Their removal, even at later age, halts or delays progression of tissue dysfunction in mice
THURSDAY, Nov. 3 (HealthDay News) -- Senescent cells have a causal association with age-related phenotypes, and removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan in mice with the BubR1 progeroid background, according to a letter published online Nov. 2 in Nature.
Darren J. Baker, Ph.D., from the Mayo Clinic College of Medicine in Rochester, Minn., and colleagues investigated whether senescent cells caused the development of age-related dysfunction, and whether their removal was beneficial in delaying or preventing age-related disorders and maximizing healthy lifespan. Using a biomarker for senescence, p16Ink4a, a novel transgene was designed (INK-ATTAC) which can induce elimination of p16Ink4a-positive senescent cells after administration of rosiglitazone.
The investigators found that, following drug administration, p16Ink4a-positive senescent cells were removed by INK-ATTAC in mice with the BubR1 progeroid background. Life-long removal of p16Ink4a-expressing cells delayed the onset of age-related pathologies in tissues in which accumulated p16Ink4a cells contribute to acquisition of these pathologies (adipose tissues, skeletal muscle, and eye). Progression of already established age-related disorders was reduced by late-life clearance of p16Ink4a-expressing cells.
"Our proof-of-principle experiments demonstrate that therapeutic interventions to clear senescent cells or block their effects may represent an avenue for treating or delaying age-related diseases and improving healthy human lifespan," the authors write.
Abstract
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