The problem begins with the fact that our cells, like ourselves, have a finite life span. After dividing about 50 times, many types of cells reach the Hayflick limit, where they simply run out of gas and quit multiplying. This, it’s long been thought, is why we lose our ability to regenerate and heal: Things sag, bag, and go kaput.
But more recently, scientists have realised that the real problem is what those cells do after they’re done dividing. At that point, they can enter a senescent state, where they’re basically retired but not dead. Rather than just sitting there quietly, however, senescent cells can spew out a toxic brew of inflammatory factors that poisons the cells around them. Some researchers believe they could be partly responsible for some of the aspects of ageing – everything from cataracts to cancer.
“Senescent cells are clearly bad and contribute to the ageing process,” says Laura Niedernhofer, a DNA researcher at the Scripps Institute in Jupiter, Florida. “So there’s been a race to find drugs that can target them.”
Lately, the race took a huge leap forward. A study co-authored by Niedernhofer showed that two relatively well-known compounds appeared to kill senescent cells in mice while leaving normal cells intact. Previously, senescent cells had been thought to be hard to isolate and purge. But in mice whose muscles had been prematurely aged by radiation, the combination was shown to restore their youthful spring. Elderly mice on the same treatment experienced improved heart function. Even better, both compounds have already been cleared for other uses: Dasatinib is an FDA-approved leukaemia drug, and quercetin is a common antioxidant flavonoid sold as a supplement that is found in, among other things, cilantro, onions, capers, and, of course, kale.
In other studies, zapping senescent cells has also been shown to stem the loss of subcutaneous fat, a “good” kind of fat that makes skin appear smooth but that we lose with age. “We hope that clearing senescent cells will have widespread health benefits,” says Judith Campisi, a cell and molecular biologist at the Buck Institute for Research on Aging in Marin County, California, who has studied cells senescence for more than two decades. According to Campisi, those benefits may include preventing atherosclerosis, osteoarthritis, some cancers, and Parkinson’s disease – and several other senescent-clearing drugs are being studied.
Clinical trials are already being planned for the dasatinib-quercetin combination, but study senior author James Kirkland, director of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic in Rochester, Minnesota, warns that it’s too soon for people to use them because of the unknown side effects.
EXERCISE IN A PILL?
Another trouble spot in our cells is the mitochondria, the tiny cellular energy plants that convert nutrients to fuel. As we get older, mitochondria lose their ability to function – perhaps contributing to cell senescence – but scientists have long noted that exercising seems to help keep them in tune. A team at the University of Southern California Leonard Davis School of Gerontology identified a peptide produced in the mitochondria that appears to mimic many of the benefits of exercise, such as improved metabolism and increased insulin sensitivity; mice who were injected did not become obese, despite eating all they wanted.
“It acts like exercise; that’s very clear,” says study senior author Pinchas Cohen of the peptide, called MOTS-c. “It increases energy expenditure, which is what we measured.” But, he cautions, any “exercise pill” is at least five years away – which means you still have to hit the gym, for now.