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.