Some researchers argue that only the “healthspan” -- the period of life free of illness -- is worth extending. Of course, a healthy lifestyle can add years to most people’s lives and actually improve cellular aging. Some of the biggest payoffs come from quitting or never smoking, logging more than 5½ hours of physical activity per week, and keeping a normal weight.
Drugs may be able to do that as well by interrupting common markers of aging, including telomere length, inflammation, oxidative stress, and slower cell metabolism.
“You don’t have to target all of these hallmarks to get improvement” in healthspans, says Barzilai, who also is director of the Institute for Aging Research at the Albert Einstein College of Medicine in the Bronx and scientific director of the American Federation for Aging Research.
“If you target one, you show benefit in the others.”
The medical term for growing old is senescence. Buffeted by DNA damage and stresses, your cells deteriorate and eventually stop multiplying, but don’t die.
That slowdown may have big consequences for your health. Your genes become more likely to get mutations, which can pave the way for cancer. Mitochondria, which produce energy in the cell, struggle to fuel your body. That can damage cells and cause chronic inflammation, which plays a part in diabetes, arthritis, ulcerative colitis, and many other diseases.
One major hallmark of aging is the growing stockpile of these senescent cells. Damaged cells become deactivated as a way to protect your body from harmful or uncontrolled cell division. But like the rotten apple that spoils the whole bunch, senescent cells encourage their neighbors to turn dysfunctional, too. They also emit proteins that trigger inflammation. Your body naturally removes these dormant cells. But older immune systems have a harder time cleaning up, so the senescent cells are more likely to hang around.
Flushing out this accumulated debris may be one way to avert aging, some experts say.
De Grey also believes that could be done with drugs.
“These therapies would actually repair [cellular] damage,” he says. “They’ll eliminate damage from the body by resetting or turning back the clock.”
James Kirkland, MD, Ph.D., of the Mayo Clinic is one researcher exploring this theory. He gave a mixture of the cancer drug dasatinib and a plant pigment called quercetin to people with diabetic kidney disease. Quercetin is an antioxidant that gives grapes, tomatoes, and other fruits and vegetables their flavor.
A small phase I clinical trial showed that the dasatinib-quercetin combination got rid of senescent cells in the tissues of people with the disease.
The researchers don’t know yet if the results will translate into prolonged youth. They also don’t know how high a dosage is needed and what long-term problems the treatment might cause. People with chronic leukemia take dasatinib for years with few serious ill effects.
In another recent study, scientists used oxygen therapy to tackle senescent cells. Thirty-five adults ages 64 and older received oxygen therapy in a pressurized chamber. After 60 daily sessions, they showed a decrease in senescent cells and improvement to the length of DNA segments called telomeres. Shortened segments of telomeres are thought to be another marker of aging.
Researchers are also looking to the gene-editing technology CRISPR for anti-aging treatments, but the testing is only in mice so far.
Barzilai hopes that if the metformin trial succeeds, it will open the floodgates to a wave of new drugs that can stop or reverse human aging. Some of the major players in this field include Juvenescence, AgeX Therapeutics, LyGenesis, and Life Biosciences, which Barzilai founded.
“Until aging is seen as preventable, health plans won’t have to pay for this type of treatment,” he says. And if health plans won’t cover aging, pharmaceutical companies have little incentive to invest in drug development.
That may be the only thing standing between humans and unprecedented lifespans. The Census Bureau projects that Americans born in 2060 should live an average of 85.6 years, up from 78.7 years in 2018. De Grey’s prediction tops that mark by a factor of about 50. He believes that the life expectancy for someone born in 2100 may well be 5,000 years.
Barzilai, for his part, has a prediction that’s seemingly more modest.
“We die at 80. Getting an additional 35 years is relatively low-hanging fruit,” he says. “But I don’t believe that is a fixed limit.”