Determining the healthspan and senescent cell and DNA damage response status in long-lived mice with germline and adult-onset growth hormone receptor disruption
Congenital decrease in growth hormone (GH) action in mice has been associated with lifespan extension and with several improved markers of healthspan, including improved insulin sensitivity, resistance to diabetes and cancer, and a slower neuromuscular decline, making inhibition of GH receptor (GHR) a promising pharmacological intervention to extend healthy aging. The big question is how late in life can this approach provide the expected benefits? Dr. Duran-Ortiz works at answering this by switching off the GH axis at multiple ages in mice. Recently she reported that even at the adult age, GHR inhibition allows significant extension of lifespan in female mice and improves several metabolic markers of healthspan. This AFAR fellowship will help evaluate: (1) the frailty and healthspan status, and (2) the underlying molecular mechanisms responsible for their lifespan extension in these mice and thus clarify the nature of the gero-therapeutic effects of suppressing GH action in adulthood.
