Tuesday, March 01, 2016

Getting rid of old cells extends lifespan of mice and ameliorates age-related diseases.

Baker et al. show that getting rid of cells that have entered an irreversible senescent state expands the lifespan of mice and ameliorates some age-related disease processes. Clips from the Gil and Withers summary of the work:
More than 50 years ago, it was suggested that ageing is linked to a state of arrested cell growth known as senescence, but this link has remained unproven, and the molecular basis for organismal ageing has been elusive...Senescence is a cellular state in which cells permanently stop dividing. It is mediated by two signalling pathways — the p53 pathway and the p16Ink4a–Rb pathway. Senescent cells secrete a complex cocktail of factors called the senescence-associated secretory phenotype (SASP), which includes matrix metalloproteinases (enzymes that break down the extracellular matrix) and pro-inflammatory signalling molecules. Such cells have been shown to accumulate during ageing, and their presence has been associated with a broad range of diseases, including diabetes, kidney disease and many cancers.
Baker et al. demonstrate that the removal of senescent cells does indeed delay ageing and increase healthy lifespan (healthspan)...using a genetically engineered mouse model that they had developed previously4, called INK–ATTAC. These mice produce a caspase enzyme specifically in cells that express the p16Ink4a gene. The caspase can be activated by the injection of a drug; the activated caspase then triggers cell death, eliminating senescent cells in which it is expressed...[They] found that the elimination of p16Ink4a-expressing cells increased lifespan, regardless of the sex or strain of mouse examined, and ameliorated a range of age-dependent, disease-related abnormalities, including kidney dysfunction and abnormalities in heart and fat tissue.

1 comment:

  1. Exercise probably helps in the removal of senescent cells.