… Within the last decade or so, researchers have settled upon what Felipe Sierra, director of the division of aging biology at the National Institute on Aging (NIA), calls “the major pillars of aging.” These pathways and mechanisms, roughly half a dozen in all, affect metabolism, growth, response to stress, stem cell vigor, inflammation, and proteostasis—the cell’s quality control system for proteins. And their identification has opened the door to a previously outlandish notion. It “allows us to think that, okay, if we understand how this happens, we can maybe manipulate it,” Sierra says.
MORE THAN A DECADE AGO, Barzilai and others began lobbying FDA to consider drugs that might do just that. But those discussions bogged down, he says, after the sides couldn’t agree on the kinds of biomarkers associated with aging that could be quantified and tracked during a clinical trial.
Barzilai now believes the answer is to design a drug trial that, rather than targeting aging per se, tries instead to delay the onset of “comorbidities”: the chronic diseases whose incidence rises sharply as people get older. “Basically, I think the FDA will be more willing to accept something called ‘comorbidities’ than it is to accept something called ‘aging,’” Barzilai says. “Even in our mind, in my mind, aging is not a disease,” he adds. “It’s, you know, humanity! You’re born, you die, you age in between … I’m kind of saying, ‘I don’t care what they want to call it, if I can delay it.’”
The comorbidity strategy is key to a concept known as the “longevity dividend,” first proposed by a group of public policy and health care experts in 2006. The idea is that slowing down the process of aging, even modestly, would have enormous benefits for quality of life and the economics of health care. “We’re not arguing—and we’ve never argued—that we’re trying to achieve life extension,” says Olshansky, who has pushed the concept while criticizing some of the more outlandish claims in the aging field, such as British gerontologist Aubrey de Grey’s prediction that human life spans of 1000 years are possible. “We’ll probably live a little longer if we succeed, but that’s not the goal,” Olshansky says. “The goal is the extension of the period of healthy life.” …
… But the FDA drug approval process abides by the “one disease, one drug” model. Would the agency be open to a trial that had multiple illnesses as an endpoint? As an initial step, earlier this year Sierra organized seminars at FDA in which NIA researchers described recent findings in the biology of aging. In May, Robert Temple, deputy director of FDA’s Center for Drug Evaluation and Research, spoke at an NIA retreat.
Encouraged by the tenor of these discussions, Barzilai and a core group of collaborators—Einstein’s Jill Crandall; Austad; Olshansky; Stephen Kritchevsky at Wake Forest School of Medicine (where the multi-center trial would probably be based); and James Kirkland, a diabetes researcher at the Mayo Clinic, among others—pushed ahead with plans for the trial. …
… SANDY WALSH, an FDA spokeswoman, says the agency does not comment on drugs under development or under investigation. But in a followup communication to the AFAR group, Barzilai says, FDA indicated that although it is not yet convinced that the proposed trial design can establish that metformin has an anti-aging effect, the agency recognizes the potential value in a drug that could improve quality of life and survival—whether the indication sought is aging or multiple morbidities—and is not opposed to the idea of a trial. …