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.