Octogenarians, Nonagenarians, & Centenarians

Discussion in 'Men's Health Forum' started by cvictorg, Jul 1, 2010.

  1. cvictorg

    cvictorg Member

    Genetic Finding May Provide a Test for Longevity
    Genetic Finding May Provide Test for Longevity - NYTimes.com

    Scientists studying the genomes of centenarians in New England say they have identified a set of genetic variants that predicts extreme longevity with 77 percent accuracy.

    The centenarians had just as many disease-associated variants as shorter-lived mortals, so their special inheritance must be genes that protect against disease, said the authors of the study, a team led by Paola Sebastiani and Thomas T. Perls of Boston University. Their report appears in Thursday’s issue of Science.

    The finding, if confirmed, would complicate proposals for predicting someone’s liability to disease based on disease-causing variants in the person’s genome, since much would depend on whether or not an individual possessed protective genes as well.

    Dr. Perls said at a press conference Wednesday that there were about 80,000 centenarians alive at any one time in the United States. Some 15 percent of his control group, and presumably of the population at large, have the potential to live to be 100, according to the test based on the 150 variants. But they fail to attain that age because of accidents or unhealthy living, he said.
     
    Last edited by a moderator: Jun 5, 2011
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Genetic Finding May Provide a Test for Longevity

    Genetic Finding May Provide a Test for Longevity
    http://www.nytimes.com/2010/07/02/science/02longevity.html

    July 1, 2010
    By NICHOLAS WADE

    If you were going to live to be 100, would you want to know it?

    When it becomes affordable to have one’s genome sequenced, perhaps in a few years, a longevity test, though not a foolproof one, may be feasible, if a new claim holds up. Scientists studying the genomes of centenarians in New England say they have identified a set of genetic variants that predicts extreme longevity with 77 percent accuracy.

    The centenarians had just as many disease-associated variants as shorter-lived mortals, so their special inheritance must be genes that protect against disease, said the authors of the study, a team led by Paola Sebastiani and Thomas T. Perls of Boston University. Their report appears in Thursday’s issue of Science.

    The finding, if confirmed, would complicate proposals for predicting someone’s liability to disease based on disease-causing variants in the person’s genome, since much would depend on whether or not an individual possessed protective genes as well.

    “I think it’s a quite striking finding,” said Nir Barzilai, an expert on longevity at the Albert Einstein College of Medicine. It shows that only a limited number of favorable genes are required to attain great age, he said. Identifying these genes would provide protection against all the diseases of old age, a more powerful strategy than tackling each disease one by one.

    “I feel there’s an elephant in the room and no one realizes it’s really important — this is the next step to make us all healthy,” Dr. Barzilai said.

    The Boston University team found the genetic variants with a statistical technique called a genome-wide association study. This is the technique that researchers had hoped would lay bare the genetic roots of common diseases like Alzheimer’s or cancer, but it has largely failed to do so, raising the question of how the Boston University team was more successful while using a smaller sample size than usual. The team analyzed the genomes of 1,055 centenarians.

    Dr. Sebastiani said the reason for their success was that living past 100 was such an extreme form of longevity that any genes involved would give very powerful signals of their presence, offsetting the reduced statistical power of the small sample.

    She found that 150 genetic variants were associated with extreme longevity. She then looked at a different sample of centenarians from those involved in her study and found that more than three-quarters possessed many of the 150 genetic variants she had already identified. The other centenarians had few or none of the protective variants, which means there are many more yet to find, Dr. Sebastiani said.

    But Kari Stefansson, a geneticist who has looked for determinants of longevity among the Icelandic population, said of the current study that he was “amazed at how many loci of genome-wide significance have been found in a modest sample size.”

    Dr. Stefansson said he had been able to accumulate a larger collection of centenarians, despite Iceland’s small population, because his company, Decode Genetics, has analyzed most of the genomes of living Icelanders and in addition can compute the genomes of Icelanders who lived long ago from the genomes of their descendants. None of the Boston University team’s 150 genetic variants is present among Icelandic centenarians, he said.

    Dr. Perls said at a press conference Wednesday that there were about 80,000 centenarians alive at any one time in the United States. Some 15 percent of his control group, and presumably of the population at large, have the potential to live to be 100, according to the test based on the 150 variants. But they fail to attain that age because of accidents or unhealthy living, he said.


    Sebastiani P, Solovieff N, Puca A, et al. Genetic Signatures of Exceptional Longevity in Humans. Science:science.1190532.

    Healthy aging is thought to reflect the combined influence of environmental factors (lifestyle choices) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity (EL) in 1055 centenarians and 1267 controls. Using these data, we built a genetic model that includes 150 single-nucleotide polymorphisms (SNPs) and found that it could predict EL with 77% accuracy in an independent set of centenarians and controls. Further in silico analysis revealed that 90% of centenarians can be grouped into 19 clusters characterized by different combinations of SNP genotypes--or genetic signatures--of varying predictive value. The different signatures, which attest to the genetic complexity of EL, correlated with differences in the prevalence and age of onset of age-associated diseases (e.g., dementia, hypertension, and cardiovascular disease) and may help dissect this complex phenotype into subphenotypes of healthy aging.
     

    Attached Files:

    Last edited: Jul 2, 2010
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Genetic Finding May Provide a Test for Longevity

    For those interested, I have attached the Science article and the supplementary material. This is available at New England Centenarian Study ? BUMC
     

    Attached Files:

    Last edited: Jul 13, 2012
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Genetic Finding May Provide a Test for Longevity

    Scientists Criticize Study on Genetics of Old Age
    http://www.nytimes.com/2010/07/09/health/research/09age.html

    July 8, 2010
    By NICHOLAS WADE

    A study on the genetics of centenarians that was published last week in Science, a leading scientific journal, has come under criticism from geneticists who say it has obvious weaknesses, is probably incorrect and should not have been published in a premier journal.

    The study, which received broad press coverage, said that 150 genetic variants predictive of longevity had been identified among New England centenarians and that a test based on those variants could predict who would live to extreme old age.

    But on Wednesday, the senior author of the report, Dr. Thomas T. Perls of Boston Medical Center, part of Boston University’s School of Medicine, said in an e-mail message that he had been “made aware that there is a technical error in the lab test” used on some of the centenarians. The results are now being re-examined, but a preliminary analysis suggests that “the apparent error would not affect the overall accuracy of the model,” he said.

    Science issued a statement on Wednesday saying that the data was being reanalyzed, but that its reviewers “determined that the statistics and the design of the study were sound.”

    The Boston University group’s results may withstand challenge. But the issue sheds light on a tangled knot of interests, starting with weekly scientific journals like Nature, Science and The New England Journal of Medicine, which are embroiled in a constant competition for reports of newsmaking scientific advances.

    Journal editors know that press coverage can burnish a journal’s reputation. Scientists, in turn, like to have their work cited in the news media because it helps draw attention to their fields and raise money. And science journalists, competing for space with political and sports news, welcome astounding claims without always kicking the tires as hard as necessary. These factors sometimes combine to give substantial publicity to scientific claims that may not fully deserve such attention.

    The Boston University study was widely reported, uncritically in many cases, after Science held a press conference about it last week. Reviews from geneticists were less enthusiastic.

    “I think it is very unlikely indeed that the findings in the Science paper are correct, or even mostly correct,” David B. Goldstein, a geneticist at Duke University, wrote last week in an e-mail message.

    “I am pretty surprised that Science carried it,” he added. “And I think this also raises an interesting, more general point, which is how the press ought to handle stuff when there are serious questions about the security of the finding.”

    Another expert, Dr. David Altshuler of Massachusetts General Hospital, explained that using different types of gene chips to scan the genome, as the Boston University researchers had done with their centenarians, was widely recognized as a source of possible problems.

    By Tuesday, another critic, Dr. Kari Stefansson of the gene-finding company Decode Genetics in Iceland, had identified what seemed to him to be the specific problem. One of the two kinds of chip used by the Boston researchers, called the Illumina 610, attributes a less common form of a gene to having come from both parents instead of just one, Dr. Stefansson said. He calculated that if only 10 percent of the Boston centenarians had been typed with this chip, it would have made the genetic variants appear associated with longevity even though they were not.

    The Boston team did not report in its article how many patients had been typed with which chip. But responding to a request, Paola Sebastiani, the group’s statistician, said in an e-mail message that 108 of the 1,055 centenarians had been tested with the Illumina 610 array, almost exactly the 10 percent that Dr. Stefansson had predicted.

    Dr. Sebastiani said that “the problem should be limited to the top two SNPs,” referring to the genetic variants the team found to be associated with extreme longevity.

    “The conclusions of this analysis, even if one or two SNPs have bad genotype data, are not going to change,” she said.

    Dr. Stefansson, however, believes the problem affects all the results, including the 33 genetic variants that the Boston University team said had been confirmed in a second study. “It is absolutely clear that there is nothing to this,” he said.

    Scientific journals cannot guarantee the truth of the reports they publish, but they do try to weed out obvious error by submitting manuscripts to expert reviewers. Dr. Sebastiani said she had performed extra analyses that “were suggested by the anonymous reviewers of the article, who were then satisfied with the results.”

    But whether because the reviewers were not rigorous enough, or because Science’s editors ignored their cautions, the result was a publication that leading experts felt had not been sufficiently scrutinized. “Accurate typing of the associated SNPs should have been required, and hence there is a very specific failing in the review process,” Dr. Goldstein said.
     
  5. cvictorg

    cvictorg Member

    Last edited by a moderator: Jun 5, 2011
  6. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    The Ikaria Island, Greece

    Demographic analyses throughout the world suggest that the oldest old (i.e., people of age 80 years and older) are the fastest growing portion of the population. Due to these changes, the United Nations' Global Population Pyramid is undertaking a shift, from the classical shape of a pyramid to a cube. The resultant change in the age distribution of the world's population has been, partially attributed to the medical advancements of the recent years, a reduction in maternal and infant mortality, as well as in improved nutrition.

    Beyond these global considerations, it is of interest that there are places around the world where people live longer and, most importantly, they are physically active even after the age of 100 years. Specifically, in the past years anthropologists observed that people living in Sardinia (Italy), Okinawa (Japan), Loma Linda (California), and Nicoya Peninsula (Costa Rica) have very high life expectancy, with the percent of people over the age of 90 being at amazing rates as compared with the developed world average rate.

    These places have been defined as the “Blue Zones” and are a part of a large anthropologic and demographic project. It has been observed that people living in these areas share common behavioral and lifestyle characteristics, despite the different race, nationality, and regional characteristics they have. Particularly, the investigators of the Blue Zones reported that “some lifestyle characteristics, like family coherence, avoidance of smoking, plant-based diet, moderate and daily physical activity, social engagement, where people of all ages are socially active and integrated into the community, are common in all people enrolled in the surveys.” Clearly, longevity is a complex attribute, determined by factors such as, exposure to disease, variability in sleeping patterns, smoking, physical activity, and dietary habits, in addition to the indirect emotional and cognitive influence on physiological pathways.

    Recently it was reported that people in Ikaria Island (in Greece) have also one of the highest life expectancies in the world. The Ikaria Island is located in the central-eastern part of Aegean Sea. The first name of Ikaria was Dolichi, but through Greek mythology it became connected to Ikarus, the first man who succeeded to fly and commemorates his fall. Total population of the Island is about 8,000 people, and the vast majority of them follow a traditional way of living (i.e., traditional dietary habits that included plant foods, daily physical activities, daily naps, mountain living, low stress). Moreover, Ikaria has eight super-hot, radioactive, saline springs, which flow at various points on the Island's shores. The history of the mineral springs is linked with that of the country. Herodotous (484–425 BC) was the first observer of curative waters. Indeed, he preceded Hippocrates (460–370 BC) and described a good number of health springs. Thus, the aim of this work was to evaluate various sociodemographic, lifestyle and psychological characteristics of oldest old (>80 years) people participated in the Ikaria Study.


    Panagiotakos DB, Chrysohoou C, Siasos G, et al. Sociodemographic and lifestyle statistics of oldest old people (>80 years) living in ikaria island: the ikaria study. Cardiol Res Pract;2011:679187. Sociodemographic and Lifestyle Statistics of Oldest Old People (>80 Years) Living in Ikaria Island: The Ikaria Study

    Background. There are places around the world where people live longer and they are active past the age of 100 years, sharing common behavioral characteristics; these places (i.e., Sardinia in Italy, Okinawa in Japan, Loma Linda in California and Nicoya Peninsula in Costa Rica) have been named the "Blue Zones". Recently it was reported that people in Ikaria Island, Greece, have also one of the highest life expectancies in the world, and joined the "Blue Zones". The aim of this work work was to evaluate various demographic, lifestyle and psychological characteristics of very old (>80 years) people participated in Ikaria Study.

    Methods. During 2009, 1420 people (aged 30+) men and women from Ikaria Island, Greece, were voluntarily enrolled in the study. For this work, 89 males and 98 females over the age of 80 yrs were studied (13% of the sample). Socio-demographic, clinical, psychological and lifestyle characteristics were assessed using standard questionnaires and procedures.

    Results. A large proportion of the Ikaria Study's sample was over the age of 80; moreover, the percent of people over 90 were much higher than the European population average. The majority of the oldest old participants reported daily physical activities, healthy eating habits, avoidance of smoking, frequent socializing, mid-day naps and extremely low rates of depression.

    Conclusion. Modifiable risk factors, such as physical activity, diet, smoking cessation and mid-day naps, might depict the "secrets" of the long-livers; these findings suggest that the interaction of environmental, behavioral together with clinical characteristics may determine longevity. This concept must be further explored in order to understand how these factors relate and which are the most important in shaping prolonged life.


    [​IMG]

    The Ikaria Island (Ikaria lies in the east Aegean, within the complex of the East Sporades, between Samos and Mykonos. Area: 255.32 km2, location: 37° 35?41.42?? N-26° 09?30.88?? E, distance from Piraeus 140 nm, coastline length: 160 km, population: 8,312. Administratively Ikaria is divided into three municipalities, the Municipality of St. Kirykos which is the capital and the south port of the island, the Municipality of Evdilos where is the north port, and the municipality of Rahes which is in the central-west part of the island. Ikaria is exclusively comprised of crystalloid schist metamorphic rocks. Ikaria's wider area has been incorporated in NATURA 2000 network for the protection of natural environments, due to its biophysical variety).
     

    Attached Files:

  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Is Telomere Length a Biomarker of Aging

    Increased inter-individual and intra-individual variability is observed within sensory, motor, and cognitive and health domains with increasing chronological age. This inter-individual and intra-individual variability is found among individuals of the same age, suggesting that chronological age is a relatively imprecise measure of an individual’s functional or health status. The concept of biomarkers of aging was developed to provide more information about an individual’s biological health or functional status than chronological age. Biomarkers of aging are quantifiable parameters that reflect biological aging, which potentially can identify those at risk of aging-related conditions, disease, and mortality. Biomarkers could also be used to monitor and evaluate interventions designed to delay the onset or retard the progression of aging-related conditions and disease. Even though there has been little agreement on the validation criteria for candidate biomarkers, the promise of the utility of biomarkers of aging continues to be a driving force for research.

    Telomere length has been proposed as a candidate biomarker of aging. Telomeres are nucleoprotein structures located at the ends of eukaryotic chromosomes. The observation that telomeres shorten with increasing age and are implicated in cellular aging has led to the proposal that telomere length is a biomarker of aging. Support for this hypothesis is provided by human studies that have found a significant inverse relationship between telomere length and several age-sensitive measures, aging-related conditions, disease, and mortality. However, the evidence is equivocal.

    In a 2005 review of the in vitro and in vivo evidence, researchers found that telomere length satisfied several criteria for a biomarker of aging, as it changes with age, has high inter-individual variability, is linked to basic biology, and correlates with aging and aging-related disease. The authors acknowledged that the majority of the evidence was cross-sectional and that many studies were underpowered.

    Since this review, a wide range of human studies have been published examining the relationship of telomere length with aging-related measures and mortality, prompting the need to reexamine the evidence using a set of well-defined biomarker of aging criteria developed by the American Federation of Aging Research:

    1. It must predict the rate of aging. In other words, it would tell exactly where a person is in their total life span. It must be a better predictor of lifespan than chronological age.

    2. It must monitor a basic process that underlies the aging process, not the effects of disease.

    3. It must be able to be tested repeatedly without harming the person. For example, a blood test or an imaging test.

    4. It must be something that works in humans and in laboratory animals, such as mice. This is so that it can be tested in lab animals before being validated in humans.



    Mather KA, Jorm AF, Parslow RA, Christensen H. Is Telomere Length a Biomarker of Aging? A Review. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2011;66A(2):202-13. Is Telomere Length a Biomarker of Aging? A Review

    Telomeres, the DNA-protein structures located at the ends of chromosomes, have been proposed to act as a biomarker of aging. In this review, the human evidence that telomere length is a biomarker of aging is evaluated. Although telomere length is implicated in cellular aging, the evidence suggesting telomere length is a biomarker of aging in humans is equivocal. More studies examining the relationships between telomere length and mortality and with measures that decline with "normal" aging in community samples are required. These studies would benefit from longitudinal measures of both telomere length and aging-related parameters.
     
  8. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Sebastiani group retracts genetics of aging study from Science
    Sebastiani group retracts genetics of aging study from Science Retraction Watch

     
  9. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    The World's Deadliest Distinction
    Why aren't the oldest living people getting any older?
    Why aren't the oldest living people getting any older? - By Will Oremus - Slate Magazine


     
  10. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Living to 100 and Beyond
    Scientists are on the brink of radically expanding the span of a healthy life. Author Sonia Arrison on the latest advances—and what they mean for human existence.
    Living to 100 and Beyond - WSJ.com

    In Jonathan Swift's "Gulliver's Travels," Gulliver encounters a small group of immortals, the struldbrugs. "Those excellent struldbrugs," exclaims Gulliver, "who, being born exempt from that universal calamity of human nature, have their minds free and disengaged, without the weight and depression of spirits caused by the continual apprehensions of death!"

    But the fate of these immortals wasn't so simple, as Swift goes on to report. They were still subject to aging and disease, so that by 80, they were "opinionative, peevish, covetous, morose, vain, talkative," as well as "incapable of friendship, and dead to all natural affection, which never descended below their grandchildren." At 90, they lost their teeth and hair and couldn't carry on conversations.

    For as long as human beings have searched for the fountain of youth, they have also feared the consequences of extended life. Today we are on the cusp of a revolution that may finally resolve that tension: Advances in medicine and biotechnology will radically increase not just our life spans but also, crucially, our health spans.

    The number of people living to advanced old age is already on the rise. There are some 5.7 million Americans age 85 and older, amounting to about 1.8% of the population, according to the Census Bureau. That is projected to rise to 19 million, or 4.34% of the population, by 2050, based on current trends. The percentage of Americans 100 and older is projected to rise from 0.03% today to 0.14% of the population in 2050. That's a total of 601,000 centenarians.

    But many scientists think that this is just the beginning; they are working furiously to make it possible for human beings to achieve Methuselah-like life spans. They are studying the aging process itself and experimenting with ways to slow it down by way of diet, drugs and genetic therapy. They are also working on new ways to replace worn-out organs—and even to help the body to rebuild itself. The gerontologist and scientific provocateur Aubrey de Grey claims that the first humans to live for 1,000 years may already have been born.

    The idea of "conquering" aging has raised hopes, but it has also spurred a debate about whether people should actually aspire to live that long. What does a longer-living population mean for relationships and families? How can we afford to support massive numbers of aging citizens, and how can individuals afford to support themselves? Won't a society of centenarians just be miserable, tired and cranky?

    The scientists working on these issues respond to such concerns by stressing that their aim is not just to increase the quantity of life but its quality as well. A life span of 1,000 may be optimistic, they suggest, but an average span of 150 years seems well within reach in the near future, with most of those years being vital and productive.

    One key area of research is gene therapy. Cynthia Kenyon of the University of California, San Francisco, found that partially disabling a single gene, called daf-2, doubled the life of tiny worms called Caenorhabditis elegans. Altering the daf-16 gene and other cells added to the effect, allowing the worms to survive in a healthy state six times longer than their normal life span. In human terms, they would be the equivalent of healthy, active 500-year-olds.

    Experiments with animals are not always applicable to humans, of course, but humans do have the same sort of genetic pathways that Dr. Kenyon manipulated. Other researchers have made similar findings. A laboratory at the University of Arkansas genetically altered worms to live 10 times longer than normal. Spain's National Cancer Research Center found an altogether different way to extend the lives of mice by 45%.

    Other scientists are working to repair and replace worn-out body parts. The Wake Forest Institute for Regenerative Medicine, led by Anthony Atala, has successfully grown bladders in a lab and implanted them in children and teenagers suffering from a congenital birth defect. The basic structure of the bladders was built using biodegradable materials and was then populated with stem cells from the patients, so that their bodies wouldn't reject the transplant. It worked. Today the institute is working to grow more than 30 different organs and tissues, including livers, bone and hearts.

    With heart disease the No. 1 killer in the U.S., building a human heart will be a major step forward. Doris Taylor announced in 2008 that her cardiovascular lab at the University of Minnesota had managed to grow a rat heart using a technique similar to Dr. Atala's, except that the structure she used was from a donor rat. Dr. Taylor is currently repeating the experiment on pigs, not only because their hearts are closer in size to human hearts but also because pig hearts are already used for replacement parts for some human heart patients.

    Another promising new technology is organ printing, which is exactly what it sounds like: Cells, rather than ink, are put into a sophisticated 3-D printer and then printed onto a biodegradable material. The machine prints "pages" of cells on top of each other to make a three-dimensional shape. In December 2010, a company called Organovo announced that it had successfully printed human blood vessels—an important feature of all organs.

    At the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, Stephen Badylak is working with "extracellular matrix"—the material that gives structure to tissue—from pig bladders. Dr. Badylak has used ECM to grow back the tips of patients' fingers that have been accidentally snipped off, and his colleagues have used it to cure early-stage esophageal cancer by removing the cancerous cells and replacing them with ECM. Scientists don't yet understand why the substance promotes new tissue growth, and ECM can't yet grow back entire limbs, but the results so far are impressive.

    Assuming that the necessary technology eventually arrives, the big question is: What will life look like when we live to over 100?

    One of the most important areas of potential change is family and relationships. With an average life expectancy of 150 years, it's possible that we might see age differences of as much as 80 or 90 years between spouses and partners. But the historical evidence suggests that such disparities in age probably won't be common.

    Research by Norway's government statistics bureau shows that between 1906 and 2002, life expectancy rose from around 57 years to around 79 years in that country. But the average age difference in relationships remained at around 3.5 years (men being slightly older).

    One reason for the rarity of relationships with large age gaps is that modern societies tend to look down on them. Will the number of men marrying much younger women continue to grow as people live longer and such relationships become less stigmatized?

    Research done at Stanford, the University of California, Santa Barbara, and the University of Wisconsin suggests that older men seek younger partners primarily to continue having children. If that is the case, such men won't need to find younger partners once it is easier for older women to have their own biological children using new fertility technologies.

    And in the future, older women (and men) will likely look less "aged" because they will remain healthy for much longer. Remarriage for beauty or youth will lose some of its distinguishing force.

    More time to live also raises the possibility of more divorces and remarriages—the seven-year itch turned into the 70-year itch. Today, some people get married two or even three times, but as people live longer, these numbers could increase, perhaps exceeding Liz Taylor proportions for at least a small slice of the population. But greater longevity might also lead to a higher incidence of serial monogamy, regardless of whether it leads to marriage, perhaps interspersed with periods of living alone.

    As researchers further refine reproductive technology like egg freezing and ovary transplants, the ranks of older parents, currently on the rise, are bound to increase even more. This raises the prospect of families in which siblings are born many decades apart, perhaps 50 years or more. How would such age gaps between children change family dynamics?

    We know that siblings of the same age cohort have more meaningful and longer-lasting relationships than those separated by more years, but it is difficult to predict how the relationship between siblings born decades apart would function. It probably would be akin to that of a child and an aunt or uncle, or even a child and a grandparent.

    Living longer would also mean both making and spending money longer. What would an economy look like in which work lives extended into a second century of potential productivity?

    Most of us already don't expect to retire at 65. The Social Security system cannot afford it even now, and in the future, going out to pasture at 65 will mean decades of boredom. People who live to 150 will use their additional years for second and third careers, and we are likely to see a greater movement toward part-time and flex-time work.

    It has long been clear that wealth creates health. We now know that health also begets wealth. In a paper titled "The Health and Wealth of Nations," Harvard economist David Bloom and Queen's University economist David Canning explain that, based on the available research, if there are "two countries that are identical in all respects, except that one has a five-year advantage in life expectancy," then the "real income per capita in the healthier country will grow 0.3–0.5% per year faster than in its less healthy counterpart."

    Although these percentages might look small, they are actually quite significant, especially when we consider that between 1965 and 1990 countries experienced an average per capita income growth of 2% per year.

    Those numbers are based on only a five-year longevity advantage. What if a country had a 10-, 20-, or 30-year advantage? The growth might not continue to rise in linear fashion, but if the general rule holds—a jump in life expectancy causes an increase in economic growth per capita—then having a longer-lived population would generate enormous differences in economic prosperity.

    In a 2006 study, the University of Chicago economists Kevin Murphy and Robert Topel painstakingly calculated that for Americans, "gains in life expectancy over the century were worth over $1.2 million per person to the current population." They also found that "from 1970 to 2000, gains in life expectancy added about $3.2 trillion per year to national wealth."

    The world's advanced societies are finally in a position to launch a true offensive against the seemingly irresistible terms imposed on our lives by disease and death. That's good news for us as individuals and for humanity as a whole. A longer span of healthy years will lead to greater wealth and prospects for happiness.

    But realizing the full potential of the longevity revolution will not be easy. We will need to tackle important and legitimate questions about the effects of greater health spans on population growth, resource availability and the environment. The decisions that we make in this regard will matter far more than the mere fact of greater numbers.

    The very idea of radically greater longevity has its critics, on the right and the left. Leon Kass, who served as chairman of the President's Council on Bioethics under George W. Bush, sees the scientific effort to extend life as an instance of our hubris, an assault on human nature itself.

    The environmental writer Bill McKibben, for his part, strongly opposes what he calls "techno-longevity," arguing that "like everything before us, we will rot our way back into the woof and warp of the planet."

    I'm unconvinced. Arguments against life extension are often simply an appeal to the status quo. If humans were to live longer, we are told, the world, in some way, would not be right: It would no longer be noble, beautiful or exciting.

    But what is noble, beautiful and exciting about deterioration and decline? What is morally suspect about ameliorating human suffering?

    The answer is nothing. Everything that we have, socially and as individuals, is based on the richness of life. There can be no more basic obligation than to help ourselves and future generations to enjoy longer, healthier spans on the Earth that we share.
     
  11. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Number Of Centenarians In Japan Tops 47,000
    Number Of Centenarians In Japan Tops 47,000

     
  12. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Purging Old Cells Is Found to Slow Aging in Mice
    http://www.nytimes.com/2011/11/03/s...g-but-can-be-purged-mouse-study-suggests.html

    November 2, 2011
    By NICHOLAS WADE

    In a potentially fundamental advance, researchers have opened up a novel approach to combating aging with the discovery that a special category of cells, known as senescent cells, are bad actors that promote the aging of the tissues. Cleansing the body of the cells, they hope, could postpone many of the diseases of aging.

    Senescent cells accumulate in aging tissues, like arthritic knees, cataracts and the plaque that may line elderly arteries. The cells secrete agents that stimulate the immune system and cause low-level inflammation. Until now, there has been no way to tell if the presence of the cells is good, bad or indifferent.

    The answer turns out to be that the cells hasten aging in the tissues in which they accumulate. In a delicate feat of genetic engineering, a research team led by Darren J. Baker and Jan M. van Deursen at the Mayo Clinic in Rochester, Minn., has generated a strain of mouse in which all the senescent cells can be purged by giving the mice a drug that forces the self-destruction of just these cells.

    Rid of the senescent cells, the Mayo Clinic researchers reported online Wednesday in the journal Nature, the mice’s tissues showed a major improvement in the usual burden of age-related disorders. Mice that had been cleansed of senescent cells from weaning onward did not develop cataracts, avoided the usual wasting of muscle with age, and could exercise much longer on a mouse treadmill. They retained the fat layers in the skin that usually thin out with age and, in people, cause wrinkling.

    The experiment holds promise for humans, the scientists said. Their findings indicate that any therapy that rids the body of senescent cells would delay age-related changes.

    “I am very excited by the results,” said Dr. Norman E. Sharpless, an expert on aging at the University of North Carolina. “It suggests therapies that might work in real patients,” he said.

    Dr. van Deursen’s work is the first to show that removing senescent cells is beneficial. If confirmed, it “will be considered a fundamental advance by our field,” Dr. Sharpless said.

    Judith Campisi, at the Buck Institute for Research on Aging, said the new finding was the first proof that senescent cells can drive the aging process. “So it’s really quite a breakthrough,” she said.

    In both mice and people, senescent cells are few in number but have major effects on the body’s tissues. Killing the cells should therefore have large benefits with little downside. The gene-altering approach used on the mice cannot be tried in people, but now that senescent cells appear to be harmful, researchers can devise ways of targeting them.

    Drugs already exist to combat some of the inflammatory hormones secreted by senescent cells. The body’s immune system, which probably clears away senescent cells all the time but does so less efficiently with age, could perhaps be trained to attack senescent cells more aggressively. Or researchers could one day develop specific drugs to kill the cells, when the differences between ordinary and senescent cells are better understood.

    Dr. van Deursen said he thought it worth trying to eliminate senescent cells after the finding that they reliably switch on a gene known as p16-Ink4a. In the research mice, he arranged for another gene, which also switches on p16-Ink4a, to simultaneously prime a mechanism to make the cell self-destruct. Thus whenever a cell became senescent, it also armed a self-destruct mechanism. The mechanism fired only when the mice were dosed with a specific drug. The result was that only senescent cells were at risk from the drug, and that they could be purged at any desired time in the mouse’s lifetime.

    In a second experiment, the mice were not given the cell-cleaning drug until they were middle-aged. Their cataracts had already developed by then and were irreversible, but aging was delayed in their fat and muscle tissues.

    It may be that senescent cells are beneficial in youth but harmful in old age, when the immune system seems to clear them less rapidly from the body. The second mouse experiment suggests that middle age would be an effective time for clinical intervention, assuming humans behave in the same way.

    If aging of the tissues is delayed by eliminating senescent cells, the mice should, in principle, have lived longer. Dr. van Deursen said this was not the case in this experiment only because he had chosen a fast-aging strain of mice to get a quick result. These particular mice succumb to heart attacks at an early age, regardless of the state of their tissues. The Mayo Clinic team plans to repeat its experiment with an ordinary strain of mouse that normally lives three years or more, to see if its life span is extended as expected with treatment.

    The Mayo Clinic finding “is a really important step forward for the field,” said Dr. Campisi of the Buck Institute.

    The purpose of research on aging is not to let people live a thousand years, as portrayed in science fiction, but to increase health span, the proportion of people’s natural lives that they live in good health.

    “People used to see aging as a rusting nail — there’s nothing you can do about it,” Dr. Campisi said. “But we now know that there are processes that are driving aging, and that those processes can be meddled with.”


    Baker DJ, Wijshake T, Tchkonia T, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature;advance online publication. http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10600.html

    Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells1, 2. Senescent cells accumulate in various tissues and organs with ageing3 and have been hypothesized to disrupt tissue structure and function because of the components they secrete4, 5. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16Ink4a, to design a novel transgene, INK-ATTAC, for inducible elimination of p16Ink4a-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16Ink4a-positive senescent cells upon drug treatment. In tissues—such as adipose tissue, skeletal muscle and eye—in which p16Ink4a contributes to the acquisition of age-related pathologies, life-long removal of p16Ink4a-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.
     
  13. zkt

    zkt Member

    "If you were going to live to be 100, would you want to know it?

    If I knew I was going to live THIS long I would have taken better care of the body a long time ago !


    Read more from the MESO-Rx Steroid Forum at: http://forum.mesomorphosis.com/mens-health-forum/octogenarians-nonagenarians-and-centenarians-134293235.html#ixzz1cap9Q5MA"
     
  14. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Lawler DF. The changing understanding of ageing. Part 1: Evaluating ageing theories and studies. Vet Ital 2011;47(3):229-40. http://www.izs.it/vet_italiana/2011/47_3/229.pdf

    This is the first of three discussions on emerging views of ageing, its derivation, and ageing-related diseases. To offer a context for the series, this first report briefly reviews several major early and recent theoretical debates. Arguments for and against several well-known ageing theories are presented for their veterinary relevance, including mutation, pleiotropy, reproduction-longevity trade-offs, oxygen metabolism and ageing as a genomically programmed product of natural selection. Additionally, the author presents commonly encountered problems when reading to interpret laboratory and population studies of ageing, offering busy clinicians a perspective on evaluating complex papers that analyse ageing-related data. Included among these problems are categorising intrinsic and extrinsic diseases, contrasts between laboratory-based and population-based observations, over-generalising research outcomes, short-term and long-term studies, and theoretical treatises. Central ideas of these discussions include why post-reproductive life span is relatively common among animals, the nature of age-related diseases relative to stochastic or programmed origins and the disease-related implications.

    Lawler DF. The changing understanding of ageing. Part 2: Body composition, metabolism and cell death. Vet Ital 2011;47(3):241-53. http://www.izs.it/vet_italiana/2011/47_3/241.pdf

    This second of three discussions about ageing biology and diseases continues at the level of the organism, examining the relationship among body composition, late life and diseases. One view of significant age-related mass loss in humans suggests that anabolic failure is associated with various precipitating factors that may share anorexia in common. Lean mass decline with even partial anorexia should alert clinicians to monitor patients for emergence of otherwise subclinical disease. Weight or mass loss and clinical disease also may be independent, thus creating an interwoven and complex view. Recent data from the Portuguese water dog genetics model suggest that heritable factors play a role in end of life body metrics and some histological changes, and that some metric and histological changes are themselves inter-related. While widespread inflammation and hyperplasia were less frequent than expected, there exists nonetheless a disease relationship to the growth hormone (GH)-insulin-like growth factor (igf-1)-insulin axis that requires further exploration. Oxidative metabolism and apoptosis are reviewed briefly as examples at the cellular level that may be reflected in gross ageing phenotypes, further underscoring the complex nature of many late-life diseases.

    Lawler DF. The changing understanding of ageing. Part 3: Diseases of ageing. Vet Ital 2011;47(3):255-69. http://www.izs.it/vet_italiana/2011/47_3/255.pdf

    This third and final paper in this series considers ageing mechanisms across species, with emphasis on conserved metabolic pathways that relate to disease. The growth hormone (GH)-insulin-like growth factor (IGF-1)-insulin axis continues as an example of how critical pathways might relate to longevity and senescence. Aligning theory, research outcomes and clinical investigations at the levels of the cell, organism and population, is suggested as a means by which to consider the many complexities of the ageing process in an orderly fashion. A contentious debate revolves around whether ageing is purely a combined effect of stochastic events on residual programming relating to reproductive robustness, or whether ageing itself is programmed by natural selection. Emerging data indicate that the influence of genetic programming on specific late-life diseases, and even individual tissue pathologies, will probably need to be reconsidered in the light of newer theoretical possibilities. In particular, the evidence that late life and its diseases are objects of considerable investment of energy challenges theory that couples longevity with reproduction. Furthermore, the author suggests that ageing may have evolved at least partly as a means of niche preservation for contemporaries and for progeny.
     
  15. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Discovery of Functional Gene Variants Associated With Human Longevity

    Rather than driven by stochastic events alone and being a simple entropic process of deterioration, the rate of aging and life span have been shown to be regulated by multiple pathways. Many single-gene mutations identified in invertebrates result in a reduced rate of aging and an increased life span. A large fraction of these mutations extends life span in mammals as well. These studies have provided important clues for discovering the evolutionarily conserved pathways of life span and their impact on the aging rate. Altering the pathways controlling metabolism, endocrine signaling, nutrient sensing, stress resistance, and telomere maintenance has been shown to prolong life span from yeast to mammals.

    Among those conserved pathways, the insulin/insulin-like growth factor-1 (igf-1) signaling (IIS) pathway was the first one shown to regulate life span in animal models and also had the most profound effect on life-span extension. In brief, binding of IGF-1 and insulin activates an intracellular signaling cascade composed of IRS-1/PI3K/AKT that antagonizes the activity of Forkhead/FOXO transcription factors. Reduction-of-function mutations in IIS genes activate Forkhead/FOXO proteins that regulate expression of several hundred genes implicated in metabolism, stress resistance, and antimicrobial defense. Remarkably, these long-lived animals maintain their youthfulness and display delayed signs of aging and a late onset of age-related diseases. Continued discoveries of beneficial effects of mutations on many aspects of aging in long-lived animals support the concept that aging is a major risk factor for many common human diseases and that targeting aging is a logical and economically sound strategy in developing new targets for prevention and early-stage treatment.

    [​IMG]



    Insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS) is a major candidate pathway in human longevity. Binding of IGF-1 or insulin (INS) initiates the evolutionarily conserved IRS–PI3K–AKT signaling cascade to phosphorylate Forkhead transcription factor FOXO. When phosphorylated, FOXO is retained in the cytoplasm. Mutations perturbing the IIS pathway reduce phosphorylation of FOXO, enabling it to enter the nucleus and regulate transcription of diverse genes that collectively contribute to the extension of life span. The role of reduced IIS in life-span extension is well-established in model organisms from yeast to mammals, suggesting that altered IIS may also influence human life span. Human population studies established genetic associations between some of the IIS genes, for example, IGF1R, AKT, FOXO3a, and longevity, supporting the role of IIS pathway in human longevity.


    Tazearslan C, Cho M, Suh Y. Discovery of Functional Gene Variants Associated With Human Longevity: Opportunities and Challenges. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2012;67A(4):376-83. http://biomedgerontology.oxfordjournals.org/content/67A/4/376.full.pdf

    Age is a major risk factor for many human diseases. Extremely long-lived individuals, such as centenarians, have managed to ward off age-related diseases and serve as human models to search for the genetic factors that influence longevity. The discovery of evolutionarily conserved pathways with major impact on life span in animal models has provided tantalizing opportunities to test the relevance of these pathways for human longevity. Here we specifically focus on the insulin/insulin-like growth factor-1 signaling as a prime candidate pathway. Coupled with the rapid advances in ultra high-throughput sequencing technologies, it is now feasible to comprehensively analyze all possible sequence variants in candidate genes segregating with a longevity phenotype and to investigate the functional consequences of the associated variants. A better understanding of the functional genes that affect healthy longevity in humans may lead to a rational basis for intervention strategies that can delay or prevent age-related diseases.
     

    Attached Files:

    • 100.gif
      100.gif
      File size:
      65 KB
      Views:
      34
  16. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Lester Breslow, Who Linked Healthy Habits and Long Life, Dies at 97
    http://www.nytimes.com/2012/04/15/h...tied-good-habits-to-longevity-dies-at-97.html

    April 14, 2012
    By DOUGLAS MARTIN

    Dr. Lester Breslow, a public health leader whose research gave mathematical proof to the notion that people can live longer and healthier by changing habits like smoking, diet and sleep, died Monday at his home in Los Angeles. He was 97.

    The University of California, Los Angeles, where Dr. Breslow was a former dean of the Fielding School of Public Health, announced the death.

    Dr. Breslow’s most lauded accomplishment was a study of 6,928 people in Alameda County, Calif., that examined their behavior over intervals of up to 20 years. It used quantitative analysis to prove that a 45-year-old with at least six of the seven healthy habits Dr. Breslow chose as important had a life expectancy 11 years longer than someone with three or fewer.

    Over a 70-year career, Dr. Breslow helped expand the very definition of public health, from the historical concentration on communicable disease to a new concern with individual behavior and the effects of community and environment. As people lived longer and had more cancer and heart attacks, he was a leader in emphasizing the mounting importance of chronic disease.

    “He changed the way we thought of public health,” said Dr. Linda Rosenstock, the current dean of the Fielding School. His message, she said, was that “the root causes of our health problems are broader than our own biology.”

    In 1952, President Harry S. Truman appointed Dr. Breslow director of a commission to assess the nation’s health care. The panel’s report emphasized that people make their own health choices but “exercise them mainly under social influences.”

    In 1969, as president of the American Public Health Association, he said the public health profession must go beyond issuing scientific reports and suggest social actions to improve people’s lives. “In the long run, housing may be more important than hospitals to health,” he said.

    He advised a half-dozen presidential administrations and was director of the California Public Health Department in the mid-1960s. Gov. Ronald Reagan fired him in 1967, citing “philosophical differences” over state cuts in medical care for the poor.

    As an official of the California department in the 1940s and ’50s, he did some of the early definitive studies on the harmful effects of smoking. Three of these studies were cited in the United States surgeon general’s landmark report in 1964 linking cigarettes to lung diseases, particularly cancer.

    But it was the Alameda County study that rocked the public health world, because it proved with numbers that behavior indisputably affected longevity. Its recommendations: do not smoke; drink in moderation; sleep seven to eight hours; exercise at least moderately; eat regular meals; maintain a moderate weight; eat breakfast.

    A follow-up study showed that those who followed better habits were less likely to become disabled. Of those with four or more good health habits, 12.2 percent were likely to be disabled 10 years after the study began; those with two or three, 14.1 percent; and those with only one or no positive health habits at all, 18.7 percent.

    Dr. Breslow found that a 60-year-old who followed the seven recommended behaviors would be as healthy as a 30-year-old who followed fewer than three.

    Lester Breslow was born March 17, 1915, in Bismarck, N.D., where his parents had moved to escape the teeming poverty of the Lower East Side of Manhattan. His father, a pharmacist, opened a drugstore in Bismarck. Lester devoured socialist books and newspapers as a teenager, he wrote in his autobiography, “A Life in Public Health: An Insider’s Retrospective” (2004). He overcame a stutter to speak at his high school graduation.

    He graduated from the University of Minnesota Medical School in 1938 with the intention of being a psychiatrist, but he soured on the field while working at a psychiatric hospital in the summer because he doubted much could be done to help the patients.

    He shifted to public health, he said, because he thought it suited his ideology as “a political activist for disadvantaged people.” After a public health internship at a hospital in Staten Island, he applied to the United States Public Health Service Corps but was rejected — “I assume because of my political orientation,” he wrote.

    Dr. Breslow returned to the University of Minnesota and earned a master’s in public health in 1941. He joined the Minnesota Department of Public Health as an epidemiologist, handling six rural counties.

    In 1943 he joined the Army, even though his job and having a young child both exempted him from the World War II draft. He wrote that he felt guilty because he had not earlier joined the “antifascist struggle” by volunteering to fight in the Spanish Civil War. He served in the Pacific as a captain.

    After his discharge, he approached the California health department about a job, making the case that it needed a chronic-disease specialist. The director told him to go back to Minnesota, but a subordinate quietly brought him on board.

    After 21 years at the agency, Dr. Breslow was hired by U.C.L.A. as dean of the public health school, a post he held for eight years. He wrote more than 200 scientific publications, and was founding editor of The Annual Review of Public Health and The Encyclopedia of Public Health. In addition to serving as president of the public health association, he was president of the International Epidemiological Association and the Association of Schools of Public Health.

    Dr. Breslow’s first marriage ended in divorce. He is survived by his wife, the former Devra J. R. Miller; three sons from his first marriage, Norman, Jack and Stephen; three grandchildren; and four great-grandchildren.

    In 2010, Dr. Breslow, then 95, joined with Prof. James E. Enstrom of U.C.L.A. to publish a paper about a group of California Mormons whom they had studied over 25 years. The life expectancy of the Mormon males was 9.8 years greater than that of the general population of white American males; female Mormons lived 5.6 years longer than their general-population counterparts. The authors credited the Mormons’ healthy lifestyle.

    Dr. Breslow himself did not smoke or drink. He walked regularly, practiced moderation in all things and enjoyed tending his vegetable garden.
     
  17. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Heyn H, Li N, Ferreira HJ, et al. Distinct DNA methylomes of newborns and centenarians. Proceedings of the National Academy of Sciences. http://www.pnas.org/content/early/2012/06/05/1120658109.full.pdf

    Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine—phosphate—guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level.
     
  18. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Honda Y, Higashibata A, Matsunaga Y, et al. Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans. Sci Rep 2012;2. Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans : Scientific Reports : Nature Publishing Group

    How microgravitational space environments affect aging is not well understood. We observed that, in Caenorhabditis elegans, spaceflight suppressed the formation of transgenically expressed polyglutamine aggregates, which normally accumulate with increasing age. Moreover, the inactivation of each of seven genes that were down-regulated in space extended lifespan on the ground. These genes encode proteins that are likely related to neuronal or endocrine signaling: acetylcholine receptor, acetylcholine transporter, choline acetyltransferase, rhodopsin-like receptor, glutamate-gated chloride channel, shaker family of potassium channel, and insulin-like peptide. Most of them mediated lifespan control through the key longevity-regulating transcription factors DAF-16 or SKN-1 or through dietary-restriction signaling, singly or in combination. These results suggest that aging in C. elegans is slowed through neuronal and endocrine response to space environmental cues.