Nickel Katie, Zhu Lida, Mangalindan Ruby, Snyder Jessica M, Tucker Matthew, Whitson Jeremy, Sweetwyne Maryia, Valencia Ana P, Klug Jenna, Jiang Zhou, Marcinek David J, Rabinovitch Peter, Ladiges Warren
Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Department of Biology, Davidson College, Davidson, NC, USA.
Aging Pathobiol Ther. 2022;4(3):76-83. doi: 10.31491/apt.2022.09.089. Epub 2022 Sep 30.
Disruption of metabolic and bioenergetic homeostasis related to mitochondrial dysfunction is a key driver of aging biology. Therefore, targeting mitochondrial function would be a rational approach to slowing aging. Elamipretide (Elam, a.k.a. SS-31) is a peptide known to target mitochondria and suppress mammalian signs of aging. The present study was designed to examine the phenotypic effects of long-term Elam treatment on aging in C57BL/6 mice starting at 18 months of age.
Mice were fed regular chow (RC diet) or a diet high in fat and sugar (HF diet) and treated with 3 mg/kg of Elam or saline subcutaneously 5 days per week for 10 months. Physiological performance assessments were conducted at 28 months of age.
Elam improved the physical performance of males but not females, while in females Elam improved cognitive performance and enhanced the maintenance of body weight and fat mass. It also improved diastolic function in both males and females, but to a greater extent in males. The HF diet over 10 months had a negative effect on health span, as it increased body fat and decreased muscle strength and heart function, especially in females.
Elam enhanced healthy aging and cardiac function in both male and female mice, although the specific effects on function differed between sexes. In females, the treatment led to better cognitive performance and maintenance of body composition, while in males, performance on a rotating rod was preserved. These overall observations have translational implications for considering additional studies using Elam in therapeutic or preventive approaches for aging and age-related diseases.
与线粒体功能障碍相关的代谢和生物能量稳态破坏是衰老生物学的关键驱动因素。因此，针对线粒体功能将是延缓衰老的合理方法。伊拉米肽（Elam，又名SS-31）是一种已知可作用于线粒体并抑制哺乳动物衰老迹象的肽。本研究旨在研究从18个月大开始长期使用伊拉米肽治疗对C57BL/6小鼠衰老的表型影响。
小鼠喂食常规饲料（RC饮食）或高脂肪高糖饮食（HF饮食），并每周5天皮下注射3mg/kg伊拉米肽或生理盐水，持续10个月。在28个月大时进行生理性能评估。
伊拉米肽改善了雄性小鼠的身体性能，但对雌性小鼠没有效果，而在雌性小鼠中，伊拉米肽改善了认知性能，并增强了体重和脂肪量的维持。它还改善了雄性和雌性小鼠的舒张功能，但对雄性小鼠的改善程度更大。10个月的HF饮食对健康寿命有负面影响，因为它增加了体脂，降低了肌肉力量和心脏功能，尤其是在雌性小鼠中。
伊拉米肽增强了雄性和雌性小鼠的健康衰老和心脏功能，尽管对功能的具体影响在性别之间有所不同。在雌性小鼠中，该治疗导致更好的认知性能和身体成分维持，而在雄性小鼠中，保留了在转棒试验中的表现。这些总体观察结果对于考虑使用伊拉米肽进行衰老和年龄相关疾病的治疗或预防方法的进一步研究具有转化意义。
