda Katsiki, Niki Chondrogianni, Ioanna Chinou, A. Jennifer Rivett, and Efstathios S. Gonos. 15% is the claimed lifespan extension on fibroblasts.

"Oxidative Stress of Neural, Hematopoietic, and Stem Cells: Protection by Natural Compounds" by R. Douglas Shytle, Jared Ehrhart, Jun Tan, Jennifer Vila, Michael Cole, Cyndy D. Sanberg, Paul R. Sanberg, and Paula C. Bickford. Lower oxidative stress-induced apoptosis in some human cells in vitro when given some code-named natural compound.

"Examination of Cognitive Function During Six Months of Calorie Restriction: Results of a Randomized Controlled Trial" by Corby K. Martin, Stephen D. Anton, Hongmei Han, Emily York-Crowe, Leanne M. Redman, Eric Ravussin, Donald A. Williamson, and for the Pennington CALERIE Team. Randomised controlled CR study on humans. These are rare. Checked to see if there was any cognitive impairment but found none. 12 people per group, so it would have had to have been a big effect to have been found, but still something.

"Oxidative DNA Damage Repair and parp 1 and parp 2 Expression in Epstein-Barr Virus-Immortalized B Lymphocyte Cells from Young Subjects, Old Subjects, and Centenarians" by Marta Chevanne, Corinne Calia, Michele Zampieri, Barbara Cecchinelli, Riccardo Caldini, Daniela Monti, Laura Bucci, Claudio Franceschi, and Paola Caiafa. They find some properties of B-cells in centenarians that resemble the properties found in young people and differ from old non-centenarians (sub-centenarians?). I never buy these ones.

"Mathematical Models for the Proliferation of Neural Stem/Progenitor Cells in Clonogenic Culture" by Bao Feng Ma, Xiao Mei Liu, Ai Xia Zhang, Peng Wang, Xiu Ming Zhang, Shu Nong Li, Bruce T. Lahn, and Andy Peng Xiang. What it says on the title. Without access to the paper, can't tell anything about the model.

"Mitochondrial Oxygen Consumption and Reactive Oxygen Species Production are Independently Modulated: Implications for Aging Studies" by Gustavo Barja. Claims that sometimes higher oxygen consumption means lower ROS production. eg aerobic exercise, chronic exercise, hyperthyroidism and dietary restriction. Also, that it is lower in long-lived birds than in mammals of the same size.

"Long-Term Low-Calorie Low-Protein Vegan Diet and Endurance Exercise are Associated with Low Cardiometabolic Risk" by Luigi Fontana, Timothy E. Meyer, Samuel Klein, and John O. Holloszy. Raw vegans and runners were healthier than normal people, all groups around 53 (11) years. Lower weight, plasma lipids, lipoproteins, glucose, C-reactive protein, blood pressure and carotid artery intima-mdedia thickness. Also, raw vegans had lower BP than runners.

In the first page of the now-seemingly-regular column surveying theses, there is a thesis looking at parental imprinting comparison in cattle between cloned and natural animals, and finding big variability among cloned animals, and differences from natural animals, especially mentioning IGF2.

Issue 1, 2007

Back to not having access to the full text on this issue.

"Old Rhesus Macaques Treated with Interleukin-7 Show Increased TREC Levels And Respond Well to Influenza Vaccination" by Richard Aspinall, Jeffrey Pido-Lopez, Nesrina Imami, Sian M. Henson, Pa Tamba Ngom, Michel Morre, Henk Niphuis, Ed Remarque, Brigitte Rosenwirth, and Jonathan L. Heeney. What it says on the title. TREC are T-cell receptor excision circles, wikipedia tells me, which are small circles of DNA created during the time the T-cell spends in the thymus while creating the huge variety of receptors, and are a marker for mature T-cells. Old here is 18.5 to 23.9 years.

"A Novel Possible Approach to The Creation of Genetically Personalized Human Embryonic Stem-Like Cell Lines" by Wenqing Fu. Proposal for a technique to create tailored hESCs by repeatedly merging a generic line of hESCs with the target human's line, growing it to a blastocyst, pulling hESCs from that and repeating the process. I'd think the invention of iPSCs obviated the need for doing this.

"Correction of Proliferation And Drug Sensitivity Defects in The Progeroid Werner's Syndrome by Holliday Junction Resolution" by Ana M. Rodriguez-Lopez, Matthew C. Whitby, Christine M. Borer, Marcus A. Bachler, and Lynne S. Cox. They insert a bacterial enzyme that removes Holliday junctions from Werner's syndrome cells. The cells do better afterwards.

"Impaired Mononuclear Cell Immune Function in Extreme Obesity Is Corrected by Weight Loss" by Luigi Fontana, J. Christopher Eagon, Marco Colonna, and Samuel Klein. Very small study on six extremely fat people. They had very low production of two immune-system stimulating factors. Losing 30% of their weight fixed that. The whys for the low immune system stimulation and recovery seem not to be known.

"Reactive Oxygen Species, Isotope Effect, Essential Nutrients, and Enhanced Longevity" by Mikhail S. Shchepinov. Change the carbons and hydrogens to heavier isotopes than normal to slow down ROS reaction and therefore live longer.

"Evidence That Aging And Amyloid Promote Microglial Cell Senescence" by Barry E. Flanary, Nicole W. Sammons, Cuong Nguyen, Douglas Walker, and Wolfgang J. Streit. Shorter telomeres in human microglia when demented. Shorter telomeres and lower telomerase activation in rat microglia with aging. Microglia dystrophy in demented and amyloidal humans compared to non-demented non-amyloidal.

"Cumulative Index of Elderly Disorders And Its Dynamic Contribution to Mortality And Longevity" by Anatoli I. Yashin, Konstantin G. Arbeev, Alexander Kulminski, Igor Akushevich, Lucy Akushevich, and Svetlana V. Ukraintseva. An absolute and relative risk function of age that I think I need to see to understand.

"Cellular Therapy Using Microglial Cells" by John Schloendorn, Sebastian Sethe, and Alexandra Stolzing. Sounds like a theoretical paper on what we could do to keep microglia functioning properly and also improve their function by inserting proteases from other species into precursors that can then cross the blood-brain barrier. Might have to look for it.

There's a summary of PhD dissertations there that would be interesting to see too.

Issue 3, 2006

By the abstracts:

"Targeting Telomerase". Review of techniques and issues regarding hammering telomerase as an anti-cancer treatment, and whether that would select for ALT-cancers (ALT constitute 10-15% of cancers atm). Of note, the existence of a TERT vaccine.

"Telomere and TRF2/MTBP Localization in Respect to Satellite DNA During the Cell Cycle of Mouse Cell Line L929" About what happens to telomeres as the cells goes through its cycle in mice. Mostly goes over my head.

"Werner Syndrome as an Example of Inflamm-aging: Possible Therapeutic Opportunities for a Progeroid Syndrome?" Title is a good summary of the abstract.

"Stimulation of Macroautophagy Can Rescue Older Cells from 8-OHdG mtDNA Accumulation: A Safe and Easy Way to Meet Goals in the SENS Agenda" They stimulate macroautophagy by injecting agents that stop the breakdown of triglycerides in rat liver cells. This gets rid of 8-OHdG accumulation in the mtDNA in six hours.

Also, a report on SENS 2 by Aubrey de Grey that I'd like to read.

Overall, I don't mind as much not having access to the articles in this issue.

Issue 2, 2006

This issue is the second part of the papers presented in SENS 2005. By the abstracts:

Section 5: Mitochondria and Oxidative Damage

"Extracellular Redox State: Refining the Definition of Oxidative Stress in Aging" suggests that blood glutathione/glutathione disulfide ratio does not equilibrate with blood cysteine/cystine ratio, that the latter is not just a diagnostic but that it affects cell proliferation and oxidant-induced apoptosis, and that both ratios are good controlling indicators of oxidative stress. Or something like that, I haven't done this for a while and seem to have lost the knack. Lots of citations for this one.

"Factors That Might Affect the Allotopic Replacement of a Damaged Mitochondrial DNA-Encoded Protein". Review of successful allotopic expression of mitochondrial genes ported to the nuclear DNA and possible issues with getting those proteins into the inner membrane of the mitochondria. Sounds interesting.

"Can a Single Subunit Yeast NADH Dehydrogenase (Ndi1) Remedy Diseases Caused by Respiratory Complex I Defects?" They introduced NDi1, which transfers electrons from NADH to ubiquinone in yeast, into mammalian cells, some missing Complex 1. NDi1 inserted itself into the inner membrane of mitochondria and rescued the cells that were lacking Complex 1. They got it working on mice muscles and brains. Interesting.

"Protective Efficacy of α-Lipoic Acid on Acetylcholinesterase Activity in Aged Rat Brain Regions". Pumped alpha-lipoic acid into old rats, saw acetylcholinesterase levels restored in some parts of their brain.

"Cytochemical Estimation of Cytochrome Oxidase Activity as a Morphofunctional Mitochondrial Check-Up". They propose that measuring the ratio of cytochemical precipitate to mitochondrial area would give a good indication of mitochondrial function since the ratio decreased by 25% with aging.

"From Disease-Oriented to Aging/Longevity-Oriented Studies". Not sure what this is. Abstract sounds like the general aging IS a disease drive, with a focus on epigenetics, but hard to tell. Quite a few citations.

"Tissue-Specific Effect of Age and Caloric Restriction Diet on Mitochondrial DNA Content". CR reversed the drop in mtDNA in old rat livers and leg muscles, and increased the mtDNA of the brain, even though there is no drop there in ad-libitum rats.

"Testing Mitochondrial Metabolic Competence by Cytochrome Oxidase Preferential Cytochemistry Versus Immunoreactivity of Subunits I and IV". COX activity dropped with age in rats but not levels of two of its subunits.

"Caloric Restriction Protects Mitochondrial Function with Aging in Skeletal and Cardiac Muscles" 25 to 46% drop in oxidative capacity markers for ad-libitum-fed 'animals' (who knows what animals). None for CR. A lot of citations.

"Mitochondrial Genome Anatomy and Species-Specific Lifespan"  Maximum lifespan is correlated with amount of cytosine in the DNA of mammal species, especially for primates. Vaguely interesting.

"Relationship Between Aging and Susceptibility of Erythrocytes to Oxidative Damage: In View of Nutraceutical Interventions". Placebo-controlled study feeding fermented papaya preparation to old people. Rescued abnormal higher concentration of nitric oxide synthase and malondialdehyde (a marker for oxidative stress) in red blood cells of old people compared to young people.

"Aging-Related Cell Surface ECTO-NOX Protein, arNOX, a Preventive Target to Reduce Atherogenic Risk in the Elderly". Cell-surface electron-transport protein associated with aging that can produce superoxide and thus oxidise circulating lipoproteins.


Section 6: Molecular Crosslinking and Aggregation

"Emerging Strategies for the Treatment of Hereditary Metabolic Storage Disorders" looks at solutions other than enzyme replacement for Gaucher and Fabry disease, which are diseases caused by mutations to enzymes that break down the stuff left over when senescent cells die.

"Advanced Atherosclerotic Foam Cell Formation Has Features of an Acquired Lysosomal Storage Disorder". Reviews the evidence for the foam cells in atherosclerosis to be due to an acquired lysosomal storage disorder. That is, the lysosomes are failing to break down what is sent to them so the material acumulates in the cell. Quite a few citations for this one.

"Indirect Antioxidant Protection Against Photooxidative Processes Initiated in Retinal Pigment Epithelial Cells by a Lipofuscin Pigment". Claims lipofuscin A2E triggers oxidation damage in retinal epithelial cells and is protected from this by glutathione and sulforaphane.

"Prevention and Repair of Protein Damage by the Maillard Reaction In Vivo". Equivalence between Maillard recation and advanced glycation end products (AGEs). 20 AGEs in human skin. No evidence of AGE breakers of breaking crosslinks in vivo. Maybe interesting, at least to learn about AGEs.

"Extracellular Glycation Crosslinks: Prospects for Removal". Two proposed methods of getting rid of glucosepane and K2P crosslinks. One is upping extracellular matrix turnover. A second one is high-throughput screening for molecules that can break those two down.


Section 7: Miscellaneous

"Cryopreservation of Complex Systems: The Missing Link in the Regenerative Medicine Supply Chain". On the potential use of vitrification to store organs, created through regenerative medicine, for transplanting when necessary. Claims routine recovery of vitrified rabbit kidneys cooled to -45 degrees celsius functioning properly after rewarming and being transplanted back into rabbits. Found the article. Might write one for it.

"Cryptobiosis, Aging, and Cancer: Yin-Yang Balancing of Signaling Networks". Aging as unbalanced complex signaling pathways.

"The Neurosecretory System Is Hypertrophied in Senescence-Accelerated Mice". Analysis of the neurosecretory system of senescence-accelerated mice.

"Natural Background Radioactive Carbon and the Natural Death Rate of People". Correlation between levels of carbon-14 in the atmosphere and death rates over the last 150 years. Notable mainly because the author's organisation is given as 'independent researcher'. Didn't think that was possible in this century.

"Radiocarbon Mechanism of Aging". More on carbon-14 and death rates by independent researchers, offering a mechanism of aging by carbon-14.

"Variations of Humans' Natural Death Rate and the Radiocarbon Aging Mechanism". More carbon-14 and mortality.

"Statistical Issues of Regression Analysis on Development of an Age-Predictive Equation". Equations to predict age from physical fitness measurements training on 31 Japanese males.

"Soft Strategies for Postponing Aging and Prolonging Human Life". Postponing aging by looking at things that cause discomfort and stopping things from becoming major.

"Psychosocial Aspects and Zinc Status: Is There a Relationship with Successful Aging?". Low albumin, as indicator for zinc, correlated with higher levels of depression in old Italians.

"Liver Exposure to Xenobiotics: The Aging Factor and Potentials for Functional Foods". Study on liver cells from young and old rats cultured with and without alpha-linolenic acid and given YHK (a herbal supplement I'd never heard of) or sylibin. They then gave them copper and iron. YHK did better at some things.

"The Aging Gut Motility Decay: May Symbiotics Be Acting as "Implantable" Biologic Pace-Makers?" Symbiotic (I don't know what that is) SCM-III (also no idea) does something to old rats' colons and jejunum.

"How Evolutionary Thinking Affects People's Ideas About Aging Interventions". From a person that belong to the group that think that aging is an evolutionarily programmed response. Mentions apoptosis and senescence via telomere shortening as behaviours that seem to shorten lifespan. Also, NSAIDs slowing arthritis, cancer and atherosclerosis as evidence for inflammation as programmed autoimmune response.

"Zinc Homeostasis in Aging: Two Elusive Faces of the Same 'Metal'". Aging creates zinc dyshomeostasis, not zinc deficiency.

"Aging and Oral Health Related to Quality of Life in Geriatric Patients". Survey of 53 70-year old Bulgarians regarding reasons they go to the dentist. 32% for acute pain and the rest for caries.

"Is Thrombolytic Therapy Effective in Elderly Patients?". Clinical (single-arm?) study doing thrombolytic therapy on 103 heart attacked people over 75. They say it had a positive effect.

"Negligible Senescence: How Will We Know It When We See It?". Suggests the use of global index of aging rate as units of functional change per time.

Issue 1, 2006

This issue and the next are all about the SENS 2005 meeting. I'm still going by the abstracts though, since that's the best I've got.

Section 1: Stem Cells and Regeneration

"Conjecture: Can Continuous Regeneration Lead to Immortality? Studies in the MRL Mouse". Separate summary since I found the article and it sounded interesting

"Sustained Stromal Stem Cell Self-Renewal and Osteoblastic Differentiation During Aging". Characterisation of a line of stem cells isolated in bone marrow that can differentiate into all (?) other types. Frequency decreases from 0.01% of bone marrow cells when 3 years old to 0.0018% at 45 but doesn't go down after that. Interesting but probably too basic-sciency to incorporate.

"To Make a New Intestinal Mucosa". Grabbed some rats, chopped a quarter of their small intestine, making them leak bile in their shit, grabbed intestinal stem cells from newborn rats, and combined them with a separate bit of cleaned up section of intestine (from different rats I assume), and inserted the reformed bit at the end of their small intestines. Worked (as in no more bile leakage). They also did some other experiment with plastic scaffolds and being able to look at the implanted cells in vivo. It all sounds interesting.

"Transfection of CCE Mouse Embryonic Stem Cells with EGFP and BDNF Genes by the Electroporation Method".  They show they can insert genes into stem cells by electroporation of plasmids and have them expressed.

"Glucose-Induced Replicative Senescence in Mesenchymal Stem Cells". Calorie restriction experiment in-vitro in which the mesenchymal stem cells which get less sugar die less and have higher replicative potential.


Section 2: Cancer, Cell Senescence, and Telomeres

"Gene Therapy That Safely Targets and Kills Tumor Cells Throughout the Body". Separate summary.

"Catechin-Vanilloid Synergies with Potential Clinical Applications in Cancer". Combination of two molecules inhibit expression of tNOX which is a molecule supposedly expressed only in cancers, and supposedly necessary for cancer growth.

"Multilocus Genotypes Spanning Estrogen Metabolism Associated with Breast Cancer and Fibroadenoma". Analysis of correlations between multiple SNPs associated with estrogen and breast cancer and fibroadenoma. They think they found something that increases risk 25 times. Study of 2500 people.

"Analysis of Telomere Length and Telomerase Activity in Tree Species of Various Lifespans, and with Age in the Bristlecone Pine Pinus longaeva". They compare telomere length and telomerase activity of bristlecone pines, which live for thousands of years to shorter lived trees. They think there's something there.

"Mitochondrial Dysfunction and Cell Senescence: Cause or Consequence?". Look at evidence of mitochondria's role in senescence. They say it's complicated. Sounds interesting but can't find it.

"Chromatin Modification and Senescence: Linkage by Tumor Suppressors?". Investigation of chromatin-modification path to senescence and potential genes involved. Maybe interesting.


Section 3: Neurodegeneration

"Amyloid-Beta Immunotherapy for the Prevention and Treatment of Alzheimer Disease: Lessons from Mice, Monkeys, and Humans". Seems to be a review of the experiments that have been performed in attacking amyloid beta through immunotherapy.

"Synaptic Pathology in the Brain Cortex of Old Monkeys as an Early Alteration in Senile Plaque Formation".  Measurements of synaptic density in old monkeys compared to adult monkeys. I don't understand the measurements, except for the one where it says that the number of synapses per neuron go down by about 20% in the temporal cortex, but not in the frontal cortex.

"Membership in Genetic Groups Predicts Alzheimer Disease". Allele group analysis correlations with Alzheimer's. They think they found something with 800 times risk. 300 people in study.

"Level and Distribution of Microtubule- Associated Protein-2 (MAP2) as an Index of Dendritic Structural Dynamics". More comparison of measurements between the brains of old rats and adult rats that I don't understand.

"Association Between the HLA-A2 Allele and Alzheimer Disease". They find that 46% of their study group with AD have the HLA-A2 allele vs 38% of controls.

"Structural Synaptic Remodeling in the Perirhinal Cortex of Adult and Old Rats Following Object-Recognition Visual Training". And yet more measurements comparing synaptic densities in old and adult rats. This time, it is after the rats learn something.

"The nACHR4 594C/T Polymorphism in Alzheimer Disease". Analysis of correlations between variants of the neuronal nicotinic acetylcholine receptor and AD. Study of 140.


Section 4: Immunosenescence

"Immunorejuvenation in the Elderly". About possible ways to restore the immune system from its cytomegalovirus obsession by killing those T-cells, regrowing the thymus and hammering CMV with drugs. Sounds interesting but I can't find it.

"Antibody Quality in Old Age". So supposedly, the specificity of antibodies produced against antigens decreases with age. They think this is due to laxer selection in the germinal centers of mucosal tissue.

"Immunomodulatory Vaccines Against Autoimmune Diseases". Description of therapeutic vaccines against multiple sclerosis and myasthenia gravis, an autoimmune neuromuscular disease.

"A Novel Approach to Thymic Rejuvenation in the Aged". They implant cells that produce interleukin-7 into old thymus and it seems to help. Another one that sounds interesting but that I cannot find.

"Biology of Longevity: Role of the Innate Immune System". Seems to be a review of the links between the immune system and longevity. Could be interesting. Hard to tell from the abstract. Can't find it anyway.

"Memory B Cell Subpopulations in the Aged". Lower blood levels of IgD in the blood of old people, higher level of CD19+CD27+ memory cells. Negative correlation between the two. Too many memory cells, not enough naive.

"Analysis of Candidate Genes in Celiac Disease: A Tool to Identify Life-Threatening Associated Genes?" They find no difference in the frequencies of the transforming growth factor beta 2 alleles between celiac disease patients, healthy patients and healthy people over 95 year old.

"Analysis of HLA-DQA, HLA-DQB Frequencies in a Group of Sardinian Centenarians". No significant differences between observed and expected frequencies of HLA-DQA1 and HLA-DQB1 in centenarians.

Issue 4, 2005

By the abstracts:

"Two Hands Make Light Work of Gene Modification". About a then new DNA-modification technique where they combined zinc-fingers and nucleases to chop the DNA wherever they wanted. The idea is to put a suitable replacement patch into the cell, and letting the cell's repair system patch the substitute in. A very similar idea has been making the rounds lately and has been advertised as an easier and cheaper version of the one used in this paper.

"Mitochondrial DNA Mutations, Apoptosis, and the Misfolded Protein Response" seems to be a theoretical paper postulating a mechanism explaining the results of experiments in mice with mutant mitochondrial DNA polymerase. They claim that the main way that mitochondrial mutations drive aging is that mutated proteins occasionally trigger apoptosis by interacting with mitochondrial membrane proteins. This then triggers compensatory effects of the tissue to this loss of cells. In the abstract they mention that heart tissue upregulates anti-apoptotic signals and also drives the rest of the surviving heart cells hard to compensate for pumping loss. In this model, ROS triggers the mtDNA mutations but is not a major part of the downstream mechanism (sort of the reverse of http://readingrejuvenationresearch.blogspot.com.au/2013/03/mitochondrial-microheteroplasmy-and.html, although very obviously related).  I found a summary that looks to be an extract from the paper at http://crabsallover.blogspot.com.au/2006/11/mitochondrial-dna-mutations-apoptosis.html. I'll read the rest if I find it.

"Cellular Responses to Protein Accumulation Involve Autophagy and Lysosomal Enzyme Activation". Study of what happens when high level of protein gunk builds up on neurons in vitro. Lysosomes and macroautophagy are activated, but not enough to compensate.

"A Yang-Invigorating Chinese Herbal Formula Enhances Mitochondrial Functional Ability and Antioxidant Capacity in Various Tissues of Male and Female Rats". Chinese herbal formula upregulates SODs in rats.

"NANOG Changes in Mouse Kidneys with Age". Tracking of expression of NANOG, gene needed to keep pluripotency and one of the genes introduced to create iPSCs later, in mice's kidneys as they age. Expression goes down.

Also, there was a report on the 11th Congress of the International Association of Biomedical Gerontology which I'd like to read.

Issue 3, 2005

By the abstracts:

"A New Tool in the Battle Against Alzheimer's Disease and Aging: Ex Vivo Gene Therapy". Analysis of a phase 1 trial of using ex-vivo gene therapy to somehow pump nerve growth factor to the basal forebrain of people with Alzheimer's, results of which are seen as mildly beneficial. I can't tell how they got the cells to go into the brain. More interesting from the gene therapy side than from the Alzheimer's side.

"H₂S-Induced Ectothermy: Relevance to Aging". Look at the use of hydrogen sulfide as a suspended-animation conduit to extend lifespan of currently living till engineered negligible senescence arrives.

"Oxidative Stress and Aging: Catalase Is a Longevity Determinant Enzyme". Analysis of result where catalase was upregulated in cardiac mitochondria and skeletal muscle in mice, which led to lifespan increase of 20%. Famous result. I should have a look at it, and maybe find the original research by Schriner too.

"Ontogenetic Decline of Regenerative Ability and the Stimulation of Human Regeneration". Description of the problem of in-situ tissue regeneration, and on getting useful information from salamanders on how they do it. Two steps to tissue regeneration in salamanders, the first, which we are not capable of, is formation of a regeneration blastema, while he claims we are capable of the second step. Fibroblasts drive the first step by dedifferentiating into the blastema. Interesting.

"The Concept of Telomeric Non-Reciprocal Recombination (TENOR) Applied to Human Fibroblasts Grown in Serial Cultures: Concordance with Genealogical Data". Review of what is currently known about telomere-shortening triggering senescence in fibroblasts, and how those telomeres are sometimes elongated by telomeric non-reciprocal recombination. I should have a look.

"Mitochondrial Microheteroplasmy and a Theory of Aging and Age-Related Disease". The majority of mitochondria contain mutations, but each specific mutation is rare (1-2%). Theorising from that. Should read.

Issue 2, 2005

By the abstracts:

"Replicative Aging in E. coli". About pausible aging in E Coli. Cells from parts of the cell that are older grow slower and die more. The rate seemed to be linear, not exponential, although it would be hard to tell with low numbers.

"The Role of Microglial Cellular Senescence in the Aging and Alzheimer Diseased Brain". What the title says. Microglias get fucked up in old people. This could be due to or cause senescence. This could be bad for the brain.

"Testing Whether Male Age or High Nutrition Causes the Cessation of Reproductive Aging in Female Drosophila melanogaster Populations". Reproduction in fruit flies drops with age but then stops dropping at late age (fecundity plateau). They test whether giving old female fruit flies young male studs helps, and whether amount of food helps. Both interventions changed things, but didn't get rid of the fecundity plateau.

"Clinical Anti-Aging Hormetic Strategies". Seems to be an analysis or reinterpretation of several life extension  strategies (calorie restriction, exercise, social interaction) as forms of hormetic therapy. Hormetic = low level and repeated stress that causes benefits by triggering the body's defenses.

"Kidney Aging: From Phenotype to Genetics". What the title says. A review.

Nothing that I'm very pissed off on missing out on.