There is a need for a Health span and Longevity Core to coordinate efforts of projects into a common goal to test the long term effects of SS-31 on age-related physiological function and lifespan in mice. These effects are not yet known at the multisystem level and the proposed experiments will shed new light on the ability to target mitochondria with a compound that is predicted to delay or reverse aging and age-related comorbid diseases. Use of a depot parenteral delivery will eliminate the need to do daily injections and provide a means of long term administration in preclinical studies and in human studies. The depot delivery concept is a significant approach to enhancing the value of the peptide. The underlying hypothesis is that SS-31 therapy initiated in middle age will forestall and protect the heart, skeletal muscle, vision and other health span metrics from intrinsic aging. It is not yet known whether SS-31 will extend lifespan (in any model organism) and this is a second important outcome of the efforts of Core B. Finally, application of a stressor can accelerate aging phenotypes, and the best model of this is a high fat diet (HFD), both because of its known deleterious effects on health span and lifespan metrics, as well as the unfortunate fact that obesity is epidemic in the human population. Thus, mice on a HFD model the aging of a large segment of humans.
Specific Aim 1 will determine murine lifespan and health span after SS-31 is continuously delivered to mice beginning at middle age. Pilot data will confirm health span phenotypes in C57BL/6 and the F1 BALB/cBy x C57BL/6 hybrid, followed by full cross sectional and lifespan cohorts with both genders.
Specific Aim 2 will determine the ability of SS-31 to attenuate the stress effects of a high fat diet (HFD) during aging. The protocol will follow that of Aim 1, but using a HFD. The data generated will provide valuable information on ways to further validate the peptide in preclinical studies and establish strategies for developing clinical anti-aging trials. Core B will address the resource objectives by providing colony management including old mouse monitoring and arrangements for colony management, and physiological assessment assays. Therefore, Core B will be enhancing the overall research goals of the P01.
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