With a bit of clever genetic engineering, a team of scientists has just found an astonishing way to significantly expand the natural lifespan of mice. Now, at least one biotech company hopes to translate this breakthrough to fight aging in humans.
In a study published today in the journal Nature, medical researchers at Mayo Clinic College of Medicine—led by cell biologists Darren Baker and Jan van Deursen—have made this decade's biggest breakthrough in understanding the complex world of physical aging.
Ref: Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature (3 February 2016) | DOI: 10.1038/nature16932
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.