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 4, 2006

For some reason, this issue is free so I can read any articles I feel interested in, but since I don't really have any time to read papers, I will stick mostly to the abstracts.

There is a series of comment articles that are followups to the Special Interest Group on Societal Implications of Anti-Aging Research at the the 2005 Gerontology Society of America's conference discussing the usual SENS vs nonSENS.

"Site-Specific Integration into the Human Genome: Ready for Clinical Application?". A commentary piece on the possibilities of practical use of adeno-associated virus (AAV) for clinical gene insertion. AAV can insert its genome into a specific part of chromosome 19 (AAVS1), but it can only carry a very small payload. To enlarge the payload it's usually used without the site-specific integration gene (Rep) which ruins the reason for using AAV in the first place. What was new work at the time was a development of a hybrid between the herpes simplex virus and AAD to keep the site-specific integration while enlarging the payload and not overdoing the Rep expression which otherwise causes problems. Article says it isn't good enough for the clinic yet because the site-specificity isn't good enough (70%) and because of low efficiency of gene transfer which they claim to be 20% for stable cell lines (my problem here is that I don't know what the efficiency means. That 20% of the cells get the gene inserted into them sounds like the most likely meaning).

"Mitochondrial Transfer Between Eukaryotic Animal Cells and Its Physiologic Role". Another commentary piece on a paper that appeared in PNAS reporting the rescue of cells grown without mtDNA when grown among normal human skin fibroblasts and mesenchymal stem cells in vitro. By rescue, they mean that after a while, the sans-mtDNA cells appear to acquire functional mitochondrial and they multiply as normal. The commentary is on the mechanism of mitochondrial transfer and on whether the usual function of mitotransfer is that good mitochondria flow from good cells to bad cells or the reverse, the first one as an analogy to entropy, the second seeing mitochondria as selfish agents. The author prefers the first option.

"Expression of Algal Nuclear ATP Synthase Subunit 6 in Human Cells Results in Protein Targeting to Mitochondria but No Assembly into ATP Synthase" by M Bokori-Brown and IJ Holt. Very interesting and thorough attempt at introducing a version of the human subunit a (A6) of ATP synthase gene into a human cell's nuclear DNA. They tried many versions and the one that targeted to the mitochondria best was a version from an algae (Chlamydomonas reinhardtii) that is naturally in the nDNA, with various hybrids working less well. The problem is that the better the protein was targetted, the worse the cell did. Some more imagery shows that the protein doesn't colocalise with the ATP synthase on the mitochondria, so it's just gunking up the mitochondria, not doing anything useful.

"Erythrocyte Plasma Membrane Redox System in Human Aging" by SI Rizvi, R Jha and PK Maurya. Correlation of 0.78 between the level of export of electrons by red blood cells through the plasma membrane redox system, and age in 80 people. Similar inverse correlation between plasma antioxidant capacity and age.

"Selegiline Induces Neuronal Phenotype and Neurotrophins Expression in Embryonic Stem Cells" by F Esmaeili, T Tiraihi, M Movahedin and SJ Mowla. What the title says.

"VEGF Gene and Phenotype Relation with Alzheimer's Disease and Mild Cognitive Impairment" by M Chiappelli, B Borroni, S Archetti, E Calabrese, MM Corsi, M Franceschi, A Padovani and F Licastro. Link between a variant in the vascular enthelial growth factor (VEGF) gene promoter and Alzheimer's and mild cognitive impairment in a study of about 1000 people total. AA variant were 1.6 times more common than expected among AD. Also deteriorated fast 6 times more often if they had an ApoE4 allele. AA variant had more VEGF in circulation.