Dorian Gray, Wolverine and Peter Pan – ahead of the Longevity Leaders Congress, Dr Nir Barzilai talks longevity labels and tackling aging.
Dr Nir Barzilai, Director of The Institute of Aging Research at the Albert Einstein College of Medicine, is a key player in the longevity space. With a keen interest in the biology of tackling aging, he is looking at the genetics of exceptional longevity, exploring the hypothesis that centenarians have protective genes, which allow the delay of aging or for the protection against age-related diseases.
Barzilai is also the driving force behind the Targeting Aging with Metformin (TAME) trial, which aims to create a template for trials of age targeting therapies. It is no surprise, then, that Barzilai will feature prominently at the Longevity Leaders World Congress next week, the definitive global meeting with the mission of extending human lifespan and healthspan and delivering healthy aging.
Longevity.Technology: Regenerative medicine is going from strength to strength, with over 50 regenerative medicine advanced therapy (RMAT) designations in the US to date. Barzilai is a member of a Keynote Panel at the Congress considering the question Regenerative, Rejuvenate or Reprogram?, so we asked him to elucidate when we sat down with him recently.
Barzilai makes the same point as James Peyer – when we consider these longevity therapy avenues it’s a case of and, not or.
“We have three scenarios,” Barzilai explains. “The first is the Dorian Gray scenario, who appeared to never age, but a hidden portrait revealed the truth. So for us, that equates to targeting aging so we can delay it. The second is the Wolverine scenario, or Fountain of Youth, where – to simplify – put an old person in a special rejuvenating bath, and they get out younger. This is the most difficult task that we have – we can improve health in older people, but we cannot make them young or live longer.
“The third scenario is Peter Pan, who, of course, did not age. The idea would be that when you’re 20 or 30, you would undergo treatment that would reprogram you – erase the aging and will allow you not to age.”
All of these scenarios are worth considering, says Barzilai, with the most important scenario being Peter Pran – although this is also the farthest out, research-wise. “The rejuvenation of old to young is really difficult, but that doesn’t mean we shouldn’t want to try it – it’s tricky,” Barzilai says.
Ascribing labels can be a fraught business and the language of longevity can also inform its debate, whether we are discussing aging, anti aging, increased healthspan, healthy aging or comorbidities. Previously Barzilai has encouraged research to look beyond the language, saying that it doesn’t really matter what we call aging, so long as work happens to slow it down.
“That was part of my effort to encourage the FDA to recognise aging as a target,” Barzilai explains. “None of us want to call aging a disease – aging is the mother of the disease. It’s not a biological perspective, but about getting treatment. Rather than calling aging a disease, we’re going to delay age related diseases. So you can call it whatever you want – we’ll call it aging.”
Barzilai describes this as partly a marketing issue. “When I started my career, the term aging meant frailty, sickness and death to most people,” he explains. “Longevity just meant living longer with disease. There was no association between enhancing lifespan and healthspan, but my research on centenarians showed that enhanced healthspan generally associates with enhanced lifespan. My centenarians were healthier for longer, they lived longer, they had contracted morbidity.”
When it comes to choosing words, the key one for Barzilai is geroscience. “We are geroscientists, a professional name; we want to discover geroprotectors and gerotherapeutics. This is important because the field of antiaging is a home to charlatans and people who promise all sorts – take this, live forever, and if you don’t, no-one is going to sue us.
“But our industry is a science based industry – our goal is healthspan and lifespan. Let’s put them together. It’s the same mechanism, so if we target aging, we’ll get both. I’m not anti anything – I’m pro healthier people.”
Dr Barzilai is also presenting on TAME at the Congress, and we asked him how the metformin trial was going.
“I’m not curious about the results,” he says. “I’m pretty sure about the results and the reason is because there is preliminary data. Some really good clinical studies were done to show that metformin prevents diabetes versus placebo, that it prevents cardiovascular disease, that it works in non-diabetics, that it decreases mortality, that it decreases cancer, so I’m not curious about that. The reason we’re doing this study is only to get an FDA approval for this concept, that there are drugs that will move a cluster of disease and delay them or prevent them altogether – this is the reason.
Metformin is a tool, says Barzilai. It’s a good tool, but it’s just a tool – it’s generic, so there is no pharmaceutical push, the researchers are geroscientists and the funding from is the American Federation of Aging Research, so it’s significant.
“Let’s take out all the noise and focus about how we achieve the goal that the FDA will see aging can be tackled,” says Barzilai. In addition, he says, TAME could also set the template for other companies to develop better drugs and better combinations of drugs and get to this point themselves.
“But there is another very important purpose for TAME,” says Barzilai. “There are biomarkers for biological aging, but we are desperate to have biomarkers that will change in several weeks or months, like we can measure cholesterol, right. That will help the industry to really find out what’s really working in a very short time, rather than undertaking a Phase III trial for every drug that we have. So TAME has the potential to get the biomarkers for aging and open up for the industry, not only the indications, but also the way to get there.”