http://www.gopubmed.org/web/gopubmed/2?WEB0qns0czvots8yI4kI1I00f01000j10040001rl chromosomes ends and longevity 19 documents semantically analyzed Top Years Publications 2008 3 2005 3 2003 3 2009 2 2006 2 2002 2 2007 1 2004 1 2000 1 1996 1 Top Countries Publications USA 8 Canada 2 Austria 2 Australia 2 Japan 1 France 1 Italy 1 Top Cities Publications Wien 2 San Francisco 1 Irvine 1 Dallas 1 Gainesville 1 Montreal 1 Ames 1 San Antonio 1 Paris 1 North Chicago 1 Messina 1 Sydney 1 Top Journals Publications Ann N Y Acad Sci 1 B Acad Nat Med Paris 1 Lik Sprava 1 Mech Ageing Dev 1 Mol Biol Evol 1 Chromosoma 1 Mol Ecol 1 Pathology 1 J Am Geriatr Soc 1 Biogerontology 1 Mol Cell 1 Med Hypotheses 1 Metabolism 1 P Roy Soc Lond B Bio 1 Sci Aging Knowledge Environ 1 J Mal Vascul 1 Gerontology 1 Int J Oncol 1 Bioessays 1 1 2 3 Top Authors Publications Haussmann M 2 Blackburn E 1 Ardaillou R 1 Legall J 1 Osipov N 1 Autexier C 1 Shawi M 1 Mauck R 1 Biessmann H 1 Walter M 1 Biessmann M 1 Benitez C 1 Trk T 1 Mason J 1 Blomqvist D 1 Pauliny A 1 Wagner R 1 Augustn J 1 Szp T 1 Lee C 1 1 2 3 1 2 3 ... 18 Top Terms Publications Telomere 19 chromosome, telomeric region 19 Longevity 18 Aging 15 Chromosomes 14 Cell Aging 13 Humans 13 DNA 13 Animals 10 Telomerase 10 senescence 10 cell aging 9 Cell Division 7 positive regulation of telomerase activity 6 regulation of telomerase activity 6 chromosome 6 telomere capping 5 telomerase inhibitor activity 5 negative regulation of telomerase activity 5 telomerase activity 5 1 2 3 ... 18 http://www.sciencenet.cn/htmlnews/2009/12/226136.shtm 丹麦研究发现：长娃娃脸者可以长寿 从脸上就可看出你是否长寿。 据英国《每日邮报》12月14日报道，南丹麦大学的凯尔克里斯滕森教授最近指出，长着一张娃娃脸的人意味着他/她将享受更长的寿命，因为人们的生活状况很容易反映在脸上。 凯尔教授领导的研究小组以双胞胎为研究对象，看看外表年龄(也就是别人认为你有多大)与你的生存能力、身体机能和智力有着何种联系。这项研究始于2001年春季开始，研究者对1826对70岁以上的丹麦双胞胎进行了体能和认知测试，并拍了他们的面部照片。三名评审员在不知道他们年龄范围的情况下对不同年龄组的双胞胎进行年龄评估，结果发现，即使是双胞胎，被猜出的年龄也相差很大。研究者然后用7年时间对这些双胞胎的晚年生活进行了跟踪调查，直至他们去世。调查表明：双胞胎中，外表年龄差异越大，看起来老的那个就越有可能先死。该研究报告发表在《英国医学杂志》（ BMJ ）上。 凯尔教授还研究了寿命是否与染色体终端有关，发现染色体的状态与生命老化有直接关系，就如同鞋带末端上的塑料帽一样，这些染色体末端由于细胞分裂而不断损耗，这是一个自然老化的进程。染色体上端粒较短的人更容易患上与年龄增长相关的病症，死亡时间也会更早。端粒较长意味着你更年轻、更健康。但他认为端粒测试太复杂，不如看外表来得简单。外表年龄是每个人生活环境、性生活、生活状况和心态的集中体现。 更多阅读 英国《每日邮报》相关报道（英文） http://www.dailymail.co.uk/sciencetech/article-1235639/Are-baby-face-Then-youll-live-ripe-old-age.html Are you a baby face? Then you'll live to a ripe old age By Jenny Hope Last updated at 10:01 AM on 14th December 2009 Comments ( 50 ) Add to My Stories People who look young for their age are already the envy of their peers. But those holding back the years haven't just been blessed in the looks department. Scientists have shown that looking younger than you are also means you will enjoy a longer life. Not only do the wrinkles remain at bay, but the Grim Reaper takes longer to call, according to researchers. Fresh faced: Cliff Richard has managed to hold on to his youthful appearance They suggest patients could give their GPs a photo of themselves for their medical records as this would be as good a guide to their longevity as complicated testing. Professor Kaare Christensen, from the University of Southern Denmark, set out to test the belief that a person's perceived age gives a general indication of his health. His team looked at twins to see whether perceived age - basically how old others think you are - is linked with survival, as well as important age-related traits such as physical functioning and brainpower. The researchers also examined evidence relating to chromosomes and DNA and their effect on longevity. But in the end, it seems, the best method of research was simply a long hard look in the mirror. More... How a healthy human heart follows same beauty ratio as George Clooney 'It's probably easy to explain because people who've had a tougher life are more likely to die early - and their life is reflected in their face,' Professor Christensen said. The research started back in spring 2001, when 1,826 Danish twins aged 70 years and over underwent physical and cognitive tests and had their faces photographed. Three groups of assessors rated the perceived age of the twins from the photographs. The assessors did not know the age range of the twins, and each twin of a pair had their age assessed on different days. Death records were then used to track the survival of the twins over a seven-year period, say findings published on the British Medical Journal website bmj.com. Perceived age was significantly associated with survival, even after adjusting for chronological age, sex, and the environment in which each pair of twins grew up. The bigger the difference in perceived age within a twin pair, the more likely it was that the olderlooking twin died first. Professor Christensen also investigated whether longevity was linked to the length of telomeres, which are tiny 'caps' on the ends of chromosomes that protect the strands of DNA from inflammation and other ageing processes. Longer telomeres are a sign of being biologically younger and also of being healthier. He dismissed the telomere tests as complicated and only helping establish a weak link with longevity. Far better, he said, to simply look at a person's face. And what if that face has a been tweaked a little by the cosmetic surgeon? Professor Christensen said such surgery was uncommon in the part of Denmark where the study was carried out, so was not a major factor. Comments ( 50 ) Here's what readers have had to say so far. Why not add your thoughts below, or debate this issue live on our message boards. The comments below have not been moderated. Newest Oldest Best rated Worst rated View all For those of you who look younger then your real age, take heart at age 62 people think I'm in my late 40's. Secretly I love it, but my wife of 40 years finds it annoying when people think she is much older than me when in fact she is 3 years younger. - Bob M., Westwood, New Jersey, USA, 14/12/2009 23:02 Click to rate Rating 1 Report abuse Another rubbish statement. My husband never looked his age. When we married I was 21 he was 37 but most people thought he was in his 20's. He died of cancer before his 74th birthday. Not old by any standards. - Jean, Kinross Scoland, 14/12/2009 21:36 Click to rate Rating (0) Report abuse There's hope for me yet! At 31 not one person has said I look my age - more like 20-23 years of age!!! I've just had a 20-year-old student for a few weeks and many said he looked older than me! - Sue, Yorkshire, 14/12/2009 20:45 Click to rate Rating (0) Report abuse I think Cliff has had more than a little assistance to maintain that youthful appearance. - Michelle, Pioneertown, California, 14/12/2009 19:49 Click to rate Rating 12 Report abuse Maybe Cliff being loaded and having a stress free life is the reason he looks so young. - Wan King, London, 14/12/2009 19:41 Click to rate Rating 8 Read more: http://www.dailymail.co.uk/sciencetech/article-1235639/Are-baby-face-Then-youll-live-ripe-old-age.html#ixzz0ZilL2ZB5 相关研究论文19篇： PMID- 19735238 OWN - NLM STAT- MEDLINE DA - 20090908 DCOM- 20090925 IS - 1749-6632 (Electronic) VI - 1172 DP - 2009 Aug TI - Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres. PG - 34-53 AB - Understanding the malleable determinants of cellular aging is critical to understanding human longevity. Telomeres may provide a pathway for exploring this question. Telomeres are the protective caps at the ends of chromosomes. The length of telomeres offers insight into mitotic cell and possibly organismal longevity. Telomere length has now been linked to chronic stress exposure and depression. This raises the question of mechanism: How might cellular aging be modulated by psychological functioning? We consider two psychological processes or states that are in opposition to one another-threat cognition and mindfulness-and their effects on cellular aging. Psychological stress cognitions, particularly appraisals of threat and ruminative thoughts, can lead to prolonged states of reactivity. In contrast, mindfulness meditation techniques appear to shift cognitive appraisals from threat to challenge, decrease ruminative thought, and reduce stress arousal. Mindfulness may also directly increase positive arousal states. We review data linking telomere length to cognitive stress and stress arousal and present new data linking cognitive appraisal to telomere length. Given the pattern of associations revealed so far, we propose that some forms of meditation may have salutary effects on telomere length by reducing cognitive stress and stress arousal and increasing positive states of mind and hormonal factors that may promote telomere maintenance. Aspects of this model are currently being tested in ongoing trials of mindfulness meditation. AD - University of California San Francisco, Department of Psychiatry, San Francisco, California 94143, USA. eepel@lppi.ucsf.edu FAU - Epel, Elissa AU - Epel E FAU - Daubenmier, Jennifer AU - Daubenmier J FAU - Moskowitz, Judith Tedlie AU - Moskowitz JT FAU - Folkman, Susan AU - Folkman S FAU - Blackburn, Elizabeth AU - Blackburn E LA - eng GR - R56-AG030424/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 SB - IM MH - Adaptation, Psychological/physiology MH - Cell Aging/*genetics MH - Cognition/physiology MH - Humans MH - *Meditation MH - Stress, Psychological/*physiopathology MH - Telomere/*genetics RF - 144 EDAT- 2009/09/09 06:00 MHDA- 2009/09/26 06:00 CRDT- 2009/09/09 06:00 AID - NYAS4414 AID - 10.1111/j.1749-6632.2009.04414.x PST - ppublish SO - Ann N Y Acad Sci. 2009 Aug;1172:34-53. PMID- 19718893 OWN - NLM STAT- MEDLINE DA - 20090901 DCOM- 20090929 IS - 0001-4079 (Print) VI - 193 IP - 2 DP - 2009 Feb TI - PG - 365-402; discussion 402-4 AB - Although aging is unavoidable, its course can be influenced by various factors, as illustrated by the increase in life expectancy associated with improvements in hygiene and with the general reduction in morbidity. Longevity has also been altered experimentally in some animal species. Aging follows a period of growth and reproduction. Death may occur when the immortality of the germinal line has been ensured. In other cases it results from gradual cellular deterioration. Four principal molecular and cellular processes have been studied in experimental models (mainly mice, worms and fruit flies):--inhibition of the insulin/IGF-1 axis increases life expectancy by allowing a transcription factor (DAF-16 in C. elegans, FoXo in mice) to enter the nucleus, where it stimulates the expression of genes encoding survival-promoting proteins; one such inhibitor is Klotho protein;--the detrimental effects of highly toxic reactive oxygen species, mainly produced in the mitochondria, are partly controlled by scavenging molecules and enzymes. Their accumulation leads to DNA, lipid and protein changes, resulting in cell dysfunction;--the telomeres situated at the ends of each chromosome get shorter with time because of inadequate telomerase activity, and this appears to be associated with diminished longevity;--autophagia within lysosomes destroys altered proteins and thereby maintains cell homeostasis. However, this activity diminishes with time, resulting in the accumulation of toxic metabolites in the cell, dysfunction of the endoplasmic reticulum and mitochondria, and increased apoptosis. Studies of genetically mediated aging disorders have revealed the importance of lamins (intermediate nuclear filaments). For example, a mutation that prevents the protein lamin A from maturing is the cause of progeria, a disease associated with an acceleration of most aging processes and with premature death. There is no single biological marker of aging. In contrast, a combination of Nt-proBNP, troponin I, C-reactive protein and cystatin may be useful, as increased levels are a risk factor for atheroma and cardiovascular diseases, both of which are associated with aging. The different organs age in different ways: vessel walls become rigid due to protein glycation and develop atheroma; the heart is invaded by fibrosis; the brain suffers from neurofibrillar degeneration and senile plaques (responsible for Alzheimer's disease); the retina undergoes macular degeneration; renal function declines in parallel with the fall in the glomerular filtration rate due to a gradual decrease in the nephron pool; and immune defenses become less effective due to the functional degradation of B and T lymphocytes and thymus involution. Reproduction is a special case: despite the increase in human longevity, the chronology of the reproductive cycle and the age of menopause onset have not changed. The frequency of cancers increases with age, due to the increase in somatic mutations and the decline in immune defenses. Drug therapy must be adapted to age, owing to age-related changes in pharmacology. Physical exercise and dietary measures are currently the only known ways of slowing the aging process. FAU - Le Gall, Jean-Yves AU - Le Gall JY FAU - Ardaillou, Raymond AU - Ardaillou R LA - fre PT - English Abstract PT - Journal Article TT - Biologie du vieillissement. PL - Netherlands TA - Bull Acad Natl Med JT - Bulletin de l'Academie nationale de medecine JID - 7503383 RN - 0 (Reactive Oxygen Species) RN - 11061-68-0 (Insulin) RN - 67763-96-6 (Insulin-Like Growth Factor I) SB - IM MH - Aging/*physiology MH - Animals MH - Autophagy/physiology MH - Humans MH - Insulin/physiology MH - Insulin-Like Growth Factor I/physiology MH - Longevity/physiology MH - Lysosomes/metabolism MH - Reactive Oxygen Species/metabolism MH - Telomere EDAT- 2009/09/02 06:00 MHDA- 2009/09/30 06:00 CRDT- 2009/09/02 09:00 PST - ppublish SO - Bull Acad Natl Med. 2009 Feb;193(2):365-402; discussion 402-4. PMID- 19145831 OWN - NLM STAT- MEDLINE DA - 20090116 DCOM- 20090309 IS - 1019-5297 (Print) IP - 3-4 DP - 2008 Apr-Jun TI - PG - 110-2 AB - Telomeres are the ends of chromosomes and are non-coding DNA end-capped with structures containing DNA-quadruplexes and proteins. Telomeres become shorter after each cell division, which is one of the mechanisms of gradual ageing. Telomerase is the reverse transcriptase responsible for the extension of telomere length. It is well known that activation of telomerase in the most types of organism's cells is not enough for telomere length stabilization. The reason may be in the telomere caps, which cover telomere ends from telomerase action. This experiment shows that telomeres were elongated by the combination of hypoxia activated telomerase and a newly developed pharmacological method removing the telomere cap when this combined method was applied to the human lymphocyte culture and the Wistar rats. Rats from the control group died at the age 1 year 7 month - 1 year 8 month, which is typical for the Wistar rats from our sub-line. Rats from the experimental group died at the age 2 year 4 month. The result Morris's labyrinth water test showed the better spatial memory function of rats passed the telomere stabilization therapy. The results of these experiments show the significant role of telomere stabilization therapy in prolongation of lifespan. FAU - Osipov, N V AU - Osipov NV LA - rus PT - English Abstract PT - Journal Article PL - Ukraine TA - Lik Sprava JT - Likars'ka sprava / Ministerstvo okhorony zdorov'ia Ukrainy JID - 9601540 RN - 0 (Telomere-Binding Proteins) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Animals MH - Anoxia/physiopathology MH - Cells, Cultured MH - Enzyme Activation MH - Hair/growth development MH - Humans MH - Longevity/*genetics/physiology MH - Lymphocytes/enzymology/metabolism/*ultrastructure MH - Maze Learning/physiology MH - Memory/physiology MH - Rats MH - Rats, Wistar MH - Spatial Behavior/physiology MH - Telomerase/metabolism MH - Telomere/enzymology/metabolism/*ultrastructure MH - Telomere-Binding Proteins/*metabolism EDAT- 2009/01/17 09:00 MHDA- 2009/03/10 09:00 CRDT- 2009/01/17 09:00 PST - ppublish SO - Lik Sprava. 2008 Apr-Jun;(3-4):110-2. PMID- 18215413 OWN - NLM STAT- MEDLINE DA - 20080303 DCOM- 20080403 IS - 0047-6374 (Print) VI - 129 IP - 1-2 DP - 2008 Jan-Feb TI - Telomerase, senescence and ageing. PG - 3-10 AB - Telomeres serve to camouflage chromosome ends from the DNA damage response machinery. Telomerase activity is required to maintain telomeres. One consequence of telomere dysfunction is cellular senescence, a permanent growth arrest state. We review the key regulators of cellular senescence and recent in vivo evidence which supports p53-dependent senescence induced by short telomeres as a potent tumor suppressor pathway. The in vivo link between cellular senescence and tumor regression is also discussed. The relationship between short telomere length and ageing or disease states in various cells of the body is increasingly reported. Paradoxically, the introduction of telomerase is proposed as a method to combat ageing via cell therapy and a possible method to regenerate tissue, while telomerase inhibition and telomere shortening is suggested as a possible therapy to defeat cancers with intact p53. Researchers thus face the challenge of understanding the complex processes which regulate the potential benefits of both telomerase inhibition and activation. AD - Department of Medicine, Division of Experimental Medicine, McGill University, Canada. FAU - Shawi, May AU - Shawi M FAU - Autexier, Chantal AU - Autexier C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20071214 PL - Ireland TA - Mech Ageing Dev JT - Mechanisms of ageing and development JID - 0347227 RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Aging/*genetics MH - *Cell Aging/genetics MH - Humans MH - Longevity MH - Telomerase/genetics/*metabolism MH - Telomere/chemistry/metabolism RF - 95 EDAT- 2008/01/25 09:00 MHDA- 2008/04/04 09:00 CRDT- 2008/01/25 09:00 PHST- 2007/09/14 PHST- 2007/11/23 PHST- 2007/11/30 PHST- 2007/12/14 AID - S0047-6374(07)00180-7 AID - 10.1016/j.mad.2007.11.007 PST - ppublish SO - Mech Ageing Dev. 2008 Jan-Feb;129(1-2):3-10. Epub 2007 Dec 14. PMID- 18071200 OWN - NLM STAT- MEDLINE DA - 20080121 DCOM- 20080716 LR - 20081121 IS - 1537-1719 (Electronic) VI - 25 IP - 1 DP - 2008 Jan TI - Telomeres and longevity: testing an evolutionary hypothesis. PG - 220-8 AB - Identifying mechanisms that underlie variation in adult survivorship provide insight into the evolution of life history strategies and phenotypic variation in longevity. There is accumulating evidence that shortening telomeres, the protective caps at the ends of chromosomes, play an important role in individual variation in longevity. Given that telomeres generally shorten with age, it was surprising to find that in a population of a long-lived seabird, Leach's storm petrel, telomeres appear to lengthen with age. This unique finding suggested that the longest lived individuals are able to elongate telomeres, an interpretation we call the elongation hypothesis. Alternatively, the selection hypothesis states that the longest lived individuals start with the longest telomeres and variation in telomere length decreases with age due to the selective disappearance of individuals with short telomeres. In the same population in which evidence supporting both hypotheses was uncovered, we tested mutually exclusive predictions from the elongation and selection hypotheses by measuring telomere length with the telomere restriction fragment assay in hatchling and old, adult storm petrels. As previously found, adult birds had longer telomeres on average compared with hatchlings. We also found that 3 hatchlings had mean telomere lengths exceeding that of the most extreme old bird, old birds on average had longer initial telomere lengths than hatchlings, and the variance in mean telomere length was significantly greater for hatchlings than for old birds, all predicted by the selection hypothesis. Perhaps more surprisingly, the oldest adults also show little or no accumulation of short telomeres over time, a pattern unknown in other species. Long telomeres are thought to provide a buffer against cellular senescence and be generally indicative of genome stability and overall cell health. In storm petrels, because the progressive accumulation of short telomeres appears negligible, variation in telomere length at birth may be linked to individual variation in longevity. AD - Department of Biology, Kenyon College, Gambier, Ohio 43022, USA. haussmannm@kenyon.edu FAU - Haussmann, Mark F AU - Haussmann MF FAU - Mauck, Robert A AU - Mauck RA LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20071210 PL - United States TA - Mol Biol Evol JT - Molecular biology and evolution JID - 8501455 SB - IM MH - Animals MH - Birds/*genetics MH - Cell Aging/*genetics MH - Female MH - *Genetic Variation MH - Longevity/*genetics MH - Male MH - Telomere/*genetics EDAT- 2007/12/12 09:00 MHDA- 2008/07/17 09:00 CRDT- 2007/12/12 09:00 PHST- 2007/12/10 AID - msm244 AID - 10.1093/molbev/msm244 PST - ppublish SO - Mol Biol Evol. 2008 Jan;25(1):220-8. Epub 2007 Dec 10. PMID- 17089138 OWN - NLM STAT- MEDLINE DA - 20070126 DCOM- 20070713 LR - 20081120 IS - 0009-5915 (Print) VI - 116 IP - 1 DP - 2007 Feb TI - Effects of telomere length in Drosophila melanogaster on life span, fecundity, and fertility. PG - 41-51 AB - Chromosome length in Drosophila is maintained by targeted transposition of three non-long terminal repeat retrotransposons, HeT-A, TART, and TAHRE, to the chromosome ends. The length and composition of these retrotransposon arrays can vary significantly between chromosome tips and between fly stocks, but the significance and consequences of these length differences are not understood. A dominant genetic factor, Tel, has been described, which causes a severalfold elongation of the retrotransposon arrays at all telomeres. We used this strain to assess possible affects of extended telomeres on the organism. While we found no effect on life span of the adults, we could demonstrate a correlation between long telomeres and reduced fertility and fecundity in individual females, which is also reflected in abnormal oocyte development. AD - Developmental Biology Center, University of California, Irvine, CA 92697, USA. FAU - Walter, Marika F AU - Walter MF FAU - Biessmann, Max R AU - Biessmann MR FAU - Benitez, Cecil AU - Benitez C FAU - Torok, Tibor AU - Torok T FAU - Mason, James M AU - Mason JM FAU - Biessmann, Harald AU - Biessmann H LA - eng GR - GM-56729/GM/NIGMS NIH HHS/United States GR - Z01 ES021054-14/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20061107 PL - Germany TA - Chromosoma JT - Chromosoma JID - 2985138R RN - 0 (Chromosomal Proteins, Non-Histone) RN - 0 (Retroelements) RN - 107283-02-3 (heterochromatin-specific nonhistone chromosomal protein HP-1) SB - IM MH - Animals MH - Chromosomal Proteins, Non-Histone/genetics/metabolism MH - Drosophila melanogaster/*physiology MH - Female MH - Fertility/*genetics MH - Longevity/*genetics MH - Male MH - Mutation MH - Ovary/growth development/pathology MH - Retroelements/genetics MH - Telomere/*genetics PMC - PMC2254661 MID - NIHMS18974 OID - NLM: NIHMS18974 OID - NLM: PMC2254661 EDAT- 2006/11/08 09:00 MHDA- 2007/07/14 09:00 CRDT- 2006/11/08 09:00 PHST- 2006/04/28 PHST- 2006/08/28 PHST- 2006/07/29 PHST- 2006/11/07 AID - 10.1007/s00412-006-0081-5 PST - ppublish SO - Chromosoma. 2007 Feb;116(1):41-51. Epub 2006 Nov 7. PMID- 16629820 OWN - NLM STAT- MEDLINE DA - 20060424 DCOM- 20060616 LR - 20061115 IS - 0962-1083 (Print) VI - 15 IP - 6 DP - 2006 May TI - Age-independent telomere length predicts fitness in two bird species. PG - 1681-7 AB - Telomeres are dynamic DNA-protein structures that form protective caps at the ends of eukaryotic chromosomes. Although initial telomere length is partly genetically determined, subsequent accelerated telomere shortening has been linked to elevated levels of oxidative stress. Recent studies show that short telomere length alone is insufficient to induce cellular senescence; advanced attrition of these repetitive DNA sequences does, however, reflect ageing processes. Furthermore, telomeres vary widely in length between individuals of the same age, suggesting that individuals differ in their exposure or response to telomere-shortening stress factors. Here, we show that residual telomere length predicts fitness components in two phylogenetically distant bird species: longevity in sand martins, Riparia riparia, and lifetime reproductive success in dunlins, Calidris alpina. Our results therefore imply that individuals with longer than expected telomeres for their age are of higher quality. AD - Konrad Lorenz Institute for Ethology, Austrian Academy of Sciences, Vienna. FAU - Pauliny, Angela AU - Pauliny A FAU - Wagner, Richard H AU - Wagner RH FAU - Augustin, Jakob AU - Augustin J FAU - Szep, Tibor AU - Szep T FAU - Blomqvist, Donald AU - Blomqvist D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Mol Ecol JT - Molecular ecology JID - 9214478 SB - IM MH - Age Factors MH - Body Size MH - Charadriiformes/anatomy histology/*genetics/growth development MH - Longevity/*genetics MH - Phylogeny MH - Reproduction/*genetics MH - Swallows/anatomy histology/*genetics/growth development MH - Telomere/*chemistry EDAT- 2006/04/25 09:00 MHDA- 2006/06/17 09:00 CRDT- 2006/04/25 09:00 AID - MEC2862 AID - 10.1111/j.1365-294X.2006.02862.x PST - ppublish SO - Mol Ecol. 2006 May;15(6):1681-7. PMID- 16581649 OWN - NLM STAT- MEDLINE DA - 20060403 DCOM- 20060608 LR - 20061115 IS - 0031-3025 (Print) VI - 38 IP - 2 DP - 2006 Apr TI - The role of telomeres and telomerase in the pathology of human cancer and aging. PG - 103-13 AB - Cellular senescence, the state of permanent growth arrest, is the inevitable fate of replicating normal somatic cells. Postulated to underlie this finite replicative span is the physiology of telomeres, which constitute the ends of chromosomes. The repetitive sequences of these DNA-protein complexes progressively shorten with each mitosis. When the critical length is bridged, telomeres trigger DNA repair and cell cycle checkpoint mechanisms that result in chromosomal fusions, cell cycle arrest, senescence and/or apoptosis. Should senescence be bypassed at such time, continued cell divisions in the face of dysfunctional telomeres and activated DNA repair machinery can result in the genomic instability favourable for oncogenesis. The longevity and malignant progression of the thus transformed cell requires coincident telomerase expression or other means to negate the constitutional telomeric loss. Practically then, telomeres and telomerase may represent plausible prognostic and screening cancer markers. Furthermore, if the argument is extended, with assumptions that telomeric attrition is indeed the basis of cellular senescence and that accumulation of the latter equates to aging at the organismal level, then telomeres may well explain the increased incidence of cancer with human aging. AD - Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, Australia. jshi4495@usyd.edu.au FAU - Shin, Joo-Shik AU - Shin JS FAU - Hong, Angela AU - Hong A FAU - Solomon, Michael J AU - Solomon MJ FAU - Lee, C Soon AU - Lee CS LA - eng PT - Journal Article PT - Review PL - England TA - Pathology JT - Pathology JID - 0175411 RN - 0 (DNA, Neoplasm) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Aging/*physiology MH - DNA Repair/physiology MH - DNA, Neoplasm/physiology MH - Humans MH - Neoplasms/*metabolism MH - Telomerase/*physiology MH - Telomere/*physiology RF - 244 EDAT- 2006/04/04 09:00 MHDA- 2006/06/09 09:00 CRDT- 2006/04/04 09:00 AID - Q07245T610216RH8 AID - 10.1080/00313020600580468 PST - ppublish SO - Pathology. 2006 Apr;38(2):103-13. PMID- 16131355 OWN - NLM STAT- MEDLINE DA - 20050831 DCOM- 20051110 LR - 20080310 IS - 0002-8614 (Print) VI - 53 IP - 9 Suppl DP - 2005 Sep TI - Telomere biology in aging and cancer. PG - S292-4 AB - It is thought that a limited investment by the body in many types of maintenance and repair causes aging. Cell turnover is one mechanism of replacing damaged cells, and cell division thus contributes to good repair, but the number of times cells can divide is limited to form a barrier against cancer. Precancerous cells must divide many times to accumulate all of the mutations needed to become malignant. Limiting the number of times they can divide helps prevent cancer. The mechanism for counting cell divisions lies in structures at the ends of the chromosomes called telomeres that shorten with every division, eventually causing cell aging. This shortening can be prevented and cells immortalized using the enzyme telomerase, which can elongate telomeres. Immortalizing all of the cells in the body might increase repair but would remove the barrier to malignancy and would probably cause premature death from cancer in many cases, although the ability to immortalize cells opens up enormous opportunities for using normal cells for therapeutic purposes in localized areas. Eventually, once better controls and treatments for cancer are available, cellular rejuvenation by manipulating telomeres may reduce some of the physiological declines that accompany aging. Such treatments should increase health span, but because replicative aging represents only one of many processes that may contribute to overall human aging, modest increases in life span are expected at best. AD - Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Building K2.206, MC 9039, Dallas, TX 75235, USA. woodring.wright@utsouthwestern.edu FAU - Wright, Woodring E AU - Wright WE FAU - Shay, Jerry W AU - Shay JW LA - eng PT - Journal Article PL - United States TA - J Am Geriatr Soc JT - Journal of the American Geriatrics Society JID - 7503062 RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Aging/*genetics/physiology MH - Animals MH - Biology MH - Cell Aging/physiology MH - Cell Division/physiology MH - Cell Survival/physiology MH - Humans MH - Longevity/genetics MH - Neoplasms/*genetics MH - Rejuvenation/physiology MH - Telomerase/physiology MH - Telomere/genetics/*physiology EDAT- 2005/09/01 09:00 MHDA- 2005/11/11 09:00 CRDT- 2005/09/01 09:00 AID - JGS53492 AID - 10.1111/j.1532-5415.2005.53492.x PST - ppublish SO - J Am Geriatr Soc. 2005 Sep;53(9 Suppl):S292-4. PMID- 16034678 OWN - NLM STAT- MEDLINE DA - 20050721 DCOM- 20051207 LR - 20061115 IS - 1389-5729 (Print) VI - 6 IP - 2 DP - 2005 TI - Analysis of telomere length and telomerase activity in tree species of various life-spans, and with age in the bristlecone pine Pinus longaeva. PG - 101-11 AB - Normal somatic cells have a finite replicative capacity. With each cell division, telomeres (the physical ends of linear chromosomes) progressively shorten until they reach a critical length, at which point the cells enter replicative senescence. Some cells maintain telomere length by the action of the telomerase enzyme. The bristlecone pine, Pinus longaeva, is the oldest known living eukaryotic organism, with the oldest on record turning 4770 years old in 2005. To determine what changes occur, if any, in telomere length and telomerase activity with age, and what roles, if any, telomere length and telomerase activity may play in contributing to the increased life-span and longevity of P. longaeva with age, as well as in other tree species of various life-spans, we undertook a detailed investigation of telomere length and telomerase activity in such trees. The results from this study support the hypothesis that both increased telomere length and telomerase activity may directly/indirectly contribute to the increased life-span and longevity evident in long-lived pine trees (2000-5000 year life-spans) compared to medium-lived (400-500 year life-span) and short-lived (100-200 year life-span) pine trees, as well as in P. longaeva with age. AD - Department of Neuroscience, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, 32610-0244, USA. beflana@ufl.edu FAU - Flanary, Barry E AU - Flanary BE FAU - Kletetschka, Gunther AU - Kletetschka G LA - eng PT - Journal Article PL - Netherlands TA - Biogerontology JT - Biogerontology JID - 100930043 RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Aging/*physiology MH - Enzyme Activation MH - Longevity/physiology MH - Pinus/*classification/*physiology MH - Species Specificity MH - Telomerase/*physiology MH - Telomere/*physiology/*ultrastructure EDAT- 2005/07/22 09:00 MHDA- 2005/12/13 09:00 CRDT- 2005/07/22 09:00 PHST- 2004/10/21 PHST- 2005/02/01 AID - 10.1007/s10522-005-3484-4 PST - ppublish SO - Biogerontology. 2005;6(2):101-11. PMID- 15721260 OWN - NLM STAT- MEDLINE DA - 20050221 DCOM- 20050329 LR - 20090602 IS - 1097-2765 (Print) VI - 17 IP - 4 DP - 2005 Feb 18 TI - Late S phase-specific recruitment of Mre11 complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae. PG - 573-83 AB - In Saccharomyces cerevisiae, telomere replication occurs in late S phase and is accompanied by dynamic remodeling of its protein components. Here, we show that MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S phase. MRX is required for the late S phase-specific recruitment of ATR-like kinase Mec1 to the telomeres. Mec1, in turn, contributes to the assembly of the telomerase regulators Cdc13 and Est1 at the telomere ends. Our results provide a model for the hierarchical assembly of telomere-replication proteins in late S phase; this involves triggering by the loading of MRX onto the chromosome termini. The recruitment of DNA repair-related proteins to the telomeres at particular times in the cell cycle suggests that the normal terminus of a chromosome is recognized as a DSB during the course of replication. AD - Department of Geriatric Research, National Institute for Longevity Sciences, Obu, Aichi 474-8522, Japan. FAU - Takata, Hideki AU - Takata H FAU - Tanaka, Yayoi AU - Tanaka Y FAU - Matsuura, Akira AU - Matsuura A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell JT - Molecular cell JID - 9802571 RN - 0 (DNA-Binding Proteins) RN - 0 (RAD50 protein, S cerevisiae) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 0 (XRS2 protein, S cerevisiae) RN - 9007-49-2 (DNA) RN - EC 2.7.11.1 (MEC1 protein, S cerevisiae) RN - EC 3.1.- (Endodeoxyribonucleases) RN - EC 3.1.- (Exodeoxyribonucleases) RN - EC 3.1.- (MRE11 protein, S cerevisiae) SB - IM MH - Chromatin Immunoprecipitation MH - DNA/genetics MH - *DNA Repair MH - *DNA Replication MH - DNA-Binding Proteins/genetics/metabolism MH - Endodeoxyribonucleases/*genetics/metabolism MH - Exodeoxyribonucleases/*genetics/metabolism MH - Phenotype MH - *S Phase MH - Saccharomyces cerevisiae/genetics/metabolism MH - Saccharomyces cerevisiae Proteins/*genetics/metabolism MH - Telomere/*genetics/metabolism EDAT- 2005/02/22 09:00 MHDA- 2005/03/30 09:00 CRDT- 2005/02/22 09:00 PHST- 2004/10/12 PHST- 2004/12/28 PHST- 2005/01/20 AID - S1097276505010506 AID - 10.1016/j.molcel.2005.01.014 PST - ppublish SO - Mol Cell. 2005 Feb 18;17(4):573-83. PMID- 14729022 OWN - NLM STAT- MEDLINE DA - 20040119 DCOM- 20040921 LR - 20041117 IS - 0306-9877 (Print) VI - 62 IP - 1 DP - 2004 TI - Tying it all together: telomeres, sexual size dimorphism and the gender gap in life expectancy. PG - 151-4 AB - The classic explanation that women outlive men solely due to hormonal and lifestyle differences, does not withstand a critical analysis. In developed countries, the average gap in life expectancy between the sexes is 7 years. It has widened over the last decades, despite the trend of women copying the 'unhealthy' lifestyle of men. Estrogen levels in postmenopausal women are virtually identical to estrogen levels in males and can hardly explain the discrepancy. Furthermore, testosterone got its bad reputation from one study on mentally retarded men, which has to be interpreted with caution. However, sexual size dimorphism with men being the larger sex in conjunction with the limited replication potential of human somatic cells might account for higher mortality rates in males, especially at old age. The hypothesis, as presented here, is based on the well-known concept of a cellular mitotic clock, which was discovered by Leonard Hayflick almost half a century ago. The underlying counting mechanism, namely the gradual erosion of chromosome ends (telomeres) due to the end replication problem of linear DNA molecules, was first described by Alexey Olovnikov in 1971 and with minor modifications has become a widely accepted paradigm. In a recent Lancet study, an inverse correlation between mean telomere length and mortality in people has been found. In this and two other studies, it was confirmed that males do have shorter telomeres than females at the same age. This is almost certainly a consequence of men being usually taller than women, although nobody has done an investigation yet. Clearly, a larger body requires more cell doublings, especially due to the ongoing regeneration of tissues over a lifetime. Accordingly, the replicative history of male cells might be longer than that of female cells, resulting in the exhaustion of the regeneration potential and the early onset of age-associated diseases predominantly in large-bodied males. Inherited telomere length variation between unrelated individuals might have obscured a clear correlation between body height and mortality, leading to conflicting results in some studies. Finally, I propose that the secular height increase over the last decades, of about 2.5 cm per generation in the western world, has to be blamed for the widening of the gender gap in life expectancy. AD - Institut fur Medizinische Biologie, Medizinische Universitat Wien, Wahringerstrasse 10, 1090 Vienna, Austria. reinhard_stindl@yahoo.de FAU - Stindl, Reinhard AU - Stindl R LA - eng PT - Journal Article PL - Scotland TA - Med Hypotheses JT - Medical hypotheses JID - 7505668 SB - IM MH - Aging/physiology MH - Body Constitution/*physiology MH - Cell Aging/physiology MH - Female MH - Humans MH - Life Expectancy/*trends MH - Longevity/*physiology MH - Male MH - *Models, Biological MH - Mortality/*trends MH - Risk Factors MH - Sex Distribution MH - Sex Factors MH - Survival Analysis MH - Telomere/chemistry/*physiology/ultrastructure EDAT- 2004/01/20 05:00 MHDA- 2004/09/24 05:00 CRDT- 2004/01/20 05:00 AID - S0306987703003165 PST - ppublish SO - Med Hypotheses. 2004;62(1):151-4. PMID- 14577056 OWN - NLM STAT- MEDLINE DA - 20031024 DCOM- 20031208 LR - 20051116 IS - 0026-0495 (Print) VI - 52 IP - 10 Suppl 2 DP - 2003 Oct TI - Genes of aging. PG - 5-9 AB - According to developmental genetics theories, aging is a genetically programmed and controlled continuum of development and maturation. Being dynamic and malleable processes, development and aging are controlled not only by genes but also by environmental and epigenetic influences that predominate in the second half of life. Genetic mutations affect many phenotypes in flies, worms, rodents, and humans which share several diseases or their equivalents, including cancer, neurodegeneration, and infectious disorders as well as their susceptibility to them. Life span and stress resistance are closely linked. Oxidative stress actually constitutes a defined hypothesis of aging in that macromolecule oxidative damage accumulates with age and tends to be associated with life expectancy. DNA methylation, a force in the regulation of gene expression, is also one of the biomarkers of genetic damage. The mitotic clock of aging is marked, if not guided, by telomeres, essential genetic elements stabilizing natural chromosomic ends. The dream of humans to live longer, healthy lives is being tested by attempts to modify longevity in animal models, frequently by dietary manipulation. The quest continues to understand the mechanisms of healthy aging, one of the most compelling areas of research in the 21st century. AD - Centre de recherche, CHUM-Hotel-Dieu, Universite Montreal, Montreal, Quebec, Canada. FAU - Hamet, Pavel AU - Hamet P FAU - Tremblay, Johanne AU - Tremblay J LA - eng PT - Journal Article PT - Review PL - United States TA - Metabolism JT - Metabolism: clinical and experimental JID - 0375267 SB - IM MH - Aging/*genetics MH - Animals MH - DNA Methylation MH - Humans MH - Longevity/genetics MH - Mutation MH - Oxidative Stress MH - Telomere RF - 66 EDAT- 2003/10/25 05:00 MHDA- 2003/12/10 05:00 CRDT- 2003/10/25 05:00 AID - S0026049503002944 PST - ppublish SO - Metabolism. 2003 Oct;52(10 Suppl 2):5-9. PMID- 12965030 OWN - NLM STAT- MEDLINE DA - 20030910 DCOM- 20031007 LR - 20081120 IS - 0962-8452 (Print) VI - 270 IP - 1522 DP - 2003 Jul 7 TI - Telomeres shorten more slowly in long-lived birds and mammals than in short-lived ones. PG - 1387-92 AB - We know very little about physiological constraints on the evolution of life-history traits in general, and, in particular, about physiological and molecular adjustments that accompany the evolution of variation in lifespan. Identifying mechanisms that underlie adaptive variation in lifespan should provide insight into the evolution of trade-offs between lifespan and other life-history traits. Telomeres, the DNA caps at the ends of linear chromosomes, usually shorten as animals age, but whether telomere rate of change is associated with lifespan is unknown. We measured telomere length in erythrocytes from five bird species with markedly different lifespans. Species with shorter lifespans lost more telomeric repeats with age than species with longer lifespans. A similar correlation is seen in mammals. Furthermore, telomeres did not shorten with age in Leach's storm-petrels, an extremely long-lived bird, but actually lengthened. This novel finding suggests that regulation of telomere length is associated not only with cellular replicative lifespan, but also with organismal lifespan, and that very long-lived organisms have escaped entirely any telomeric constraint on cellular replicative lifespan. AD - Department of Zoology and Genetics, Iowa State University, Ames, IA 50011, USA. hauss@iastate.edu FAU - Haussmann, Mark F AU - Haussmann MF FAU - Winkler, David W AU - Winkler DW FAU - O'Reilly, Kathleen M AU - O'Reilly KM FAU - Huntington, Charles E AU - Huntington CE FAU - Nisbet, Ian C T AU - Nisbet IC FAU - Vleck, Carol M AU - Vleck CM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - England TA - Proc Biol Sci JT - Proceedings. Biological sciences / The Royal Society JID - 101245157 SB - IM MH - Aging/genetics/physiology MH - Animals MH - Birds/*genetics/*physiology MH - Erythrocytes/cytology/metabolism MH - Longevity/*genetics/*physiology MH - Mammals/genetics/*physiology MH - Species Specificity MH - Telomere/genetics/*physiology PMC - PMC1691385 OID - NLM: PMC1691385 EDAT- 2003/09/11 05:00 MHDA- 2003/10/08 05:00 CRDT- 2003/09/11 05:00 AID - 10.1098/rspb.2003.2385 PST - ppublish SO - Proc Biol Sci. 2003 Jul 7;270(1522):1387-92. PMID- 12890857 OWN - NLM STAT- MEDLINE DA - 20030731 DCOM- 20031008 LR - 20041117 IS - 1539-6150 (Electronic) VI - 2003 IP - 30 DP - 2003 Jul 30 TI - Mouse and human cells versus oxygen. PG - PE21 AB - Mice and humans are at opposite ends of the mammalian spectrum of longevity. A major question in biology is whether this difference can be accounted for by differences in the properties of cells from these two species. A new publication from Judith Campisi's lab reports that human cells in culture are more resistant than mouse cells to the damaging effects of 20% oxygen. The greater burden of DNA damage sustained by mouse cells causes them to rapidly enter a phase of culture in which most cells enter permanent growth arrest (replicative senescence). However, some mouse cells usually escape from senescence and then grow into an immortal cell line. This never happens in human fibroblast cell cultures. Human cells also eventually enter replicative senescence in culture, but this phenomenon is caused by shortening of telomeres and not by DNA damage of the type responsible for mouse cell senescence. Human fibroblasts never spontaneously escape from senescence. This Perspective reviews differences between mouse and human cells that could account for these differences in behavior. Some evidence indicates that human cells are generally more resistant than mouse cells to oxidative damage to DNA, but more needs to be done to confirm this finding and to understand the underlying mechanisms. Whether or not there are differences in the amount of DNA damage caused by oxygen or in the early phase of repair, there may be important differences in the later consequences of DNA damage. Mouse cells appear to be able to continue to divide with DNA damage that has not been repaired or has been misrepaired, and becomes fixed in the form of chromosomal abnormalities. The checkpoints that cause cells to stop dividing when chromosomes develop abnormalities (aberrations or shortened telomeres) appear to operate more efficiently in human cells. Much more work is needed to understand the basis for these differences and the implications for aging and cancer. AD - Sam and Ann Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, USA. hornsby@uthscsa.edu FAU - Hornsby, Peter J AU - Hornsby PJ LA - eng PT - Journal Article DEP - 20030730 PL - United States TA - Sci Aging Knowledge Environ JT - Science of aging knowledge environment : SAGE KE JID - 101146039 RN - 0 (Reactive Oxygen Species) RN - 7782-44-7 (Oxygen) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Cell Aging/*physiology MH - Cells, Cultured MH - Chromosome Aberrations MH - DNA/metabolism MH - DNA Repair MH - Humans MH - Mice MH - Neoplasms/pathology MH - Oxidative Stress/physiology MH - Oxygen/*physiology MH - Reactive Oxygen Species/*metabolism MH - Species Specificity EDAT- 2003/08/02 05:00 MHDA- 2003/10/09 05:00 CRDT- 2003/08/02 05:00 AID - 2003/30/pe21 PST - epublish SO - Sci Aging Knowledge Environ. 2003 Jul 30;2003(30):PE21. PMID- 12596689 OWN - NLM STAT- MEDLINE DA - 20030217 DCOM- 20030319 LR - 20061115 IS - 0398-0499 (Print) VI - 27 Spec No DP - 2002 Jul TI - PG - S19-23 AB - Major developments in molecular biology in invertebrates have recently shown the determining effect of genetics on aging. The first finding was that artificial selection can highlight the genetic aspect of the aging process, demonstrating the polygenetic property of longevity. Another finding showed that certain gene transfers can modulate the lifespan of an organism. Recent progress has been made in three fields: genetic markers of aging, biological basis of cell maintenance, and hereditary factors contributing to late onset genetic disease. These new developments open new avenues of research in clinical biology. In regard to genetic markers of aging, it has been demonstrated that the ends of the chromosomes, telomeres, play a role in cell senescence. Telomeres can be viewed as markers of aging. Shortened telomeres are associated with replicative senescence and antitumor action. DNA anomalies are also more frequent: simple or double breaks, additions and base substitutions. Data on the biological basis of cell maintenance obtained in invertebrates show the polygenetic property of aging involving four significant mechanisms, control of metabolism, resistance to stress, chromatin-dependent gene regulation of genetic homeostasis. Finally, recent studies have shown that late onset hereditary diseases would be linked with particular genes, some of which have been identified. Two non-exclusive mechanisms could be involved: an adaptive mechanism involving gene selection during the evolutionary process, for example in obesity; and non-adaptive accumulation of gene expression during the post-reproductive phase, for example in Alzheimer's disease. These findings open a new era for the biology of aging. AD - Centre de Recherches Gerontologiques de l'Association Claude Bernard, INSERM U 450, Developpement, Vieillissement et pathologie de la retine, Institut de Recherche Biomedicale des Cordeliers, Batiment B, Paris. treton@infobiogen.fr FAU - Treton, J AU - Treton J LA - fre PT - English Abstract PT - Journal Article PT - Review TT - Aspects fondamentaux du grand vieillissement. PL - France TA - J Mal Vasc JT - Journal des maladies vasculaires JID - 7707965 RN - 0 (DNA, Mitochondrial) RN - 0 (DNA, Ribosomal) RN - 0 (Free Radicals) RN - 0 (Reactive Oxygen Species) SB - IM MH - Aged MH - Aging/genetics/*physiology MH - Animals MH - Cell Death MH - DNA Damage MH - DNA, Mitochondrial/genetics MH - DNA, Ribosomal/genetics MH - Environment MH - Female MH - Free Radicals/adverse effects MH - Homeostasis MH - Humans MH - Invertebrates/genetics/physiology MH - Male MH - Mice MH - Oxidative Stress MH - Polymorphism, Genetic MH - Reactive Oxygen Species/adverse effects MH - Saccharomyces cerevisiae/genetics MH - Telomere/physiology MH - Werner Syndrome/genetics RF - 19 EDAT- 2003/02/25 04:00 MHDA- 2003/03/20 04:00 CRDT- 2003/02/25 04:00 PST - ppublish SO - J Mal Vasc. 2002 Jul;27 Spec No:S19-23. PMID- 12393949 OWN - NLM STAT- MEDLINE DA - 20021023 DCOM- 20030221 LR - 20061115 IS - 0304-324X (Print) VI - 48 IP - 6 DP - 2002 Nov-Dec TI - Aging Liver. A review. PG - 343-53 AB - Aging is characterized by a progressive decline of cellular functions. The aging liver appears to preserve its function relatively well. Aging is associated in human liver with morphological changes such as decrease in size attributable to decreased hepatic blood flow. Ultrastructural analysis of the human liver has revealed that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. Reactive oxygen species (ROS) are involved in the aging process and result mainly from nonenzymatic processes in the liver. Endogenous free radicals are generated within mitochondria and suspected to cause severe injury to mitochondrial DNA. This damaged DNA accumulates with aging. In addition, polyunsaturated fatty acids, highly sensitive to ROS, decrease in liver mitochondria from human centenarians, a feature acquired during evolution as a protective mechanism to favor longevity. Diet is considered the main environmental factor having effect on lifespan. It has a major impact on aging liver, the central metabolic organ of the body. The ubiquitin proteolytic pathway in the liver serves to destroy many proteins, among them p21 which is encoded by abundant mRNA in senescent cells, can inhibit cell proliferation and favors DNA repair. Drug therapy in the elderly may be complicated by several factors such as decline in body weight, renal function, liver mass and hepatic blood flow, making adverse drug reactions more frequent. Hepatic drug metabolism is mainly mediated by the cytochrome P(450 )system and drug interactions in the elderly are likely related to the progressive decline of this system after the fifth decade of life and another decrease in individuals aged 70. Antihypertensive therapy in the elderly depends upon either hepatic or renal function and should be adjusted accordingly. Finally, telomerases are the biological clocks of replicative lifespan. Shortening of telomeric ends of chromosomes correlates with aging and decline in the replicative potential of the cell: replicative senescence. Telomere DNA of human somatic cells shortens during each cell division thus leading to a finite proliferation. Transfection of the telomerase reverse transcriptase gene results in elongation of telomeres and extension of lifespan. This also applies to humans. Replicative senescence in human cells evolved as a mechanism to protect them from continuous divisions leading to multiple mutations. Longer-lived species such as humans had to develop replicative senescence to ensure that they would have the increased protection that their longevity necessitates. CI - Copyright 2002 S. Karger AG, Basel AD - Department of Medicine, FUHS/Chicago Medical School and Veterans Affairs Medical Center, North Chicago, IL 60064, USA. FAU - Anantharaju, Abhinandana AU - Anantharaju A FAU - Feller, Axel AU - Feller A FAU - Chedid, Antonio AU - Chedid A LA - eng PT - Journal Article PT - Review PL - Switzerland TA - Gerontology JT - Gerontology JID - 7601655 RN - 0 (Free Radicals) RN - 0 (Pharmaceutical Preparations) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Aging/*physiology MH - Diet MH - Free Radicals/metabolism MH - Humans MH - Liver/drug effects/pathology/*physiology MH - Pharmaceutical Preparations/administration dosage MH - Telomerase/metabolism RF - 95 EDAT- 2002/10/24 04:00 MHDA- 2003/02/22 04:00 CRDT- 2002/10/24 04:00 AID - ger48343 PST - ppublish SO - Gerontology. 2002 Nov-Dec;48(6):343-53. PMID- 11029502 OWN - NLM STAT- MEDLINE DA - 20001205 DCOM- 20001205 LR - 20071115 IS - 1019-6439 (Print) VI - 17 IP - 5 DP - 2000 Nov TI - Telomere length maintenance in aging and carcinogenesis. PG - 981-9 AB - Normal somatic cells have a finite number of divisions, a limited capacity to proliferate. Human telomeres, the long DNA TTAGGG repeats at the ends of chromosomes, are considered a molecular clock marker. The gradual and progressive telomere shortening at each replicative cycle is associated, through the activation of pRB and p53 pathways and genomic instability, to the replicative senescence, a non-dividing state and widespread cell death. Activation of telomere maintenance can revert this program. Although not completely known, several mechanisms and modulating agents may be able to up and down-regulate telomere length and its maintenance. Chemopreventive therapies for the up-regulation of telomerase activity, able to prolong the life of cell cultures in a phenotypically youthful state, could have important applications in research and medicine. On the contrary the therapeutic down-regulation of telomerase activity may be used in cancer therapy. Telomerase expression per se is not oncogenic, but telomere shortening and maintenance seem to be crucial events in tumor formation. Thus a particular focus has been pointed out relatively to the immortalization of normal or potential pre-cancerous cells. With the extension of life span the probability to get in contact with carcinogens increases, genetic instability, oncogene activation and/or onco-suppressor gene inactivation (i.e. p53, pRB, ras): the cancer transformation can be then induced in predisposed cells, depending on their genetic context, by the activation of telomere maintenance. Pharmacological intervention may be able to modulate the rate of living, by increasing life span of few specific target cells, or decreasing it in proliferating cancer and pre-cancer cells. Because of the unknown state of the enormous cell number of the human organism, is it safe to extend the human life span by therapeutic agents? AD - Unita Operativa di Oncologia Medica, Universita di Messina, Messina, Italy. aragona@sirio-oncology.it FAU - Aragona, M AU - Aragona M FAU - Maisano, R AU - Maisano R FAU - Panetta, S AU - Panetta S FAU - Giudice, A AU - Giudice A FAU - Morelli, M AU - Morelli M FAU - La Torre, I AU - La Torre I FAU - La Torre, F AU - La Torre F LA - eng PT - Journal Article PT - Review PL - GREECE TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (Ankyrins) RN - 0 (Antineoplastic Agents) RN - 0 (Antioxidants) RN - 0 (Carrier Proteins) RN - 0 (DNA, Neoplasm) RN - 0 (DNA-Binding Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Free Radicals) RN - 0 (Neoplasm Proteins) RN - 0 (RNA, Untranslated) RN - 0 (TEP1 protein, human) RN - 0 (Telomeric Repeat Binding Protein 2) RN - 0 (hTR RNA) RN - 0 (telomerase RNA) RN - 63231-63-0 (RNA) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) RN - EC 2.7.7.49 (Telomerase) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) SB - IM MH - Aging/*genetics/pathology MH - Ankyrins/physiology MH - Antineoplastic Agents/pharmacology MH - Antioxidants/pharmacology MH - Carrier Proteins/physiology MH - Cell Aging/*genetics/physiology MH - Cell Division/genetics/physiology MH - Cell Transformation, Neoplastic/genetics MH - Chromosomes, Human/ultrastructure MH - DNA Replication MH - DNA, Neoplasm/genetics MH - DNA-Binding Proteins/physiology MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Free Radicals MH - Homeostasis MH - Humans MH - Longevity/genetics MH - MAP Kinase Signaling System MH - Neoplasm Proteins/antagonists inhibitors/physiology MH - Neoplasms/*genetics/ultrastructure MH - Oxidative Stress MH - Phosphoprotein Phosphatases/antagonists inhibitors/physiology MH - Poly(ADP-ribose) Polymerases/physiology MH - *RNA MH - RNA, Untranslated/physiology MH - Tandem Repeat Sequences MH - Telomerase/antagonists inhibitors/physiology MH - Telomere/*ultrastructure MH - Telomeric Repeat Binding Protein 2 MH - Transfection RF - 96 EDAT- 2000/10/13 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/13 11:00 PST - ppublish SO - Int J Oncol. 2000 Nov;17(5):981-9. PMID- 8593161 OWN - NLM STAT- MEDLINE DA - 19960401 DCOM- 19960401 LR - 20061115 IS - 0265-9247 (Print) VI - 18 IP - 1 DP - 1996 Jan TI - Endless quest. PG - 3-5 AB - The replication of linear chromosome DNA by DNA polymerase leads to the loss of terminal sequences, in the absence of a special mechanism to maintain ends or telomeres. This mechanism is known to consist of short terminal repeats and the enzyme telomerase, which contains RNA complementary to the DNA repeats. There is evidence that telomeric DNA continually decreases in size in the absence of telomerase, and this is followed by cellular senescence. Immortalisation of somatic cells is accompanied, at least in some cases, by acquisition of telomerase activity. The cloning of DNA coding for the RNA component of telomerase has opened up some new experimental approaches, including the study of telomerases with mutant RNA. The telomere theory of cellular senescence appears to provide a molecular basis for the 'Hayflick limit' to human fibroblast growth. However the telomeres and behaviour of primary mouse cells are anomolous, and many immortalised human cell lines lack normal telomerase activity. These exceptions are not easily accommodated in the telomere theory. AD - CSIRO Division of Biomolecular Engineering, North Ryde, NSW, Sydney, Australia. FAU - Holliday, R AU - Holliday R LA - eng PT - Journal Article PT - Review PL - ENGLAND TA - Bioessays JT - BioEssays : news and reviews in molecular, cellular and developmental biology JID - 8510851 RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Animals MH - Base Sequence MH - Cell Aging/*physiology MH - Cell Division/physiology MH - Cell Line, Transformed MH - Cell Transformation, Neoplastic MH - DNA Replication/*physiology MH - Humans MH - Longevity MH - Mice MH - Molecular Sequence Data MH - Muridae/physiology MH - Repetitive Sequences, Nucleic Acid MH - Species Specificity MH - Telomerase/*physiology MH - *Telomere/physiology RF - 26 EDAT- 1996/01/01 MHDA- 1996/01/01 00:01 CRDT- 1996/01/01 00:00 AID - 10.1002/bies.950180103 PST - ppublish SO - Bioessays. 1996 Jan;18(1):3-5.
http://www.sciencenet.cn/htmlnews/2009/11/225093.shtm 北京大学田小利小组发现两个与长寿相关基因 北京大学分子医学研究所人类群体遗传研究室田小利教授与国家发展研究院中国经济研究中心曾毅教授联合研究组发现FOXO1A和FOXO3A基因与长寿相关。他们的研究表明FOXO1A与我国女性的长寿相关，而FOXO3A基因则没有性别差异。该研究结果发表于经典遗传学杂志《人类分子遗传学》（ Human Molecular Genetics ）。 健康长寿是每一个人的梦想，但影响健康长寿的因素很多，包括性别、遗传、生活习惯和生活环境及其相互作用等。在年龄大于85岁的人群中女性约占70-85%，而男性仅为15-30%。尽管女性的长寿优势可见于已经报道的所有人种，但原因尚不明确。田小利教授研究组首次发现FOXO1A基因与女性的长寿相关，将有助于解释女性长寿之谜。FOXO3A基因曾报道与其他的人群（如日本人、德国人和意大利人等）的长寿相关。中国人FOXO3A基因的长寿位点与其他人群的长寿位点共存于一个单倍型中。 FOXO1A和FOXO3A是胰岛素或胰岛素样生长因子介导的下游信号通路分子，与细胞周期、生长、凋亡以及血管新生等有密切关系。在代谢方面，它们的主要功能是平衡胰岛素的敏感性和抗性，参与癌症、自身免疫病以及心血管疾病如缺血性心脏病、心肌肥大等。田小利教授等推测FOXO3A可能通过调节胰岛素抗性和长寿相关，而FOXO1A则除调节胰岛素抗性外，可能还通过与女性生殖系统相互作用而影响人的寿命。 田小利教授研究组主要致力于寻找心血管疾病相关基因，并研究它们在心血管系统的发育、疾病及衰老过程中的作用机制。比较分析患病与健康人群和长寿与普通人群的遗传位点的异同，寻找心血管疾病致病和保护基因是重要的研究手段。在这个研究中，他们比较分析了1000个百岁老人和1000个年轻人的FOXO1A及FOXO3A基因型，得出这两个基因与长寿相关的结论。其中1000个百岁老人基因来自曾毅教授课题组1998年收集的4000份高龄老人血样。参与此研究的还有重庆第三军医大学祝之明教授、华西医科大学莫显明教授以及宁波市第一医院陈晓敏教授等。 目前北京大学健康长寿跨学科研究团队正在研究社会、行为、环境与FOXO1A及FOXO3A基因的相互作用，期望发现遗传、社会、行为、环境因素等相互作用影响老年人的健康与长寿的可能机制。 更多阅读 《人类分子遗传学》发表论文摘要（英文） http://hmg.oxfordjournals.org/cgi/content/abstract/ddp459v1?maxtoshow=HITS=10hits=10RESULTFORMAT=fulltext=yi+zengsearchid=1FIRSTINDEX=0resourcetype=HWCIT Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations Yang Li 1 , , Wen-Jing Wang 1 , , Huiqing Cao 1 , , Jiehua Lu 8 , Chong Wu 1 , Fang-Yuan Hu 1 , Jian Guo 1 , Ling Zhao 1 , Fan Yang 1 , Yi -Xin Zhang 1 , Wei Li 1 , Gu-Yan Zheng 1 , Hanbin Cui 4 , Xiaomin Chen 5 , Zhiming Zhu 6 , Hongbo He 6 , Birong Dong 7 , Xianming Mo 7 , Yi Zeng 2 ,3 ,* and Xiao-Li Tian 1 ,* 1 Department of Human Population Genetics, Institute of Molecular Medicine and 2 China Center for Economic Research, National School of Development, Peking University, 5 Yi heyuan Rd., Beijing 100871, China 3 Center for Study of Aging and Human Development, Medical School of Duke University, BUSSE Building, Duke University, Durham, NC 27710, USA, 4 Key Laboratory of Ningbo First Hospital and 5 Cardiovascular Center of Ningbo First Hospital, Ningbo University, Liuting Str. 59 Ningbo 315010, 6 Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, and 7 Department of Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China 8 Department of Sociology and Center for Healthy Aging and Family Studies, Peking University * To whom correspondence should be addressed at: Department of Human Population Genetics, 316N Yi ngjie Conference Center, Peking University, 5 Yi heyuan Rd., Beijing 100871, China, Tel: +86 1062755397; Fax: +86 1062756926; Email: tianxiaoli@pku.edu.cn
标签: 长寿
