Presentation description

The aging population has increased the frailty burden of older individuals and socio-economic infrastructure. Currently, there is no clinically approved treatment for age-related functional decline creating demand for the development of such treatments. Carbonyls are reactive metabolites that accumulate in contexts of increased oxidative stress, such as aging. This carbonyl stress damages macromolecules such as proteins, lipids, and DNA. For example, our lab demonstrated that carbonyl stress is exacerbated in muscles undergoing atrophy due to a hindlimb unloading (HU) model of inactivity. Importantly, the accumulation of proteins modified by the reactive lipid carbonyl 4-Hydroxy-Nonenal, as well as muscle dysfunction and atrophy, were attenuated in HU mice treated with the carbonyl-scavenging dipeptide N-acetyl-carnosine. Therefore, we hypothesized that N-acetyl-carnosine could prevent carbonyl stress in other contexts, such as aging and other tissues beyond muscle. To test these hypotheses, we are monitoring the health of 18-month-old male and female mice over six months. During this period, the mice will be either given normal or N-acetyl-carnosine-supplemented water. Of the tissues and organ systems tested, N-acetyl-carnosine treatment attenuated loss in heart diastolic function, kidney function, bone density, and ex vivo muscle force production. We did not observe any attenuation of liver or brain dysfunction. We anticipate observing attenuated carbonyl stress in the heart, kidney, and muscle tissue of N-acetyl-carnosine-treated mice. Conversely, we expect no effect of N-acetyl-carnosine on carbonyl stress in unaffected tissues. Identifying the efficacy of N-acetyl-carnosine to attenuate age-related carbonyl stress will provide rationale for this work to be translated into human studies.