http://science-of-aging.healthaliciousness.com/ Papers on the Science of Aging. en-us webmaster@healthaliciousness.com 5 http://science-of-aging.healthaliciousness.com/timelines/weismann-germ-line.php In his 1893 book The Germ Plasm, August Weismann introduced the concept of a germ line and somatic line in the development of organisms. The concept was drawn, in part, by contrasting Darwin's theory of Pangenesis, the central dogma of the time. Darwin's theory suggested that the body's cells emit hundreds of gemmules which aggregate in the reproductive organs prior to fertilization. This implies that the somatic line(cells of the body) contribute to the germ line(cells of reproduction). Weismann's brilliance was to suggest the opposite, that the somatic line originated from the germ line, and the germ line itself remained forever separate and apart from the somatic cells of the body. Let us assume that the germ contains millions of the primary constituents ('Anlagen') of all the most minute portions of the body; moreover, that these constituents are always present at the right place and in the right combination during the process of development; and further, that they are capable of giving rise in their turn to the parts or organs to which they severally correspond. Such a theory explains everything, or nothing -- the premises along can be attacked. No new problems can arise from it till it has been placed upon a sound basis; the premises must be shown to be correct, and it must be proved that the germ is actually composed of primary constituents, which by some means or other become combined into groups and are capable of giving rise to the various parts and organs in question. Then, and then only, would the theory serve as an incentive to further investigations into the phenomena of heredity of all kinds, and experiments might be made which would support or contradict it...What first struck me when I began seriously to consider the problem of heredity, some ten years ago, was the necessity for assuming the existence of a special organized and living hereditary substance, which in all multicellular organisms, unlike the substance composing the perishable body of the individual, is transmitted from generation to generation. This is the theory of the continuity of the germ plasm. My conclusions led me to doubt the usually accepted view of the transmission of variations acquired by the body (soma); and further research, combined with experiments, tended more and more to strengthen my conviction that in point of fact no such transmission occurs. Meanwhile, the investigations of several distinguished biologists - in which I myself have had some share -- on the process and conjugations, brought about a complete revolution in our previous ideas as to the meaning of this process, and further led me to see that the germ-plasm is composed of vital units, each of equal value, but differing in character, containing all the primary constituents of an individual. The key concepts in Weismann's work was not only to place the germ cells in a commanding role of development of the somatic body, but also to set the germ cells apart from the body. The resultant conclusion from this separation is that while somatic cells are susceptible to aging, the germ line cells are passed from generation to generations apparently invulnerable to deterioration. http://science-of-aging.healthaliciousness.com/timelines/weismann-germ-line.php Fri, 17 Jul 2009 12:22:34 MST http://science-of-aging.healthaliciousness.com/timelines/Sharpless-DePinho-stem-cell-aging.php eased p53 expression or telomere shortening in aging tissue, which suggests causes for aging that are independent of tumor suppression.4,5,6 However, another explanation is that the tumor suppression/aging trade off only occurs in stem cells, a relatively small portion of cells in most tissues, and is thus, not detectable. The paper concludes suggesting that P16INK4a, p53, and telomere shortening can create useful biomarkers so medical professionals can make recommendations on lifestyle choices which can slow aging and reduce risk of cancer. As of 2009 P16INK4a has been found as a reliable biomarker of aging for a wide variety of human tissues.7 http://science-of-aging.healthaliciousness.com/timelines/Sharpless-DePinho-stem-cell-aging.php Thu, 09 Jul 2009 21:38:17 MST http://science-of-aging.healthaliciousness.com/timelines/gershon-inactive-enzyme-molecules.php In the late 1960s David and Harriet Gershon noticed from previous research that nematodes experienced a decline in enzymatic expression with age. The question then was: Is this decline due to a reduction in the number of enzymes per cell, or in the accumulation of inactive molecules? To answer this question they chose the nematode Turbatrix aceti since it has a short 25-30 day lifespan, and lacks regenerative capacity outside of the reproductive system. They then raised several populations of T. aceti and harvested them at different ages to assay for expression of the isocitrate lyase enzyme. The assay consisted of generating antibodies for the enzyme samples from the blood of rabbits, and measuring expression of the antibodies. The results showed lower enzyme expression per unit of antigen for samples taken from older nematodes. This results suggest that while older nematodes have active enzymes, they also carry large amounts of damaged enzymes that are no longer functional. The Gershons conclude stating that it would be interesting to understand the exact mechanism which causes the accumulation of inactive enzymes in the nematodes and if this phenomenon occurs in other organisms. They caution that investigations of enzyme activity due to age must go beyond measuring specific activities, as it appears old cells synthesize a larger number of molecules than younger cells. They also theorize that this extra energy expenditure creates a burden which leads to senescence. http://science-of-aging.healthaliciousness.com/timelines/gershon-inactive-enzyme-molecules.php Wed, 01 Jul 2009 10:38:27 MST http://science-of-aging.healthaliciousness.com/timelines/glucocorticoid-cascade-hypothesis.php In 1986 Robert Sapolsky, Lewis C. Krey, and Bruce McEwen published an 18 page review article in the Journal of Endocrinology outlining the Glucocorticoid Cascade Hypothesis of Aging. The hypothesis itself is not presented strictly as a cause of aging, but as a result of aging, which precipitates the aging process through a feedback loop, leading to further diseases of aging. The feedback loop consists of stress induced corticosterone hypersecretion leading to neural receptor loss that leads to more corticosteron secretion. The feedback loop then precipitates the release of a cascade of hormones that lead to concomitant conditions which include Immunosuppression, Muscle Atrophy, Osteoporosis, Hyperglycemia, Arteriosclerosis, and Steroid Diabetes. Sapolsky et al. conclude their paper suggesting that stress induced glucorticords affect the rate of aging and "may also influence the capacity to withstand acute neuropathological insults." It is our hope that the research described here will aid in understanding and tempering the excesses of aging which each of us must inevitably face. http://science-of-aging.healthaliciousness.com/timelines/glucocorticoid-cascade-hypothesis.php Wed, 24 Jun 2009 20:49:27 MST http://science-of-aging.healthaliciousness.com/timelines/johnson-friedman-define-age-1-gene.php With long-lived strains of mutant nematodes C elegans being identified Thomas Johnson and David Friedman set out to define which genes in the mutant worms were responsible for the increase in life span. Their idea was to obtain the different long-lived strains and cross them to see which alleles had an effect and which didn't. Their results yielded alleles: MK31, MK542, and MK546 which they deemed the age-1 gene.While the identification of these alleles was exciting, the mutants also expressed decreased sexual function, a finding which supports the theory of antagonistic plieotropy. In short, the theory suggests most favorable mutations to reproduction also carry a negative effect. In Johnson and Friedman's words: Most mutational events results in lower viability and decreased life expectancy. The shorter life span of most mutants is not surprising since species have undergone extensive selective adaptation of life history characteristics to maximize reproductive success. Philosophy aside, Friedman and Johnson's discovery helped set the stage for identifying molecular mechanisms leading to longer life."It is of considerable interest to know whether other mutations at other loci in C. elegans can lead to longer life."A prelude of things to come indeed. http://science-of-aging.healthaliciousness.com/timelines/johnson-friedman-define-age-1-gene.php Wed, 17 Jun 2009 13:58:58 MST http://science-of-aging.healthaliciousness.com/timelines/greider-blackburn-discover-telomerase.php In 1985 Elizabeth H. Blackurn and Carol W. Greider set out to find a model of terminal transferase-like activity which could add telomeric repeats to a host cell. The idea that such a model existed was proposed a year earlier by Shampay, Szostak, and Blackburn.2 Blackburn and Greider noticed that mated Tetrahymena undergoing macronuclear development fragmented their chromosomes into more than 200 pieces and new telomeres were then generated at the ends of the fragments. Their idea was then to compare extracts from these cells to Tetrahymena cells undergoing normal vegetative growth. Using a single-stranded DNA oligomer as a primer to assay telomere length, Blackburn and Greider found that the extracts of Tetrahymena undergoing macronuclear development indeed caused telomere elongation. Their discovery proved to be of profound significance, not just in showing that telomere length could be extended de novo, but also for suggesting a model as to how telomeres might be elongated. http://science-of-aging.healthaliciousness.com/timelines/greider-blackburn-discover-telomerase.php Wed, 10 Jun 2009 13:34:53 MST http://science-of-aging.healthaliciousness.com/timelines/sinclair-howitz-resveratrol.php Working off a model of calorie restriction via sirtuins David Sinclair et al. worked to find molecules which could modulate sitruins activity, and thus longevity. They accomplished this by screening a number of small molecule libraries, which included analogues of epsilon-acetyl lysine, NAD+, NAD+ precursors, nucleotides and purinergic ligands. Results from the screening where assayed against human SIRT1 to identify potential inhibitors, and the following molecules where found: Resveratrol, Butein, Piceatannol, Isoliquiritigenin, Fisetin, and Quercetin. Of all of these, resveratrol proved to be the most potent, increasing the replicative lifespan of yeast by 70%. It was not the only compound which extended yeast lifespan however, as butein increased it by 31%, and fisetin by 55%. Citing work which suggests SIR2 may extend lifespan by stabilizing repetitive DNA, the authors hypothesize that resveratrol works in the same way. "Homologous recombination between ribosomal DNA (rDNA) repeats can generate an extrachromosomal circular DNA molecule that is replicated until it reaches toxic levels in old cells. Consistent with this, resveratrol reduced the frequency of rDNA recombination by about 60% in a SIR2-dependent manner." The authors conclude the paper suggesting that their findings create new avenues of research for the effects of polyphenols on human aging and age related diseases. http://science-of-aging.healthaliciousness.com/timelines/sinclair-howitz-resveratrol.php Wed, 03 Jun 2009 19:31:51 MST http://science-of-aging.healthaliciousness.com/timelines/orgel-error-catastrophe.php Fidelity of protein translation is likely to be much lower than the fidelity of DNA replication -- in other words, translation introduces errors into individual proteins at a much higher rate than replication introduces mutations into DNA. Orgel considers two types of proteins: those involved in metabolism, and those involved in information processing. For metabolic proteins, translational error isn't a long-term problem for the cell, since a malfunctioning protein is simply one of many. Likewise, for translational errors causing loss of function in information processing proteins: the error isn't heritable, and a small decrease in the efficiency of gene expression is unlikely to pose a serious problem. However, information processing proteins can be altered in another way: by mutations that decrease the fidelity with which they process or propagate genetic information. Lower-fidelity transcription and translation will result in more mutations. This is the core of Orgel's idea: "errors which lead to a reduced specificity of an information-handling enzyme lead to an increasing error frequency. Such processes are clearly cumulative and...in the absence of an imposed selection for "accurate" protein-synthesizing units, must lead ultimately to an error catastrophe; that is, the error frequency must reach a value at which one of the processes necessary for the existence of viable cell becomes critically inefficient." Orgel then proceeded to ask whether such a phenomenon could play a role in the aging process. At the time, there was not sufficient evidence to draw a conclusion, and Orgel is careful not to overstep: "I wish to make it clear that I am not proposing here that the accumulation of protein transcription errors is the mechanism of ageing. My object is the more modest one of pointing out one source of progressive deterioration of cells and cell lines. Since I am unable to estimate the time scale of this process, I can only suggest experiments which should show where, if anywhere, it contributes to the ageing process in higher organisms." (The above should be considered an outline of Orgel's logic and conclusions. The error catastrophe did not withstand experimental testing, but it was nonetheless influential and therefore represents an important contribution to theories of aging.) http://science-of-aging.healthaliciousness.com/timelines/orgel-error-catastrophe.php Thu, 28 May 2009 17:12:15 MST http://science-of-aging.healthaliciousness.com/timelines/life-span-tor-sch9.php In 2005 Kaeberlein et al. published a paper suggesting that the mechanism for calorie restriction is via the TOR1 Sch9 pathways, independent of the Sir2 pathway. Kaeberlein et al. reached their conclusion via analysis 564 gene deletion strains of yeast. The strains were then classified as follows: Mean life span less than 20 generations are short lived (SL) Mean life span less than 26 generations are not long lived (NLL) Mean life span more than 36 generations are long lived (LL) Out of the 564 gene deleted strains 44 were initially classified as long lived (LL), and out of the 44, 13 were classified as statistically significant in extending lifespan. Further, of the 13 genes classified as significant all showed reduced expression of FOB1, a known pathway of increasing longevity, which helped to confirm the assay. The resultant deletion strains showed that decreased expression of TOR1, protein kinase A (PKA), and Sch9 all increased replicative life-span. TOR1 is thought to run upstream and parallel to PKA and Sch9. All three mechanisms regulate common downstream targets such as ribosomal proteins Rp131a and Rp16b. Since it has been shown that orthologs of TOR1 and Sch9 in Caenorhabditis elegans and Drosophila melanogaster regulate lifespan, the authors conclude that the reduced activity of TOR1 and Sch9 presents "a model whereby CR increases life span through a highly conserved, Sir2-independent signaling network from nutrients to ribosomes." http://science-of-aging.healthaliciousness.com/timelines/life-span-tor-sch9.php Wed, 27 May 2009 07:18:17 MST http://science-of-aging.healthaliciousness.com/timelines/murphy-downstream-daf-16.php While serving a post-doc with Cynthia Kenyon, Coleen Murphy et. al, discovered genes downstream of daf-16 and daf-2 which regulate aging in C.elegans nematodes. Murphy's approach compared long-lived mutants of C.elegans vs. wild type and collected gene expression data from the animals of various ages to also compare expression of different genes throughout development. 60 microarrays were collected in total and combined into a single set for hierarchical clustering and comparative analysis. The results found two groups of genes which appear to play a role in C.elegans longevity. The first set of genes appeared to function in terms of repairing oxidative and other macromolecular damage. The second set encoded antimicrobial lysosomes. The lysosomes could help to prevent bacterial packing which has been shown to increase with C.elegans age, and eventually kills the nematodes. In an additional analysis, Murphy then used the data to look for short sequences occurring in a statistical distribution that suggests they code meaningful information. Searching for sequences in this way is known as the Mobydick algorithm. The anaylsis uncovered over-represented expression of sequence T(G/A)TTTAC, which is known to be bound to daf-16 in vitro. A further sequence CTTATCA was found, which suggests daf-16 could be expressed in new unidentified pathways. Murphy concludes that the insulin/IGF-I signalling pathway regulates aging in C.elegans via several global regulators, involving many genes. "Longevity must have evolved not just once, but many times. Insect lifespans range from a few weeks to several years, and those of mammals (and also birds) range from a few years to a century." The study also found new unidentified proteins regulated by daf-16, opening doors for new potential regulators. In addition, the study confirmed that daf-16 encodes proteins protecting or reparing cells from oxidative/macromolecular damage. "Thus our study provides strong support for the theory that genes that increase resistance to environmental stress contribute to longevity." Finally, Murphy adds her own evolutionary theory to aging, stating that since the IGF system can independently regulate multiple life history functions: longevity, reproduction, states of dipause, and body size, it is favorable to foster evolution into environmental niches. http://science-of-aging.healthaliciousness.com/timelines/murphy-downstream-daf-16.php Mon, 18 May 2009 18:01:10 MST http://science-of-aging.healthaliciousness.com/timelines/cerami-maillard-aging.php Cerami's study on the effect of reducing sugars with long lived proteins in the body stems from "error catastrophe" theories of aging which state that accumulated damage to DNA leads to functional decline and cellular senescence. Cerami cites other sources of DNA damage theories stating: "Age-dependent changes in the genetic material are well documented and include increased tumorigenesis, chromosomal aberration, DNA strand breaks, and decreases in DNA repair, replication, and transcription." Cerami et al. reached their conclusion by incubating isolated DNA with high levels of glucose at 37 degrees Celsius, or body temperature, and recording changes in DNA through spectroscopy. "During incubation, absorbance and fluorescence changes develop that suggest that DNA can be glycosylated and undergo nonenzymatic browning." The fact that Cerami conducted his study out of the body, and even out of the cell, casts doubt on conclusion, and even Cerami admits That "Evaluating the significance of our findings to cellularphysiology must be done with caution." "The observation that an intracellular metabolite can modify DNA suggests a mechanism for the accumulation of genetic lesions that may lead to cellular senescence." Cerami backs his observations citing prior evidence of increased cross linking of proteins to DNA found in chromatin of aged organisms, however, he balances this thought citing evidence that proteins bound to DNA may in fact serve a protective role, and that any DNA damage by maillard products in vivo could be repaired via enzymatic mechanisms. http://science-of-aging.healthaliciousness.com/timelines/cerami-maillard-aging.php Sun, 10 May 2009 20:14:52 MST http://science-of-aging.healthaliciousness.com/timelines/bodnar-telomerase-sea-urchins.php Sea urchins have a long history as a model organism in developmental biology. Interestingly life-span varies between species. L. variegatus lives for only 3-4 years while S. franciscanus can live for more than 100. Bodnar et al. analyzed a wide array of tissues at various stages of development to measure for telomerase activity and found no difference in telomerase levels. The result suggests that telomere shortening might not be associated with increasing age. Bodnar also found that very old sea urchins with telomerase activity did not experience neoplastic transformation (cancer) suggesting that a decline in telomerase does not serve as a cancer suppressor. Bodnar will continue to search for genetic factors contributing to the difference of lifespan between the two species of sea urchins applying results to an understanding of aging and resistance age-related diseases. http://science-of-aging.healthaliciousness.com/timelines/bodnar-telomerase-sea-urchins.php Tue, 05 May 2009 18:00:06 MST http://science-of-aging.healthaliciousness.com/timelines/extension-of-life-span-telomerase.php Andrea Bodnar, Michel Ouellette, et al. Find that introduction of telomerase into human cells extends cell life-span http://science-of-aging.healthaliciousness.com/timelines/extension-of-life-span-telomerase.php Fri, 01 May 2009 12:59:07 MST http://science-of-aging.healthaliciousness.com/timelines/hayflick-moorhead-senescence-telomeres.php Leonard Hayflick characterizes cellular senescence in primary human cells http://science-of-aging.healthaliciousness.com/timelines/hayflick-moorhead-senescence-telomeres.php Wed, 29 Apr 2009 21:33:51 MST http://science-of-aging.healthaliciousness.com/timelines/williams-antagonistic-pleiotropy.php George C. Williams expands on the theory of antagonistic pleiotropy http://science-of-aging.healthaliciousness.com/timelines/williams-antagonistic-pleiotropy.php Mon, 20 Apr 2009 21:29:57 MST http://science-of-aging.healthaliciousness.com/timelines/soa-timeline-references.php The science of aging timeline has been presented in a listed view, highlighting only the discovery and the relevent references. http://science-of-aging.healthaliciousness.com/timelines/soa-timeline-references.php Wed, 15 Apr 2009 11:42:46 MST http://science-of-aging.healthaliciousness.com/timelines/medawar-theory-mutation-accumulation.php Peter Medawar proposes that aging evolved into existence since the force of natural selection diminishes after reproduction http://science-of-aging.healthaliciousness.com/timelines/medawar-theory-mutation-accumulation.php Tue, 14 Apr 2009 22:02:56 MST http://science-of-aging.healthaliciousness.com/timelines/harman-free-radical-theory.php Denham Harman proposes the free radical theory of aging http://science-of-aging.healthaliciousness.com/timelines/harman-free-radical-theory.php Fri, 27 Mar 2009 19:57:56 MST http://science-of-aging.healthaliciousness.com/timelines/hayflick-cells-limited-lifespan.php Leonard Hayflick discovers that untransformed human cells in culture have a limited replicative lifespan http://science-of-aging.healthaliciousness.com/timelines/hayflick-cells-limited-lifespan.php Thu, 26 Mar 2009 15:12:02 MST http://science-of-aging.healthaliciousness.com/timelines/no-sensescence-in-hydra.php Daniel E. Martinez proves that hydra do not age http://science-of-aging.healthaliciousness.com/timelines/no-sensescence-in-hydra.php Thu, 26 Mar 2009 13:43:07 MST http://science-of-aging.healthaliciousness.com/timelines/golgi-discovers-the-golgi-apparatus.php Camillo Golgi discovers the Golgi apparatus http://science-of-aging.healthaliciousness.com/timelines/golgi-discovers-the-golgi-apparatus.php Sat, 07 Mar 2009 22:44:31 MST http://science-of-aging.healthaliciousness.com/timelines/hooke-history-cell-discovery.php Robert C. Hooke discovers the cell http://science-of-aging.healthaliciousness.com/timelines/hooke-history-cell-discovery.php Tue, 10 Mar 2009 07:28:37 MST http://science-of-aging.healthaliciousness.com/timelines/robert-remak-membrane-cell-division.php Robert Remak develops a method to isolate the cell membrane and proves it divides a cell http://science-of-aging.healthaliciousness.com/timelines/robert-remak-membrane-cell-division.php Mon, 23 Mar 2009 10:17:58 MST http://science-of-aging.healthaliciousness.com/timelines/theodor-schwann-all-life-composed-of-cells.php Theodor Schwann proposes that all living things are entirely made of cells http://science-of-aging.healthaliciousness.com/timelines/theodor-schwann-all-life-composed-of-cells.php Mon, 23 Mar 2009 10:10:50 MST http://science-of-aging.healthaliciousness.com/timelines/virchow-pathology-cell-formation.php Rudolf Virchow endorses cell division and its role in pathology http://science-of-aging.healthaliciousness.com/timelines/virchow-pathology-cell-formation.php Mon, 23 Mar 2009 10:28:17 MST http://science-of-aging.healthaliciousness.com/timelines/yeast-daughter-cells-shortened-lifespan.php Brian K. Kennedy discovers that the daughter cells of old yeast have shorter life-spans than those of younger strains. http://science-of-aging.healthaliciousness.com/timelines/yeast-daughter-cells-shortened-lifespan.php Thu, 26 Mar 2009 21:53:59 MST http://science-of-aging.healthaliciousness.com/timelines/robert-brown-names-cell-nucleus.php Robert Brown names the cell nucleus and suggests its importance in fertilization http://science-of-aging.healthaliciousness.com/timelines/robert-brown-names-cell-nucleus.php Mon, 23 Mar 2009 08:48:13 MST http://science-of-aging.healthaliciousness.com/timelines/gompertz-aging-human-mortality.php Benjamin Gompertz finds that mortality increases exponentially with age http://science-of-aging.healthaliciousness.com/timelines/gompertz-aging-human-mortality.php Wed, 18 Mar 2009 20:59:23 MST http://science-of-aging.healthaliciousness.com/timelines/guarente-sir4-delay-yeast-aging.php Brian K. Kennedy finds that SIR4-42 extends the life span of yeast by 30% and may play a key role in preventing agin. http://science-of-aging.healthaliciousness.com/timelines/guarente-sir4-delay-yeast-aging.php Thu, 26 Mar 2009 21:54:34 MST http://science-of-aging.healthaliciousness.com/timelines/clive-mccay-prolonging-lifespan-caloric-restriction.php Clive M. McCay discovers that rats on a calorie restricted diet can live twice as long http://science-of-aging.healthaliciousness.com/timelines/clive-mccay-prolonging-lifespan-caloric-restriction.php Mon, 23 Mar 2009 08:38:58 MST http://science-of-aging.healthaliciousness.com/timelines/kenyon-elegans-mutant-lives-twice-as-long.php Cynthia Kenyon finds that mutations in daf-2 and daf-16 genes cause C. elegans worms to live over twice as long. http://science-of-aging.healthaliciousness.com/timelines/kenyon-elegans-mutant-lives-twice-as-long.php Thu, 26 Mar 2009 21:23:48 MST http://science-of-aging.healthaliciousness.com/timelines/rose-evolution-animal-senescence.php Michael R. Rose asserts that senescence can be postponed by natural selection http://science-of-aging.healthaliciousness.com/timelines/rose-evolution-animal-senescence.php Thu, 26 Mar 2009 21:30:48 MST http://science-of-aging.healthaliciousness.com/timelines/leeuwenhoek-sees-the-cell-nucleus.php Antoni Van Leeuwenhoek sees blood cells and describes the cell nucleus http://science-of-aging.healthaliciousness.com/timelines/leeuwenhoek-sees-the-cell-nucleus.php Sat, 21 Mar 2009 20:21:05 MST http://science-of-aging.healthaliciousness.com/timelines/sharpless-ink4a-arf-locus-senescence.php Norman E. Sharpless finds that expression of the Ink4a/Arf locus is a biomarker of aging http://science-of-aging.healthaliciousness.com/timelines/sharpless-ink4a-arf-locus-senescence.php Thu, 26 Mar 2009 21:48:39 MST http://science-of-aging.healthaliciousness.com/timelines/walford-middle-age-dietary-restriction-lifespan-cancer.php Richard Weindruch finds that adult mice on dietary restriction live 20% longer and have lower cancer rates http://science-of-aging.healthaliciousness.com/timelines/walford-middle-age-dietary-restriction-lifespan-cancer.php Thu, 26 Mar 2009 21:26:43 MST http://science-of-aging.healthaliciousness.com/timelines/goldstein-replicative-senescence.php Samuel Goldstein proposes that the activation of specific genes is the cause of cellular aging http://science-of-aging.healthaliciousness.com/timelines/goldstein-replicative-senescence.php Tue, 24 Mar 2009 11:33:24 MST