SuperAgers Initiative – discovering the science behind exceptional longevity

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

SuperAgers are individuals aged 95 and older; they are a promising, living source of scientific knowledge who can provide real-time insights into healthy longevity and what it means to age healthily.

The experience and biology of SuperAgers can open an unique window on aging, offering insights into how we can understand, measure and leverage the correlation between age-related diseases and living an exceptionally long, healthy life.

Longevity.Technology: By studying individuals age 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 extend years of health. It’s an exciting project, and we sat down with Dr Nir Barzilai, AFAR Scientific Director and Director of the Einstein-Institute for Aging Research, to find out more.

The motivation behind the project was trying to answer the question “How do we get science to help us design drugs?”

“We have people who live to 100, and it’s not only living longer, it’s that they are also healthier – maybe 30 extra years of health,” says Barzilai. “Not only are they healthier for longer, but they experience a contract of morbidity – sick for less time at the end of their lives.”

Barzilai explains that what pharmaceutical companies want when it comes to diseases – whether that’s diabetes, cardiovascular, cholesterol-related or whatever – is more information on human genetics.

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

Barzilai gives the example of cholesterol drug PCSK9 inhibitor which came about not through animal studies, 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 – understanding how led to drugs that inhibit PCSK9 and prevent the degradation of cholesterol receptors.

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

“We found a lot of data with 750 centenarians, but we need ten-fold that number to validate our findings,” says Barzilai. “We’re aiming for 10,000 SuperAgers, 10,000 of their offspring who are likely to live long – and we can come back for more information as time goes on. Maybe the offspring get married and their spouses act as the control if they don’t have longevity in their family. It’s living data, increasing and evolving. And it’s a more diverse population.”

The American Federation of Aging Research is going to launch a community website to gather as much information as possible, encouraging registrations from SuperAgers and their relatives. Those willing to participate will be sent a swab kit so their genetics can be added to the data bank and the data will be made available for everyone as soon as possible.

“Previous research has looked at one change in our DNA across thousands of people, or event tens of thousands, to see if it is associated with diabetes, for example,” explains Barzilai. “But we are not built from one change at a time – there are lots of changes.”

Current research is now putting every change into a pathway which is allowing Barzilai and the other researchers to look at effects both downstream and upstream.

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

“But what is rather incredible is that almost 60% of our centenarians have something that prevents the action of growth hormones – it makes sense, as we see from nature that smaller dogs, for examples, live longer than larger breeds and also because bodies need to shift from growth to repair.”

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

Instead, says Barzilai, researchers are looking through the data for diseases that are accelerated by aging, but it’s an obstacle.

“The proof of concept is there and the preclinical data is there – we can get extension of lifespan and healthspan in animals, we just don’t have enough data to develop it for aging – yet.”

It all comes down to targets, says Barzilai.

“Now we are identifying targets we can actually wrap our hands around,” he explains. “To reverse aging – the Fountain of Youth – to take an old person and make them young would be very, very difficult. To be Peter Pan – to be young forever – needs interventions that modulate your epigenetics… so maybe in fifty years from now. But for now, there are many targets that are metabolic targets, and the more data we have, the better.”

Find out more about the AFAR’s SuperAgers Initiative HERE.

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