Miranda Edwin R, Shahtout Justin L, Watanabe Shinya, Spaas Jan, Milam Norah Y, Neiswanger Grace, Werbner Benjamin, Stuart Deborah, Mookherjee Sohom, Wilson Jack, Judge Michael, Goh Isabella Y, Slater Tyler, Gallop Molly R, Hu Guoli, Karasawa Takuya, Landers Jillian K, Rainbow Bryann, O'Connor Kyle T, Black Nicholas J, Lan He, Nikolova Linda S, Li Ying, Davey Crystal F, Cox James E, Boudina Sihem, Karner Courtney M, Harasymowicz Natalia S, Ramkumar Nirupama, Symons J David, Chaix Amandine, Long Jonathan Z, Drummond Micah J, Funai Katsuhiko
Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah, United States.
Molecular Medicine Program, University of Utah, Salt Lake City, Utah, United States.
bioRxiv. 2025 Aug 25:2025.08.19.671148. doi: 10.1101/2025.08.19.671148.
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.
含组氨酸的二肽(HCDs),如N - 乙酰肌肽,是具有促能作用并减轻代谢功能障碍的内源性代谢产物。我们之前证明,短期N - 乙酰肌肽治疗在保护因废用引起的肌肉萎缩方面非常有效。在此我们证明,对雌性小鼠进行6个月的N - 乙酰肌肽治疗可减轻广泛的与年龄相关的疾病,并使存活率提高约50%。对器官系统的全面调查显示,N - 乙酰肌肽可防止肥胖、舒张功能、血管舒张、肌肉力量和骨密度下降。总之,N - 乙酰肌肽可显著延迟全系统终末期病理的发生,从而延长寿命。作为一种内源性存在的代谢产物,用N - 乙酰肌肽治疗可能是一种安全且有前景的促进人类健康衰老的干预措施。