Are There Secrets to Old Age

Scientists Probe Longevity

A wife is essential to great longevity; she is the receptacle of half a man's cares, and two-thirds of his ill-humour.

- Charles Reade

Washington - You've heard of the type: they eat whatever they want and maybe they smoke. Some of them exercise, some don't. And they live to be 100. What's their secret? Is it good genes, good habits - or just good luck? It's a question that researchers are trying to answer.

"We have 100-year-olds who have smoked all their lives; we have 100-year-olds who are fat," said Dr Nir Barzilai, a Yeshiva University researcher seeking longevity genes.

"This is a ripe time to begin looking at this extraordinary group," said Dr Robert Butler, director of the International Longevity Centre, a New York City centre where researchers look at how societies react to ageing. Just one in 10,000 Americans has lived a century. They're the fastest growing age group, and by 2050 - when the oldest baby boomers would reach 100 - there could be nearly a million people that age or older, the Census Bureau says. An exact number is expected in June.

Scientists record what the centenarians eat, what they don't and how they've handled stress. Children, siblings and spouses are also part of the research. So far, centenarians have shattered myths, and raised more questions about extreme old age.

Researchers know for certain that few 100-year-olds have had heart attacks, developed Alzheimer's or been hit by diabetes. "We're constantly disproving the idea of the older you get, the sicker you get," said Dr Thomas Perls, director of the New England Centenarian Study at Harvard Medical School. "They are avoiding or delaying these diseases. We've got to find out how and why they do that."

Researchers know that generally, the siblings of centenarians tend to live long themselves; siblings of centenarians are at least four times more likely than the greater population to reach their 90s, and are eight times as likely to get to 100. So far, genes that extend life have only been identified among insects. When the right human genes are discovered, researchers insist, the goal will not be to create an elixir to prevent ageing. The point will be to help everyone live healthier lives by developing treatments for the diseases that kill people well before they reach 100.

There are discoveries researchers haven't explained. Centenarian women outnumber men, but are sicker and more frail. Women who have a child after 40 are 5 times as likely to reach the century mark than other women.

Centenarians are all races. The only thing researchers have found they share is that many had a family member who lived long as well. Some research is showing that genes don't hold all the keys. Perls, a 40-year-old doctor who has studied centenarians for the last 7 years, said centenarians score lower on a psychological test for neurotic conditions or traits. In other words, they don't dwell on things. - AP

Source: The Evening Post Thursday 3 May 2001

Gene Tied to Longevity also Preserves Ability to Think Clearly

A man 90 years old was asked to what he attributed his longevity.
"I reckon," he said with a twinkle in his eye, "it's because most nights I went to bed and slept when I should have sat up and worried."

- Garson Kanin

Bronx, New York - A gene variant linked to living a very long life - to 90 and beyond - also serves to help very old people think clearly and retain their memories, according to new research by scientists at the Albert Einstein College of Medicine of Yeshiva University. Their findings are published in the 26 December 2006 issue of Neurology. Led by Dr Nir Barzilai, director of the Institute for Aging Research at Einstein, the researchers examined 158 people of Ashkenazi (Eastern European) Jewish descent who were 95 or older. Compared with elderly subjects lacking the gene variant, those who possessed it were twice as likely to have good brain function based on a standard test of cognitive function.

Later the researchers validated their findings independently in a younger group of 124 Ashkenazi Jews between the ages of 75 and 85 who were enrolled in the Einstein Aging Study led by Dr Richard Lipton. Within this group, those who did not develop dementia at follow up were 5 times more likely to have the favourable genotype than those who developed dementia.

Dr Barzilai and his colleagues had previously shown that this gene variant helps people live exceptionally long lives and apparently can be passed from one generation to the next. Known as CETP VV, the gene variant alters the cholesterol ester protein. This protein affects the size of "good" HDL and "bad" LDL cholesterol, which are packaged into lipoprotein particles. Centenarians were 3 times likelier to possess CETP VV compared with a control group representative of the general population and also had significantly larger HDL and LDL lipoproteins than people in the control group. Researchers believe that larger cholesterol particles are less likely to lodge themselves in blood vessels. So people with the CETP VV gene (and the larger cholesterol particles they produce) run a lower risk of heart attacks and strokes, which may explain their unusual longevity.

The findings of this new study suggest that CETP VV also protects the cognitive integrity of the brain - either through the same vascular "anti-clogging" benefit that prevents heart attacks and strokes or through an independent protective mechanism that remains to be found. "Without good brain function, living to age 100 is not an attractive proposition," says Dr Barzilai. "We've shown that the same gene variant that helps people live to exceptional ages has the added benefit of helping them think clearly for most of their long lives. It's possible that CETP VV's cognitive effect is to protect against the development of Alzheimer's disease. In studying these centenarians, we hope to learn why they're able to resist diseases that affect the general population at a much younger age. This knowledge should greatly aid our efforts to prevent or delay the onset of age-related diseases."

Other Einstein scientists involved in the study were Dr Gil Atzmon, Dr Carol Derby, Dr Jonathan Bauman and Dr Richard Lipton. The study was supported by grants from the Einstein Aging Study, the Paul Beeson Physician Faculty Scholar in Aging Award, the Ellison Medical Foundation Senior Scholar Award, the National Institutes of Health, the Albert Einstein College of Medicine, and the Baltimore VA Geriatric Research and Education Clinical Center.

Source: eurekalert.org 25 December 2006

Three "Longevity Factors" Found in Monkeys and Men

One could look over the past century and ask oneself, has the increased longevity been good, bad or indifferent?

- Leon Kass

New York - Men who have three "longevity factors" seen in animals on calorie-restricted diets appear to enjoy a longer life span - even without cutting back on calories. The factors

a low body temperature

low blood levels of insulin, and

slower decline in the hormone DHEAS

were found in rhesus monkeys fed a diet with 30% fewer calories than normal.

Although most of the animals are still living, it seems that the restricted-calorie diet is boosting the monkey's life span, according to the report issued Thursday in the journal Science. The mortality rate is about 15% in the calorie-restricted monkeys compared with 24% in monkeys allowed to eat as much food as they want. Many studies in rats and other animals have suggested that fewer calories equal a longer life, and the three factors have been seen in those species on a reduced-calorie diet. However, it has not been clear if the three factors are important in monkeys and/or humans, according to the researchers from the National Institute on Ageing, a division of the National Institutes of Health in Baltimore, Maryland.

In the new study, Dr George S Roth and colleagues looked at these factors in the rhesus monkeys, as well as 700 men enrolled in the Baltimore Longitudinal Study of Ageing. The men were split into two groups - those with higher body temperature and insulin levels and low levels of DHEAS, and a group with lower body temperature, insulin levels and higher DHEAS. The men reported consuming about 2,300 calories a day and were not necessarily on a calorie-restricted diet.

Men with lower levels of insulin, lower body temperature and higher levels of DHEAS tended to live longer, as did the calorie-restricted monkeys that showed a similar trend in those three factors. "The fact that these men apparently weren't practicing caloric restriction is important because it means that there may be other ways to achieve biological hallmarks without having to undergo drastic dietary changes," Roth said in a statement issued by the NIH. "Although we don't yet know what these pathways are, this finding suggests it may be possible to develop compounds that offer the benefits of caloric restriction without having to resort to it," he added.

While it is not clear exactly what environmental or genetic factors cause the men to have factors that mimic calorie restriction, it appears that those factors are related to longevity and are "therefore worthy of further investigation," the authors conclude.

Taken from an article in the weekly magazine Science 2002;297:811

Source: Reuters 1 August 2002

Stem Cell Activity Deciphered in the Ageing Brain

The great increase in longevity has produced a surge in the desire to accumulate assets for retirement.
It has outpaced the ability of the private sector to produce assets, so we need a larger government debt.

- William Vickrey

Durham, North Carolina - Neurobiologists have discovered why the ageing brain produces progressively fewer new nerve cells in its learning and memory centre. The scientists said the finding, made in rodents, refutes current ideas on how long crucial "progenitor" stem cells persist in the ageing brain. The finding also suggests the possibility of treating various neurodegenerative disorders, including Alzheimer's disease, dementia and depression, by stimulating the brain's ability to produce new nerve cells, said senior study investigator Ashok K Shetty, Phd, professor of neurosurgery at Duke University Medical Center and medical research scientist at Durham VA Medical Center.

Results of the study appear online in the journal Neurobiology of Aging. The research was funded by the National Institutes of Health and the US Department of Veterans Affairs.

Previous studies by Shetty and others had demonstrated that as the brain ages, fewer new nerve cells, or neurons, are born in the hippocampus, the brain's learning and memory centre. In one study, Shetty and colleagues showed that the production of new neurons in rats slows down dramatically by middle age - the equivalent of 50 years in humans. But scientists did not know what causes this decline. The common assumption had been that the brain drain was due to a decreasing supply of neural stem cells in the aging hippocampus, said lead study investigator Bharathi Hattiangady, Phd, research associate in neurosurgery. Neural stem cells are immature cells that have the ability to give rise to all types of nerve cells in the brain.

In the current study, however, the researchers found that the stem cells in ageing brains are not reduced in number, but instead they divide less frequently, resulting in dramatic reductions in the addition of new neurons in the hippocampus.

To conduct their census, the researchers attached easy-to-spot fluorescent tags to the neuronal stem cells in the hippocampus in young, middle-aged and old rats. They found that in young rats, the hippocampus contained 50,000 stem cells - and, significantly, this number did not diminish with ageing. This finding, the researchers said, suggested that the decreased production of new neurons in the aged brain was not due to a lack of starting material.

The researchers then used another fluorescent molecule to tag all stem cells that were undergoing division in the process of staying "fresh" in case they were recruited to become mature nerve cells. They found that in young rats, approximately 25% of the neural stem cells were actively dividing, but only 8% of the cells in middle-aged rats and 4% in old rats were dividing. This decreased division of stem cells is what causes the decreased neurogenesis, or birth of nerve cells, seen with ageing, the scientists said. "This discovery provides a new avenue to pursue in trying to combat the cognitive decline associated with conditions such as Alzheimer's disease and with ageing in general," Hattiangady said.

The team now is searching for ways to stimulate the brain to replace its own cells in order to improve learning and memory function in the elderly. One approach being explored is to treat older rats with drugs designed to mimic the action of compounds called neurogenic factors, which encourage stem cells in the brain to divide, Shetty said. The researchers also are grafting neural stem cells grown in culture dishes into the hippocampus, to stimulate those already present. Additional approaches include using behavioural modification techniques, such as physical exercise and exposure to an enriching environment, that are known to stimulate proliferation of stem cells.

Media contact: Marla Vacek Broadfoot marla.broadfoot@duke.edu

Source: dukemednews.org 18 December 2006