Using mice, researchers have shown that clearing out senescent cells – cells whose ability to divide is permanently switched off and that accumulate with age – can increase lifespan without negative side effects.
In a Nature paper, the team – from the Mayo Clinic College of Medicine in Rochester, MN – describes how senescent cells harm health and shorten lifespan by as much as 35% in normal mice.
They report how eliminating senescent cells delays tumor formation, preserves tissue and organ function and extends lifespan – with no apparent adverse effects.
Senior author Jan van Deursen, a professor of pediatrics with a chair in biochemistry and molecular biology, explains:
“Cellular senescence is a biological mechanism that functions as an ’emergency brake’ used by damaged cells to stop dividing.”
Senescence can be triggered by stress that can cause cells to malfunction – so by halting cell division, it stops them growing abnormally and forming tumors.
Senescent cells may no longer replicate, but they are not dead or dormant and they secrete compounds such as growth factors and enzymes that affect other cells around them.
The authors note that some of the secreted compounds can damage neighboring cells and cause chronic inflammation, which is linked to age-related diseases.
The immune system routinely clears out senescent cells, but over time, this process becomes less effective, so senescent cells accumulate with age.
Previous studies have shown that senescence is linked to several biological processes – some of them good and some of them bad – but as Prof. van Deusen explains:
“Senescent cells that accumulate with aging are largely bad, do bad things to your organs and tissues, and therefore shorten your life but also the healthy phase of your life.”
For their study, the researchers inserted a gene into normal mice that primed their senescent cells to commit cell suicide when triggered by a drug called AP20187.
Removing senescent cells by this means delayed tumor formation and reduced age-related deterioration of several organs, note the authors.
They also found the treated mice lived 17-35% longer than untreated mice and appeared to be healthier, with less inflammation in fat, muscle and kidney tissue.
The researchers suggest that if the findings work in humans, then removing senescent cells may be a way not only for people to live longer but to be healthier for longer. First author Darren Baker, assistant professor of biochemistry and molecular biology, explains:
“If translatable, because senescent cells do not proliferate rapidly, a drug could efficiently and quickly eliminate enough of them to have profound impacts on healthspan and lifespan.”
He says their findings suggest clearance of just 60-70% of senescent cells could have significant therapeutic effects.
In the following video, Profs. van Deursen and Baker describe their study and its potential implications:
Meanwhile, Medical News Today recently learned about another study where researchers reversed aging in the brains of rats with a drug that regenerates the fibers that carry signals between brain cells.