Six of the eight Hurlburt siblings live in New England, including Peggy (79), Helen (88), Millie (93), Peter (80), Agnes (96) and Muriel (89)
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The challenge for researchers is to identify those genes that contribute not just to longevity but to healthy longevity in particular. Based on its unique collection of genetic data from the New England Centenarian Study, Perls' team is close to identifying such a suite of genes. From the evidence gathered so far, it appears that for the most part, people who live to 100 and beyond do not necessarily avoid the chronic diseases of aging that normally claim the rest of us after midlife. About 40% of centenarians have experienced one of these illnesses in their lifetimes, but they seem to push through them without long-term problems or complications. And when they do get sick, according to a study Perls conducted in 1996, they are less likely to log time in the intensive-care unit (ICU) and often require less-expensive care per admission — at least compared with the cardiac surgery, chemotherapy and other ICU procedures that many of their younger elderly counterparts need.
Even as the LLFS investigators look for the full sweep of genes behind such resilience, other researchers are focusing on individual areas of the body — particularly the brain. Dr. Bruce Yankner at Harvard Medical School is studying what distinguishes brains that make it to 100 with limited cognitive decline from those that succumb to the ravages of Alzheimer's disease or other forms of dementia before age 85. Yankner zeroed in on genes in the frontal cortex — which is involved in higher learning, planning and goal setting — of people ages 24 to 106. That's a big chronological span, and it netted a big genetic haul: the research identified no fewer than 440 genes that start to slow down after age 40. Using that set as a starting point, Yankner's group is trying to determine just what those genes do to affect individual aging processes.
The virtue of such an approach is that it gives you a look at the entire developmental trajectory of the key genes throughout the adult life span. The disadvantage is that it lacks specificity: you can't ever know which 24-to-80-year-olds will actually make it to 90 and beyond, so you can't be certain from looking at their brains which genes are really at work in extreme old age and which eventually deteriorate. For that reason, Yankner's team — like the LLFS investigators — is also studying the brains of a separate group of people who have already achieved extreme old age. Coming at the data from two different directions could better pinpoint the genes that are truly in play and lead to a reasonable library of targets for deeper research.
"It's a work in progress, but we believe that the expression of genes in the brain and how they are regulated is at least an indicator of how well someone is aging," Yankner says. "It may play a causal role as well."
Indeed, a causal role is precisely what the early results suggest. The key function of the collection of brain genes Yankner has identified is to regulate the connections between neurons — vitally important, since it's healthy connections that keep neurons alive. Among the first ones to go when brain cells start dying are those involved in learning and memory. This may help explain why even the sharpest oldsters are prone to so-called senior moments, a tendency to forget newly learned information or repeat stories or questions, sometimes over and over again. Other genes in the collection have more-precise repair duties, fixing small nicks and mistakes in DNA. Without such maintenance work, normal genetic activities are slowly compromised.
Yet despite his excitement over his genetic findings, Yankner too is adamant that DNA is not destiny. Just as you can keep your body fit with good lifestyle habits and by avoiding pollutants, toxins and carcinogens, you may be able to keep your genes healthier. Environmentally triggered alterations in genes — known as epigenetic changes — can affect when a gene is activated, how robustly it is turned on and how it interacts with neighboring genes. Free radicals provide a very good case study of how epigenetic processes play out.