SuperAgers – discovering the science behind exceptional longevity

SuperAgers research is based on learning from people who live long – how can it help us improve our health and longevity?

SuperAgers are people aged 95 and over; They are a promising, living source of scientific knowledge that can provide real-time insights into healthy longevity and what it means to age healthily.

The experience and biology of SuperAgers may open a unique window on aging and offer insights into how we can understand, measure, and exploit the correlation between age-related diseases and exceptionally long, healthy lives.

Longevity.Technology: By studying individuals 95 and older, the American Federation for Aging Research’s SuperAgers initiative builds on a foundation of research into the biology of aging and promising therapeutics to prolong health. It’s an exciting project and we’ve teamed up with Dr. Nir Barzilai, Scientific Director of AFAR and Director of the Einstein Institute on Aging, sat down to learn more.

The motivation behind the project was to try to answer the question: “How can we get science to help us develop drugs?”

“We have people who live to be 100, and not only are they living longer, they’re also healthier — maybe 30 extra years of health,” Barzilai says. “Not only are they healthier for longer, but they also experience a morbidity contract — they end up sick for less time.”

Barzilai explains what pharmaceutical companies want when it comes to diseases—whether it’s diabetes, cardiovascular disease, cholesterol or whatever—is more information about human genetics.

“We fail if we assume that something that works in mice can inevitably be developed for humans,” he says. “The more human genes we can sequence, the better we can understand and fight diseases.”

Barzilai cites the example of the cholesterol drug PCSK9 inhibitor, which came about not through animal testing but because researchers identified mutations in the PCSK9 gene, which provides instructions for making a protein that helps regulate the amount of cholesterol in the bloodstream. The mutations disrupt the function of PCSK9 and cause hypercholesterolemia – the understanding led to drugs that inhibit PCSK9 and prevent the breakdown of cholesterol receptors.

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“Pharmaceuticals are looking for genetic evidence that drugs work in humans, and this sparked the Longevity Genes Study, examining centenarians,” explains Barzilai. “But for validation purposes we need more people! By recruiting more SuperAgers and their families, and looking at longevity genes, we can design better drugs to slow aging.”

“We found a lot of data with 750 centenarians, but we need 10 times that number to validate our results,” says Barzilai. “We’re aiming for 10,000 SuperAgers, 10,000 of their offspring who are likely to live long lives – and we may come back for more information over time.” Perhaps the offspring marry and their spouses serve as controls if they do not have longevity in their family. It is living data, growing and evolving. And it’s a more diverse population.”

The American Federation of Aging Research will launch a community website to gather as much information as possible and encourage registrations from SuperAgers and their families. Those willing to participate will be given a swab kit so their genetics can be added to the database and the data made available to everyone as soon as possible.

“Previous research has looked at a change in our DNA in thousands or even tens of thousands of people to see if it’s linked to diabetes, for example,” explains Barzilai. “But we’re not building on one change at a time — there’s a lot of change.”

The current research now puts each change in a pathway that allows Barzilai and the other researchers to study the impacts both downstream and upstream.

“If we look at the signaling pathways of our SuperAgers, we see that the signaling pathways are the same as predicted from animal studies — mTOR, insulin, IGF signaling — which is reassuring,” he says.

“But what’s quite incredible is that almost 60% of our centenarians have something that prevents growth hormone from working – it makes sense since we see from nature, for example, smaller dogs live longer than larger breeds and also because bodies need to transition from growth to repair.”

Barzilai points to the development of cancer drugs that act on the IGF1 receptor. “When we gave this drug to old animals, they lived healthier lives, they had better lives. But while aging is not recognized as a disease, we cannot develop these drugs ‘for aging’.”

Instead, Barzilai says, researchers are sifting through the data for diseases that are accelerated by aging, but that’s a stumbling block.

“The proof of concept is there and the preclinical data is there — we can achieve lifespan and health extension in animals, we just don’t have enough data to design it for aging — yet.”

It’s all about goals, says Barzilai.

“Now we’re identifying goals that we can actually take care of,” he explains. “Reversing aging – the fountain of youth – taking an old person and making them young would be very, very difficult. Being Peter Pan—being young forever—needs interventions that modulate your epigenetics… so maybe in fifty years. But right now there are a lot of targets that are metabolic targets and the more data we have the better.”

Learn more about AFAR’s SuperAgers Initiative HERE.

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