Mayo Clinic researchers extend lifespan by up to 35 percent in mice

February 3, 2016

Aged mice with and without senescent cell clearance (credit: Mayo Clinic)

Researchers at Mayo Clinic have discovered that senescent cells — cells that no longer divide and accumulate with age — shorten lifespan by as much as 35 percent in normal mice.

Removing these aging cells delays tumor formation, preserves tissue and organ function, and extends lifespan without observed adverse effects, the researchers found, writing Feb. 3 in Nature.

“Cellular senescence is a biological mechanism that functions as an ‘emergency brake’ used by damaged cells to stop dividing,” says Jan van Deursen, Ph.D., Chair of Biochemistry and Molecular biology at Mayo Clinic, and senior author of the paper. “While halting cell division of these cells is important for cancer prevention, it has been theorized that once the ‘emergency brake’ has been pulled, these cells are no longer necessary.”

As the immune system becomes less effective, senescent cells build up and damage adjacent cells, causing chronic inflammation, which is closely associated with frailty and age-related diseases.

Mayo Clinic researchers used a compound called AP20187 to remove senescent cells, which delayed tumor formation and reduced age-related deterioration of several organs, extending mediian lifespan of treated mice by 17 to 35 percent. The mice also had a healthier appearance and less inflammation in fat, muscle and kidney tissue.

The research was supported by the National Institutes of Health, the Paul F. Glenn Foundation, the Ellison Medical Foundation, the Noaber Foundation, and the Mayo Clinic Robert and Arlene Kogod Center on Aging.

Van Deursen is a co-inventor of the technology that has been licensed by Mayo Clinic to Unity Biotechnology. Mayo Clinic and Van Deursen have a financial interest in the technology.

Mayo Clinic | Researchers Extend Lifespan by as Much as 35 Percent in Mice

Abstract of Naturally occurring p16Ink4a-positive cells shorten healthy lifespan

Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16Ink4a (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16Ink4a-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16Ink4a-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16Ink4a-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.