N-acetylcarnosine attenuates age-associated declines in multi-organ systems to improve survival

Miranda, E. R.; Shahtout, J. L.; Watanabe, S.; Spaas, J.; Milam, N. Y.; Neiswanger, G.; Werbner, B.; Stuart, D.; Mookherjee, S.; Wilson, J.; Judge, M.; Goh, I. Y.; Slater, T.; Gallop, M. R.; Hu, G.; Karasawa, T.; Landers, J. K.; Rainbow, B.; O'Connor, K. T.; Black, N. J.; Lan, H.; Nikolova, L. S.; Li, Y.; Davey, C. F.; Cox, J. E.; Boudina, S.; Karner, C. M.; Harasymowicz, N. S.; Ramkumar, N.; Symons, J. D.; Chaix, A.; Long, J. Z.; Drummond, M. J.; Funai, K.

doi:10.1101/2025.08.19.671148

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bioRxiv · 10.1101/2025.08.19.671148

N-acetylcarnosine attenuates age-associated declines in multi-organ systems to improve survival

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Abstract

Histidine containing dipeptides (HCDs) such as N-acetylcarnosine are endogenous metabolites that are ergogenic and mitigate metabolic dysfunction. We previously demonstrated that short-term N-acetylcarnosine treatment is highly efficacious in protecting muscle atrophy induced by disuse. Here we demonstrate that a 6-months treatment of N-acetylcarnosine attenuates a broad spectrum of age-associated maladies and improved survival by [~]50% in female mice. A comprehensive survey of organ systems revealed that N-acetylcarnosine prevents decline in adiposity, diastolic function, vasodilation, muscle strength, and bone density. Together, N-acetylcarnosine substantially delays the onset of system-wide end-stage pathology to prolong lifespan. As an endogenously present metabolite, treatment with N-acetylcarnosine may be a safe and promising intervention to promote healthy aging in humans.

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Miranda, E. R., Shahtout, J. L., Watanabe, S., Spaas, J., Milam, N. Y., Neiswanger, G., Werbner, B., Stuart, D., Mookherjee, S., Wilson, J., Judge, M., Goh, I. Y., Slater, T., Gallop, M. R., Hu, G., Karasawa, T., Landers, J. K., Rainbow, B., O'Connor, K. T., Black, N. J., Lan, H., Nikolova, L. S., Li, Y., Davey, C. F., Cox, J. E., Boudina, S., Karner, C. M., Harasymowicz, N. S., Ramkumar, N., Symons, J. D., Chaix, A., Long, J. Z., Drummond, M. J., Funai, K.. 2025-08-22. N-acetylcarnosine attenuates age-associated declines in multi-organ systems to improve survival. https://doi.org/10.1101/2025.08.19.671148

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