Scientists Clash Over Longevity --- Antiaging movement has raced ahead amid fierce debates over its theories

"Leonard Guarente was 38 and already a tenured professor at Massachusetts Institute of Technology when he decided to devote himself to one of the most alluring problems in biology: how to slow down aging.

More than three decades later, the 72-year-old Guarente is considered a grandfather of the booming longevity movement. Top science journals have published his discoveries about genes. He is an architect of one of the field's biggest ideas, has trained its most influential scientists and helped create the company behind a suite of popular supplements.

Now the field he shaped has moved from the fringes to science's hot center. It's drawn billions in investment in recent years, and is poised to draw even more attention under the Trump administration. Even so, the science behind longevity remains fiercely debated by those in the field, many of whom are building businesses based on still-emerging research -- and Guarente is at the forefront there, too.

Critics of his theories include former proteges and rival scientists. Many sell or promote their own supplements or champion other purported antiaging treatments in the murky longevity market.

Ads for various products sometimes tout clinical evidence, but studies are generally small, preliminary and conducted over short periods -- and there's no proof that taking them over the long term is safe. Consumers can't be sure where the science ends and the marketing begins.

Guarente has argued that a family of genes called sirtuins control aging, and the molecules that help them do their job decline as people age. Maintaining youthful levels of those molecules will keep sirtuins active longer and slow down aging, Guarente contends.

Elysium Health, the company he co-founded in 2014, sells longevity supplements for $40 to $60 a bottle that he says activate sirtuins.

Guarente said the seven Nobel laureates on Elysium's board demonstrate the seriousness of its work. Studies by Elysium, Guarente's MIT lab and other respected scientists prove that sirtuins influence longevity, he said.

When Matt Kaeberlein was a Ph.D. student in Guarente's lab in the 1990s, he demonstrated that a sirtuin gene in yeast extended longevity. He's since moved on. He co-authored a paper published in 2011 questioning whether sirtuins affected the lifespans of worms and flies. And despite hundreds of millions of dollars in National Institutes of Health and private funding spent over the past two decades examining sirtuins, he said, there is still no strong evidence they are important players in aging.

"I don't think anyone can say with a straight face, we have rock solid data, we have clinical trial data, showing these things work for the people buying them," said Kaeberlein, who is now the CEO of Optispan, a healthcare technology company, and co-director of an NIH-funded trial testing whether the drug rapamycin, used to prevent organ rejection in transplant patients, extends lifespan in dogs.

"In the aging field, people have their favorite theory. It drives a lot of critique of theories that are not yours," Guarente said.

It isn't uncommon for former proteges and rivals to question another scientist's signature discovery in cutting-edge science. But the stakes for longevity are growing as the movement gains prominence.

Robert F. Kennedy Jr., now secretary of the Department of Health and Human Services, has said he follows an antiaging protocol. Proposed Health and Human Services deputy Jim O'Neill is the former chief executive at a nonprofit that funds longevity research.

Some of the scientists driving the movement are pushing for changes in funding and regulations to speed up the development of antiaging interventions. The longevity industry attracted $55.7 billion in global investment over the past decade, according to research and media company Longevity.Technology.

Guarente said some of sirtuins' detractors have ignored promising evidence because they back other interventions or don't believe scientists will succeed in slowing aging. "It's a question of whether you look at the status of a field and you focus on it being half-empty or the glass being half-full," he said.

Guarente grew up in the working-class beach town of Revere, Mass. He earned a bachelor's degree in biology at MIT, did his Ph.D. and postdoc work at Harvard and returned to MIT in 1981. He started studying how genes get turned on and off in cells. After he got tenure at age 34, he said, he wanted to switch his area of research to a subject where he might solve a major scientific problem.

In 1990, two graduate students interviewing for jobs at his lab told him they wanted to search for genes that might point to clues about aging. Biologists often start studies in yeast, which are easy to grow in the lab. After the students showed promising results, Guarente was hooked. Eventually, his entire lab was studying aging.

His lab found that without sirtuins, cells age more quickly -- and sirtuins require a molecule called nicotinamide adenine dinucleotide, or NAD, to do many crucial jobs, such as repairing DNA and making energy. Many, but not all, scientists believe NAD levels decline as we age.

Guarente built Elysium on the idea that boosting NAD levels to youthful levels can keep sirtuins active, in turn slowing aging and extending life.

From early on, Guarente pursued longevity as both science and business. In 1999, he co-founded Elixir Pharmaceuticals, which shut down before it could get an antiaging drug to market.

In 2007 he became co-chair of the scientific advisory board of Sirtris Pharmaceuticals, co-founded by his former protege David Sinclair. Sinclair -- who is now one of the most well-known, and controversial, names in the field -- trained in Guarente's lab from 1995 to 1999 then moved to Harvard, where he advanced the idea that activating sirtuins has health benefits.

Sirtris was developing a formulation of resveratrol, a compound found in red wine that showed promise in extending the lifespan of worms and mice on a high-calorie diet. Pharmaceutical giant GSK acquired Sirtris in 2008 for $720 million. GSK stopped a study testing the drug in cancer patients in 2010 over safety concerns, and said in 2013 it would close Sirtris. Guarente continued to consult for GSK on sirtuins for another year or two.

In 2012, Guarente got a call from Eric Marcotulli, a partner at Sequoia Capital who as a Harvard Business School student had been assigned a case study about Sirtris. Marcotulli's professor asked the students to think about the options Sirtris was considering, including selling a version of resveratrol directly to consumers as a supplement or cutting a deal with a pharmaceutical company.

Marcotulli, a former college wrestler who had taken fish oil, vitamin D and other supplements over the years, said he was one of the few arguing Sirtris should sell resveratrol as a supplement.

Marcotulli was interested in trying to find natural compounds that could slow aging. Both Marcotulli and Guarente said they wanted to do rigorous tests to bolster consumer trust. After more conversations, Marcotulli asked Guarente which of all the compounds looked the most promising.

"I would put my bets on NAD boosters," Guarente said.

They co-founded Elysium in 2014, along with another partner. Elysium's first product, called Basis, combined nicotinamide riboside -- or NR, which is a form of vitamin B and a building block of NAD -- and pterostilbene, a compound found in blueberries. Elysium says both activate sirtuins.

Today Elysium has seven supplements. Guarente said he recruited prominent scientists to the board to lend gravitas to and help guide Elysium's work.

"Lenny wanted to collect an amazing scientific advisory board," said George Church, a Harvard geneticist who was on the board until late last year.

Church said he joined the board because he valued Guarente's commitment to running clinical trials. "Normally I would not be involved with supplements because I think they have low efficacy," he said.

Church, whose projects include trying to revive the woolly mammoth, co-founded his own antiaging company in 2018 that is trying to develop a gene therapy that would require FDA approval. "I think aging is a much more complicated thing to fix. I am doubling down on gene therapies," he said.

Elysium's first clinical trial involved 120 healthy older people who received either a single or double dose of the Basis supplement or a placebo. The company published a study in 2017 that showed both doses increased NAD levels over eight weeks compared with the placebo group.

Dr. Eric Verdin, CEO and president of the Buck Institute for Research on Aging in Novato, Calif., an independent research institution, has worked on sirtuins and NAD for more than 25 years. He has also founded or co-founded several longevity companies, including a new one that's developing therapeutic plasma exchange -- which involves replacing patients' blood plasma -- as a possible antiaging therapy.

He said sirtuins remain promising targets that are worth studying. Still, he added that "the more you study something, the more you understand the complexity. There is no magic pill -- even though we all would love the idea that there's going to be something magical that solves all of your problems and prevents you from aging."

One issue hanging over supplement companies including Elysium is a dispute over selling supplements that other companies are testing as drugs, something the FDA prohibits.

Elysium's supplements include one containing NMN, a building block of NAD. Metro International Biotech -- a company co-founded by Sinclair, Guarente's former protege -- is developing a version of NMN that it hopes might someday be approved by the FDA to treat age-related diseases such as Alzheimer's. The FDA said in 2023 that under current regulations, NMN shouldn't be marketed as a supplement, a position Metro advocated.

The Natural Products Association, a trade group representing retailers and supplement makers including Elysium, sued the FDA last year to clarify its regulations and allow NMN to continue to be sold. A judge gave the FDA until July to respond.

Elysium currently sells its NMN supplement through its website, and a spokeswoman said Metro's position was "entirely motivated by a perceived ability to make a larger profit."

Metro said the company had been investigating NMN in FDA-authorized trials before any legal sales of NMN by supplement companies.

Sinclair, who is on the company's scientific advisory board but doesn't have a management role, said, "I believe people should have access to supplements and medicines, but they should be tested for purity, safety and efficacy." In a statement posted on X, he said the work of bringing NMN to market as an FDA-approved drug to treat age-related diseases is in the best interest of patients.

Guarente and Sinclair continue to work together, including on a company they co-founded in 2017, Galilei Biosciences, which is also involved in sirtuins.

Guarente continues to write and speak about connections among sirtuins, NAD levels and longevity. Elysium started a long-term study in 2023 that aims to enroll 25,000 people and look for connections between lifestyle, health and aging. Around 2,500 have enrolled so far, and some have shared blood work results and medical history, according to Elysium.

Guarente said that despite past challenges, studies have validated sirtuins' importance in aging. He pointed to a 2022 study reporting that a mutation in a sirtuin gene found in some centenarians might contribute to their longevity.

He isn't giving up on the idea of longevity science.

"It is a little more complicated than inventions that have led to progress," he said. "The automobile is so tangible. It speaks for itself. This does not speak for itself. It needs a spokesperson."" [1]

1.  Scientists Clash Over Longevity --- Antiaging movement has raced ahead amid fierce debates over its theories. Marcus, Amy Dockser.  Wall Street Journal, Eastern edition; New York, N.Y.. 24 Mar 2025: A1.