Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice.

The pathology of aging impacts multiple organ systems, including the kidney and skeletal and cardiac muscles. Long-term treatment with the mitochondrial-targeted peptide elamipretide has previously been shown to improve in vivo mitochondrial function in aged mice, which is associated with increased fatigue resistance and treadmill performance, improved cardiovascular diastolic function, and glomerular architecture of the kidney. However, elamipretide is a short tetrameric peptide that is not orally bioavailable, limiting its routes of administration. This study tested whether twice weekly intermittent injections of elamipretide could recapitulate the same functional improvements as continuous long-term infusion. We found that intermittent treatment with elamipretide for 8 months preserved exercise tolerance and left ventricular mass in mice with modest protection of diastolic function and skeletal muscle force production but did not affect kidney function as previously reported using continuous treatment.