Effects of N-Acetyl-Carnosine Treatment on Aging and Carbonyl Stress

Abstract

By 2050 the number of individuals over the age of 80y will triple to reach 426 million and the rate of age-related comorbidities has also increased precipitously as our global population has continued to age. Currently, there is no clinically approved treatment for age-related functional decline creating demand for the development of such treatments. Our lab previously demonstrated that carbonyl stress is exacerbated in muscles during a hindlimb unloading (HU) model of inactivity. Importantly, the accumulation of proteins modified by the reactive lipid carbonyl 4HNE, as well as muscle dysfunction and atrophy, were attenuated in HU mice treated with the carbonyl-scavenging dipeptide N-acetyl-carnosine (N-Ac-Carn). Therefore, we hypothesized that N-Ac-Carn could prevent carbonyl stress in aging muscles and other tissues. 17-month-old male and female C57Bl6J mice from the NIA colony were treated for 6-months with 80 mM N-Ac-Carn or normal (CON) water. Before and after the 6-month intervention we assessed several markers of health including glucose tolerance, kidney, muscle, bone, and cognitive function. N-Ac-Carn preserved ex vivo muscle force production in soleus ( p=0.0015) and EDL ( p=0.0008) muscles from female but not male mice. N-Ac-Carn treated mice also possessed superior bone volume compared to CON ( p=0.0046). Following terminal tissue collection, we also assessed muscles for carbonyl stress by probing for proteins modified by total carbonyls, 4HNE, MDA, and methylglyoxal. N-Ac-Carn did not attenuate 4HNE, MDA, or total carbonyls in gastrocnemius. However, N-Ac-Carn showed strong trends for attenuating 4HNE burden in both soleus and EDL muscles. N-Ac-Carn is an endogenously produced dipeptide that is safe for human consumption and affordable making it a promising therapeutic strategy for the mitigation of age-related functional decline. AG074535-02S2. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.