Long-term treatment with Elamipretide enhances healthy aging phenotypes in mice

Abstract

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. In conclusion, 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. Keywords: Aging, mitochondria, elamipretide, C57BL/6 mice, high fat and sugar diet

Konjac Glucomannan Counteracted the Side Effects of Excessive Exercise on Gut Microbiome, Endurance, and Strength in an Overtraining Mice Model

“…The maximum grip force test was conducted by an XR501 Grip Strength Meter (Shanghai XINRUAN Information Technology Co., Ltd., Shanghai, China). Mice were stretched parallelly on a force-meter rod using their forelimb, and the tail was pulled in the opposite direction until the grasp was broken [20]. Mice were tested 5 consecutive times, and the maximum value was recorded.…”

Older-aged C57BL/6 mice fed a diet high in saturated fat and sucrose for ten months show decreased resilience to aging

“…The HFS diet (Bioserv, 3282, paste, gamma irradiated) has been described [9]. Briefly, it consisted of lard, sucrose, casein, maltodextrin, vitamins and minerals with 36 percent fat, 36 percent carbohydrate, and 20 percent protein.…”

“…Echocardiography is a non-invasive procedure that allows the assessment of systolic and diastolic function in mice. A Seimans Acuson CV-70 system with standard imaging planes was used to measure myocardial performance index (MPI) and diastolic function (Ea/Aa ratio) as described [9]. Rotarod performance is a measure of balance and coordination, and was assessed as the ability of mice to maintain balance on a rotating rod using a Rotamex 4/8 (Columbus Instruments, Inc.) with an accelerating rod protocol as described [11].…”