Short of stumbling onto a genie or the Fountain of Youth, most of us accept aging as an inevitable part of life – but maybe it doesn't have to be. An emerging class of drugs called senolytics has been found to help restore the body to a more youthful state, and a new study has used a drug compound to extend the lifespan and improve the general health of older mice.
Normally cells will grow, replicate and die, but after a certain age they begin to lose their function. They'll stop dividing, but they also won't die, meaning they just sit there taking up space. These are known as senescent cells, and while the immune system naturally clears them out, gradually it loses its effectiveness. These defunct cells then begin to build up in the body, leading to the telltale physical signs of aging we're all too familiar with.
Certain diseases and treatments like chemotherapy have also been found to trigger senescence, and worse still, affected cells have been found to spread their lack of function to their neighbors. A recent study isolated a single gene that could turn on senescence, so silencing it could eventually lead to new treatments. Another past study found that senolytics can extend the lifespan of mice by up to 35 percent, while others didn't clear out senescent cells but rejuvenated them instead.
In the new study, researchers found more evidence that senescent cells are responsible for age-related ailments, and then treated them with senolytic compounds. First, the team injected young four-month-old mice with senescent cells, and found that just two weeks later they showed clear physical signs of aging. Compared to a control group that received injections of non-senescent cells, the walking speed, muscle strength, physical endurance, daily activity levels, food intake and body weight of the test mice were all reduced. At the same time, the numbers of senescent cells in their bodies increased, indicating the effect was spreading to healthy cells.
Next, the team treated both groups of mice with a senolytic compound, made up of two drugs called dasantinib and quercertin. After three days of treatment, the team found that the drug had killed many of the senescent cells and slowed down their physical deterioration.
To see whether the drug would also work on naturally-aged mice, the team injected 20-month-old animals with the D+Q treatment for four months, and found that it improved their physical wellbeing. The treated mice had higher walking speeds and daily activity levels, as well as better treadmill endurance and grip strength than other older mice.
The final test group was made up of very old mice, aged between 24 and 27 months. A biweekly treatment of D+Q senolytics was found to give them an average lifespan 36 percent longer than natural mice of their age.
"This is exciting research," says Felipe Sierra, who wasn't involved in the study. "This study clearly demonstrates that senolytics can relieve physical dysfunction in mice. Additional research will be necessary to determine if compounds, like the one used in this study, are safe and effective in clinical trials with people."
The research was published in the journal Nature Medicine.
Source: National Institutes of Health
