“In our studies, we’re not so interested
in specific diseases,” said Barzilai. “We’re
interested in aging. If something targets aging,
we expect it to counter several diseases and
Barzilai and his research team recently conducted the Longevity Genes Project, studying more than 600 healthy seniors, healthy at 95, and their children. They discovered that these centenarians lived longer, healthier lives at the end of their lifespan and their disease period was shortened. And although the first 44 centenarians in the study to have their whole genomes sequenced had pathogenic variants, including degenerative mutations, none of them had those diseases.
Interestingly, when considering the age of disease onset, centenarians who did get a particular disease contracted that disease 20-30 years later than the control population. Said Barzilai, “What the centenarians have shown us is that the longer you live, the healthier you stayed.”
An unexpected twist in one study was a finding that obesity, longtime smoking and a lack of moderate physical activity mattered for some, but for many these factors didn’t affect their longevity. Barzilai doesn’t claim that healthy lifestyle choices don’t matter. Instead, he posited that some of these people with their longtime vices just have an exceptional genome or perhaps they have protective alleles to assure their longevity.
In a talk titled “How to Die Young at a Very Old Age,” Barzilai, an NIA grantee who is also director of NIH’s Nathan Shock Centers of Excellence in the Basic Biology of Aging, emphasized the need not only to treat disease, but also to target aging.
Photos: Ernie Branson
Barzilai’s studies also revealed that the children of centenarians had less diabetes, stroke, hypertension and myocardial infarction than their parents. A recent NIDDK diabetes prevention clinical trial had a similar finding—that people whose father or mother lived to be older than 80 had a third less chance of getting diabetes. “The offspring of longer-lived parents had lower diabetes rates and it was independent of the parent’s diabetes or their treatment,” he said.
This research, and the potential to identify longevity genes, may pave the way for new drug therapies to help people live longer and prevent, or considerably delay, age-related diseases.
The drug metformin, often prescribed to treat type 2 diabetes, may interact with hormones, insulin, inflammatory and other pathways that improve health span and longevity, said Barzilai. The drug has shown age-delaying effects in mice. Metformin also delayed diabetes onset in people in a recent NIDDK study and delayed cardiovascular disease by 30 percent in a recent U.K. study. Early research also suggests metformin may delay cognitive decline even in non-diabetic patients.
Preliminary studies also show promising results for low growth hormone IGF-1 action in its effect on longevity, said Barzilai. This hormone may be linked to an increased risk of some forms of cancer, though it has been shown to have protective qualities against heart disease, osteoporosis and diabetes. Barzilai said current studies are testing whether keeping IGF-1 high in the brain but low in the rest of the body may reduce cancer risk while extending human survival rates.
Despite the data, Barzilai said it’s difficult to acquire medicines that specifically target aging, in part because the Food and Drug Administration does not yet recognize aging as a disease. In the meantime, his lab continues to uncover the influences that promote resistance to the effects of aging. Genetic, environmental and medicinal interventions have proven to delay aging in many species, from mice to primates. Barzilai hopes to develop interventions with the goal of helping more humans live longer, healthier lives.