Telomeres and Aging

[Michael Scally MD]

A key feature to men’s health is to live a long and full life. The following is an interesting twist on the longevity issue. The hypothesis is that telomere length affects the rate of physical decline both internally and externally. Can we really do much to change this? There is a body of research striving to do just that!

Study: Looking young may mean living longer

Dec 14, 2009

LONDON – Those baby-faced people now have another reason to be smug: a new Danish study says looking young apparently means a longer life. Research published online Monday in the British Medical Journal suggests that people who look younger than their years also live longer.

In 2001, Danish researchers conducted physical and cognitive tests on more than 1,800 pairs of twins over aged 70, as well as taking photos of their faces. Three groups of people who didn't know the twins' real ages guessed how old they were. The researchers then tracked how long the twins survived over 7 years.

The experts found that people who looked younger than their actual age were far more likely to survive, even after they adjusted for other factors like gender and environment. The bigger the difference in perceived age within any twin pair, the more likely it was that the older-looking twin died first.

They also found a possible biological explanation: people who looked younger also tended to have longer telomeres, a key DNA component that is linked to aging. People with shorter telomeres are thought to age faster. In the Danish study, the more fresh-faced people had longer telomeres.

The authors said that perceived age, which is widely used by doctors as a general indicator of a patient's health, is a good biomarker of aging that predicts survival among people over age 70.

http://news.yahoo.com/s/ap/20091214/ap_on_sc/eu_looking_young


Christensen K, Thinggaard M, McGue M, et al. Perceived age as clinically useful biomarker of ageing: cohort study. BMJ 2009;339(dec11_2):b5262-.

Objective To determine whether perceived age correlates with survival and important age related phenotypes. Design Follow-up study, with survival of twins determined up to January 2008, by which time 675 (37%) had died. Setting Population based twin cohort in Denmark. Participants 20 nurses, 10 young men, and 11 older women (assessors); 1826 twins aged [≥]70. Main outcome measures Assessors: perceived age of twins from photographs. Twins: physical and cognitive tests and molecular biomarker of ageing (leucocyte telomere length). Results For all three groups of assessors, perceived age was significantly associated with survival, even after adjustment for chronological age, sex, and rearing environment. Perceived age was still significantly associated with survival after further adjustment for physical and cognitive functioning. The likelihood that the older looking twin of the pair died first increased with increasing discordance in perceived age within the twin pair--that is, the bigger the difference in perceived age within the pair, the more likely that the older looking twin died first. Twin analyses suggested that common genetic factors influence both perceived age and survival. Perceived age, controlled for chronological age and sex, also correlated significantly with physical and cognitive functioning as well as with leucocyte telomere length. Conclusion Perceived age--which is widely used by clinicians as a general indication of a patient's health--is a robust biomarker of ageing that predicts survival among those aged [≥]70 and correlates with important functional and molecular ageing phenotypes.

http://www.bmj.com/cgi/content/full/339/dec11_2/b5262

 

[zkt]

Re: Study: Looking young may mean living longer

This is a good time to put in a plug for The Research Channel. I watched a very interesting lecture concerning genetics, longevity and telomeres a few weeks ago on The Research Channel via Dish Network.
You can d/l the mpeg-4 a/v or mp3 audio files here:

ResearchChannel - Stem Cells and the End of Aging

There is wealth of solid science available on this site for those who REALLY want to know.

 

[zkt]

Re: Study: Looking young may mean living longer

Here is the lecture on telomeres:
ResearchChannel - Life at the Ends of Your Chromosomes: How to Stay Forever Young?

 

[cvictorg]

Harvard scientists reverse the ageing process in mice – now for humans

Harvard scientists reverse the ageing process in mice – now for humans | Science | The Guardian

Access : Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice : Nature

Harvard scientists were surprised that they saw a dramatic reversal, not just a slowing down, of the ageing in mice. Now they believe they might be able to regenerate human organs

The Harvard group focused on a process called telomere shortening. Most cells in the body contain 23 pairs of chromosomes, which carry our DNA. At the ends of each chromosome is a protective cap called a telomere. Each time a cell divides, the telomeres are snipped shorter, until eventually they stop working and the cell dies or goes into a suspended state called "senescence". The process is behind much of the wear and tear associated with ageing.

At Harvard, they bred genetically manipulated mice that lacked an enzyme called telomerase that stops telomeres getting shorter. Without the enzyme, the mice aged prematurely and suffered ailments, including a poor sense of smell, smaller brain size, infertility and damaged intestines and spleens. But when DePinho gave the mice injections to reactivate the enzyme, it repaired the damaged tissues and reversed the signs of ageing.

"These were severely aged animals, but after a month of treatment they showed a substantial restoration, including the growth of new neurons in their brains," said DePinho.

Repeating the trick in humans will be more difficult. Mice make telomerase throughout their lives, but the enzyme is switched off in adult humans, an evolutionary compromise that stops cells growing out of control and turning into cancer. Raising levels of telomerase in people might slow the ageing process, but it makes the risk of cancer soar.

DePinho said the treatment might be safe in humans if it were given periodically and only to younger people who do not have tiny clumps of cancer cells already living, unnoticed, in their bodies

Lynne Cox, a biochemist at Oxford University, said the study was "extremely important" and "provides proof of principle that short-term treatment to restore telomerase in adults already showing age-related tissue degeneration can rejuvenate aged tissues and restore physiological function."

DePinho said none of Harvard's mice developed cancer after the treatment. The team is now investigating whether it extends the lifespan of mice or enables them to live healthier lives into old age.

 

[cvictorg]

Telomerase reactivation reverses tissue degeneration in aged telomerasedeficient mice

Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice

Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice — PNAS

Both deficiency and excess of growth hormone (GH) are associated with increased mortality and morbidity. GH replacement in otherwise healthy subjects leads to complications, whereas individuals with isolated GH deficiency such as Laron dwarfs show increased life span. Here, we determined the effects of treatment with the GH-releasing hormone (GHRH) receptor antagonist MZ-5-156 on aging in SAMP8 mice, a strain that develops with aging cognitive deficits and has a shortened life expectancy. Starting at age 10 mo, mice received daily s.c. injections of 10 ?g/mouse of MZ-5-156. Mice treated for 4 mo with MZ-5-156 showed increased telomerase activity, improvement in some measures of oxidative stress in brain, and improved pole balance, but no change in muscle strength. MZ-5-156 improved cognition after 2 mo and 4 mo, but not after 7 mo of treatment (ages 12, 14 mo, and 17 mo, respectively). Mean life expectancy increased by 8 wk with no increase in maximal life span, and tumor incidence decreased from 10 to 1.7%. These results show that treatment with a GHRH antagonist has positive effects on some aspects of aging, including an increase in telomerase activity.

So - maybe we don't need hgh after all

 

[Excallibro]

Re: Harvard scientists reverse the ageing process in mice – now for humans

This is some of the most interesting work I've seen lately. You should see the mice they genetically altered. It's breathtaking.

I suspect that there are ways around the potential cancer risks. After all, this risk increases in humans with age, anyway.

I'd be willing to be a guinea pig for this work, assuming I understood the specific mechanisms and risks beforehand.

 

[ergomaniac]

Re: Harvard scientists reverse the ageing process in mice – now for humans

yes. very much subcribed. ive read of diety factors than can alter shortening.
ive also read of differing lengths in naturally dead people or cells so theres probablly other factors. aside from gettin hit by a truck. but yes,very exiting.

 

[Michael Scally MD]

Re: Telomerase reactivation reverses tissue degeneration in aged telomerasedeficient

Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice

Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice — PNAS

Both deficiency and excess of growth hormone (GH) are associated with increased mortality and morbidity. GH replacement in otherwise healthy subjects leads to complications, whereas individuals with isolated GH deficiency such as Laron dwarfs show increased life span. Here, we determined the effects of treatment with the GH-releasing hormone (GHRH) receptor antagonist MZ-5-156 on aging in SAMP8 mice, a strain that develops with aging cognitive deficits and has a shortened life expectancy. Starting at age 10 mo, mice received daily s.c. injections of 10 ?g/mouse of MZ-5-156. Mice treated for 4 mo with MZ-5-156 showed increased telomerase activity, improvement in some measures of oxidative stress in brain, and improved pole balance, but no change in muscle strength. MZ-5-156 improved cognition after 2 mo and 4 mo, but not after 7 mo of treatment (ages 12, 14 mo, and 17 mo, respectively). Mean life expectancy increased by 8 wk with no increase in maximal life span, and tumor incidence decreased from 10 to 1.7%. These results show that treatment with a GHRH antagonist has positive effects on some aspects of aging, including an increase in telomerase activity.

So - maybe we don't need hgh after all

See attached: Banks WA, Morley JE, Farr SA, et al. Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice. Proceedings of the National Academy of Sciences 2010;107(51):22272-7.

 

[cvictorg]

Re: Telomerase reactivation reverses tissue degeneration in aged telomerasedeficient

See attached: Banks WA, Morley JE, Farr SA, et al. Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice. Proceedings of the National Academy of Sciences 2010;107(51):22272-7.

Your thoughts Dr Scally - does this offer proof that we DO NOT NEED hgh supplementation?

 

[Excallibro]

Re: Harvard scientists reverse the ageing process in mice – now for humans

yes. very much subcribed. ive read of diety factors than can alter shortening.
ive also read of differing lengths in naturally dead people or cells so theres probablly other factors. aside from gettin hit by a truck. but yes,very exiting.

There's no question that starvation lengthens lifespan, and doesn't that make sense from a genetic standpoint? If a species is on the edge, it will require longer lifespans to keep it alive, and nature tries her best to keep a balance, if not increase the number of viable species out there.

This is what's so exciting about Resveratrol and related compounds. They trick the body into thinking it's starving, which makes me wonder greatly, what effect if any, these starvation mimicking compounds are having on the telomeres, in addition to other receptors being tripped. I wonder if anyone has studied telomeres and resveratrol yet?

 

[Michael Scally MD]

Re: Harvard scientists reverse the ageing process in mice – now for humans

I will never think of DNA the same again! LMAO
[ame=http://www.colbertnation.com/the-colbert-report-videos/370184/january-06-2011/ronald-depinho]Ronald DePinho - The Colbert Report - 1/6/11 - Video Clip | Comedy Central[/ame]

 

[cvictorg]

Re: Telomerase reactivation reverses tissue degeneration in aged telomerasedeficient

See attached: Banks WA, Morley JE, Farr SA, et al. Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice. Proceedings of the National Academy of Sciences 2010;107(51):22272-7.

So Dr Scally - I ask one more time - do you think we need HGH supplementation or not??

 

[Michael Scally MD]

Re: Harvard scientists reverse the ageing process in mice – now for humans

[The following is an ongoing concern. IMO, the use of hGH should be restricted to those shown to be deficient by challenge testing. Any other use should be within a research environment.]

Clayton PE, Banerjee I, Murray PG, Renehan AG. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol 2011;7(1):11-24. Growth hormone, the insulin-like growth factor axi... [Nat Rev Endocrinol. 2011] - PubMed result

Growth hormone (GH), insulin-like growth factor (IGF)-I and insulin have potent growth-promoting and anabolic actions. Their potential involvement in tumor promotion and progression has been of concern for several decades. The evidence that GH, IGF-I and insulin can promote and contribute to cancer progression comes from various sources, including transgenic and knockout mouse models and animal and human cell lines derived from cancers. Assessments of the GH-IGF axis in healthy individuals followed up to assess cancer incidence provide direct evidence of this risk; raised IGF-I levels in blood are associated with a slightly increased risk of some cancers. Studies of human diseases characterized by excess growth factor secretion or treated with growth factors have produced reassuring data, with no notable increases in de novo cancers in children treated with GH. Although follow-up for the vast majority of these children does not yet extend beyond young adulthood, a slight increase in cancers in those with long-standing excess GH secretion (as seen in patients with acromegaly) and no overall increase in cancer with insulin treatment, have been observed. Nevertheless, long-term surveillance for cancer incidence in all populations exposed to increased levels of GH is vitally important.

 

[truthseeker]

Re: Harvard scientists reverse the ageing process in mice – now for humans

I'm a little confused here,is it stating that otherwise healthy but aged ppl are doing more harm than good using hgh,and/ or is it stating that HGRH is a safer and actually better choice because of effects on telomerase activity.Lastly the HGHR antagonist used in the study was different than what we might find at the peptide research sites ....right?

 

[Michael Scally MD]

Re: OnLine First

Telomere Dysfunction Induces Metabolic And Mitochondrial Compromise

Multiple biological processes driven by diverse molecular factors conspire progressively to diminish organ function with advancing age. Molecular and cellular analyses of age-related conditions such as muscle atrophy, diabetes and cardiomyopathy implicate diminished mitochondrial function and telomere dysfunction in driving pathogenesis. Aged tissues show accumulation of mitochondrial DNA (mtDNA) mutations causing respiratory chain deficiency and increased reactive oxygen species (ROS), which may underlie declining mitochondrial energy production and progressive loss of vigour in the aged. The importance of mitochondrial integrity for healthy ageing is reinforced by premature ageing in mitochondrial polymerase (PolgA) mutant mice, which sustain increased mtDNA mutations. Whereas the instigating processes driving age-associated mitochondrial decline are not known, in the context of this study, it is notable that the activity of the master mitochondrial regulators PGC-1a and PGC-1b decreases across ageing tissues. The relevance of PGCs to age-related pathologies may stem from their regulation of mitochondrial biogenesis and control of metabolic processes (gluconeogenesis, fatty acid metabolism and b-oxidation), processes that relate to increased insulin resistance and diabetes in the aged.

Increasing evidence also implicated telomeres in the pathogenesis of age-related disorders. Telomeres are nucleoprotein complexes at chromosome ends that function to preserve chromosomal integrity and quell p53-dependent DNA damage and DNA repair activity at these free ends. In the absence of telomerase, continued cell division results in telomere shortening, loss of ‘capping’ function, and p53 activation. The prevailing view of how uncapped telomeres compromise organ function posits that p53 mediates cellular checkpoints of growth arrest, senescence and apoptosis in stem/progenitor cells. Correspondingly, p53 deficiency ameliorates these phenotypes, particularly in organs with high proliferative demands supported by resident stem cells. The relevance of p53 in ageing is evidenced by stem cell depletion and premature ageing in mice engineered with hyper-active p53 alleles. Whereas stem/progenitor cell failure due to p53-mediated cellular checkpoints may underlie compromise of highly proliferative organs, this mechanism seems inadequate to explain the profound physiological decline in more quiescent tissues, for example, heart (cardiomyopathy) and liver (reduced detoxification capacity, glucose intolerance). These pathologies indicate that telomere dysfunction elicits a degenerative state via additional mechanisms beyond the classical senescence and apoptosis checkpoints.


Sahin E, Colla S, Liesa M, et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 2011;470(7334):359-65. Telomere dysfunction induces metabolic and mitocho... [Nature. 2011] - PubMed result / http://www.jenage.de/assets/library/pdfs/sahin_et_al_NATURE_2011.pdf

Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1alpha and PGC-1beta, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. In the setting of telomere dysfunction, enforced Tert or PGC-1alpha expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1alpha and PGC-1beta promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere-p53-PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction.


________________________________________

A Blood Test Offers Clues to Longevity
http://www.nytimes.com/2011/05/19/business/19life.html

By ANDREW POLLACK
Published: May 18, 2011

Want to know how long you will live?

Blood tests that seek to tell people their biological age — possibly offering a clue to their longevity or how healthy they will remain — are now going on sale.

But contrary to various recent media reports, the tests cannot specify how many months or years someone can expect to live. Some experts say the tests will not provide any useful information.

The tests measure telomeres, which are structures on the tips of chromosomes that shorten as people age. Various studies have shown that people with shorter telomeres in their white blood cells are more likely to develop illnesses like cancer, heart disease and Alzheimer’s disease, or even to die earlier. Studies in mice have suggested that extending telomeres lengthens lives.

Seizing on that, laboratories are beginning to offer tests of telomere length, setting off a new debate over what genetic tests should be offered to the public and what would be the ethical implications if the results were used by employers or others.

Some of the laboratories offering the tests emphasize that the results are merely intended to raise a warning flag.

“We see it as a kind of wake-up call for the patient and the clinician to say, ‘You know, you’re on a rapidly aging path,’ ” said Otto Schaefer, vice president for sales and marketing at SpectraCell Laboratories in Houston, which offers a test for $290.

A company in Spain, provocatively named Life Length, has begun selling a test for 500 euros ($712), that says that it can tell people their biological age, which may not correspond to their chronologic age.

Another company, Telome Health of Menlo Park, Calif., plans to begin offering a test later this year for about $200. It was co-founded by Elizabeth H. Blackburn of the University of California, San Francisco, who shared a Nobel Prize in 2009 for discoveries related to telomeres.

Calvin B. Harley, the chief scientific officer at Telome Health, said the test would be akin to a car’s dashboard signal, a “check engine light.” He compared it with a cholesterol test, but more versatile since it can predict a risk of various illnesses, not just heart attacks.

But among the critics of such tests is Carol Greider, a molecular biologist at Johns Hopkins University, who was a co-winner of the Nobel Prize with Dr. Blackburn.

Dr. Greider acknowledged that solid evidence showed that the 1 percent of people with the shortest telomeres were at an increased risk of certain diseases, particularly bone marrow failure and pulmonary fibrosis, a fatal scarring of the lungs. But outside of that 1 percent, she said, “The science really isn’t there to tell us what the consequences are of your telomere length.”

Dr. Greider said that there was great variability in telomere length. “A given telomere length can be from a 20-year-old or a 70-year-old,” she said. “You could send me a DNA sample and I couldn’t tell you how old that person is.”

Dr. Peter Lansdorp, a telomere expert at the British Columbia Cancer Agency, also had doubts. “If telomeres are short for you or me, what does it mean?” he said. Dr. Lansdorp started a company, Repeat Diagnostics, which conducts telomere testing for medical researchers only.

Recent media reports speculated on the tests and their possible implications, including ethical problems.

“You could imagine insurance companies wanting this knowledge to set rates or deny coverage,” said Jerry W. Shay, a professor of cell biology at the University of Texas Southwestern Medical Center in Dallas, who is an adviser to Life Length.

Test vendors say the speculation is running wild.

“It doesn’t mean we will tell anyone how long they will live,” said María Blasco, a co-founder of Life Length and a molecular biologist at the Spanish National Cancer Research Center in Madrid. Even if a 50-year-old has the telomere length more typical of a 70-year-old, she said, “This doesn’t mean your whole body is like a 70-year-old person’s body.”

Still, she said, “We think it can be helpful to people who are especially keen on knowing how healthy they are.”

Generally tests offered by a single laboratory do not have to be approved by the Food and Drug Administration. But the F.D.A. has been cracking down recently on some tests offered to the public, saying they may need approval. The FDA said in a statement Wednesday that it was aware of the tests, and had not come to any conclusions.

Executives at both Telome Health and Life Length say they will require a doctor to be involved in ordering the test, though SpectraCell said it allowed individuals to order the test.

Telomeres are stretches of DNA linked to certain proteins that are at the ends of chromosomes. They are often likened to the caps at the end of shoelaces. Each time a cell divides, the telomeres get shorter. Eventually, the telomeres get so short that the cell can no longer divide. It enters a state of senescence or dies.

One study in Utah, using blood samples from 143 elderly people collected in the 1980s, found that those with shorter telomeres were almost twice as likely to die in the ensuing years as those with longer ones.

Another study, published in The Journal of the American Medical Association last July, followed 787 people in Italy, all initially free of cancer. Those with the shortest telomeres had three times the risk of developing cancers in the next 10 years as those with the longest telomeres.

Still, not all studies have found such strong correlations. In any case, correlations do not prove that the shorter telomeres are causing the problems, although experts say some animal and cell studies do suggest causality.

Some say that the telomere test might not tell people much that cannot be learned in other ways.

“You can pretty much look at people and determine their biological age,” said Michael West, who founded Geron, the biotechnology company that sponsored and conducted some important research on telomeres. He now runs BioTime, another biotechnology company.

It is also unclear what to do about short telomeres. At the moment, there is no drug that can lengthen telomeres, though researchers are working on drugs and stem cell therapies.

There is some evidence, however, that stress is associated with shorter telomeres and that stress relief, exercise or certain nutrients such as omega-3 fatty acids might at least slow the decline in telomere length. But healthy lifestyles are already recommended for people without having to know their telomere length.

There are also disputes about how to measure telomeres. Life Length says its technique, while more expensive, can detect not only average telomere length but the shortest telomeres in cells. The shortest telomeres cause the health problems, said Dr. Shay, the adviser to Life Length.

Telome Health and SpectraCell use a DNA amplification technique called polymerase chain reaction, or P.C.R., which is cheaper but provides only an average length. And there are some questions about the accuracy.

Dr. Harley of Telome said the P.C.R. test was more relevant because virtually all the studies correlating telomere length with disease had used that test.

For those wanting to know how long they might live, there are already some indexes that are used by geriatricians to estimate the chances of a patient dying in anywhere from six months to nine years. A patient with a short expected lifespan, for instance, might no longer need to undergo annual screening for cancer.

These estimates rely on factors such as person’s age, gender, smoking history, whether they have certain diseases and whether they can perform certain functions, like walking several blocks, pushing an armchair or managing their finances.

Dr. Sei Lee, an assistant professor at the University of California, San Francisco who developed a test that estimates the probability of dying within four years, said he was not sure how much telomere length testing would add. “The chance of any single factor being a great predictor is probably low,” he said.

 

[Michael Scally MD]

Heidinger BJ, Blount JD, Boner W, Griffiths K, Metcalfe NB, Monaghan P. Telomere length in early life predicts lifespan. Proceedings of the National Academy of Sciences.

The attrition of telomeres, the ends of eukaryote chromosomes, is thought to play an important role in cell deterioration with advancing age. The observed variation in telomere length among individuals of the same age is therefore thought to be related to variation in potential longevity. Studies of this relationship are hampered by the time scale over which individuals need to be followed, particularly in long-lived species where lifespan variation is greatest. So far, data are based either on simple comparisons of telomere length among different age classes or on individuals whose telomere length is measured at most twice and whose subsequent survival is monitored for only a short proportion of the typical lifespan. Both approaches are subject to bias. Key studies, in which telomere length is tracked from early in life, and actual lifespan recorded, have been lacking. We measured telomere length in zebra finches (n = 99) from the nestling stage and at various points thereafter, and recorded their natural lifespan (which varied from less than 1 to almost 9 y). We found telomere length at 25 d to be a very strong predictor of realized lifespan (P < 0.001); those individuals living longest had relatively long telomeres at all points at which they were measured. Reproduction increased adult telomere loss, but this effect appeared transient and did not influence survival. Our results provide the strongest evidence available of the relationship between telomere length and lifespan and emphasize the importance of understanding factors that determine early life telomere length.

 

[zkt]

Seems like you have studied the telomere situation well.
Where do I put my money?

 

[Michael Scally MD]

American Society of Human Genetics
ASHG 2012 Meeting Abstract/Presentation Search and Itinerary Planner
http://www.ashg.org/2012meeting/abstracts/fulltext/


The Kaiser Permanente/UCSF Genetic Epidemiology Research Study on Adult Health and Aging: Demographic and Behavioral Influences on Telomeres and Relationship with All-cause Mortality.
Abstract/Presentation

Telomere shortening is a biomarker of aging, but it is still unclear whether it plays a direct causal role in aging-related health changes and mortality. Mendelian syndromes and heritability studies demonstrate the biological underpinnings of telomere length (TL), yet other studies show that environmental and behavioral factors also influence telomere lengths.

The Genetic Epidemiology Research Study on Adult Health and Aging (GERA) multi-ethnic cohort (average age = 63 years) has measured TL from saliva samples on over 100,000 individuals with linked electronic medical records. A detailed survey of demographic and behavioral factors was conducted 2 years prior to saliva collection, providing a unique opportunity to address questions of telomere epidemiology and aging. With these data, we examine demographic relationships with TL, behavioral influences, and relationship of TL with all-cause mortality following sample collection.

As expected, TL is inversely correlated with age, and women have longer telomeres than men except as young adults. All analyses controlled for age and gender. As seen in other studies, we find significantly longer TL among African Americans than other groups, but no significant difference between whites, Latinos and Asians. TL is positively correlated with level of education and body mass index (BMI), and negatively correlated with cigarette smoking and alcohol consumption.

All the above factors were independently significant in multivariate as well as univariate analyses. No associations were found with physical activity. We also found no relationship with diagnosis of major depression or stress-related disorders, even when limited to recent episodes.

We found that short TL was prospectively associated with mortality, although only those with the shortest TL were at increased risk; the association persisted even after adjustment of the demographic and behavioral factors such as age, sex, race, education, physical activity, BMI, smoking, and alcohol consumption.

In summary, while we found a broad range of demographic and behavioral factors that influence TL, a significant relationship of TL with mortality persisted after adjustment for all these factors. While this could indicate a direct effect of TL on health, it will also be important to examine the extent of pre-existing morbidities in these individuals to understand their possible role in the pathway between TL and longevity.

 

[Michael Scally MD]

Telomere Length In Human Blood Cells And The Prediction Of Survival
Abstract/Presentation

Telomere length (TL) in human leukocytes declines with age and several studies have shown that decreased TL is associated with increased mortality, although not in all studied populations. Previous studies had a relatively small sample size and follow-up in larger populations is warranted. In addition, it is not clear whether telomere shortening measured in blood cells marks merely a history of cell division induced by infections or whether there is a causal contribution of length reduction to mortality.

We measured TL in peripheral blood of 870 nonagenarian siblings (mean age 93 years), 1,580 of their offspring (mean age 59 years) and 725 spouses thereof (mean age 59 years.) from the Leiden Longevity Study. These participants have been followed up for vital status during 7.56 years on average.

Mean TL was measured as a ratio (T/S) of telomere repeat length (T) to the copy number (S) of the single-copy gene 36B4. There was no difference in TL between the offspring and spouses (P = 0.927), so we could analyse them as one group. Survival analysis, using Cox regression, in the nonagenarians showed that longer telomeres are associated with better survival into very old age (HR = 0.66, P = 0.028). This effect is even more pronounced in the offspring and their spouses (HR = 0.24, P = 0.001).

To determine whether the association could be based on TL marking a history of infections, we determined the association between TL and markers for immune response (white blood cell counts, hsCRP and incidence of CMV infection) and a marker for cell replication (IGF1/IGFBP3) in the offspring and spouses.

We conclude that decreased TL is significantly associated (P < 0.05) with decreased neutrophil counts, basophil counts and IGF1/IGFBP3 ratio, increased lymphocyte counts and a higher incidence of CMV infection. When the survival analysis of TL among the nonagenarians was adjusted for the mentioned parameters of cell replication and immune response, we found that TL still showed an independent association with survival (HR = 0.60, P = 0.007).

We conclude that TL predicts survival in very old and middle age and that this effect is independent from markers for immune response and cell replication. This observation is currently being replicated in independent cohorts in which we will also determine the impact of known genetic determinants of TL on survival.

 

[zazou]

I have been hearing a lot about L-carnosine being able to prevent telomere shortening. Is there any real science behind this or is it just the supplement of the month talk?