Just as with rapamycin, this treatment seems to provide longevity benefits without changing epigenetic age measures:
Aging-related decreases in cardiac and skeletal muscle function are strongly associated with various comorbidities. Elamipretide (ELAM), a novel mitochondria-targeted peptide, has demonstrated broad therapeutic efficacy in ameliorating disease conditions associated with mitochondrial dysfunction across both clinical and pre-clinical models. Herein, we investigated the impact of 8-week ELAM treatment on pre- and post-measures of C57BL/6J mice frailty, skeletal muscle, and cardiac muscle function, coupled with post-treatment assessments of biological age and affected molecular pathways. We found that health status, as measured by frailty index, cardiac strain, diastolic function, and skeletal muscle force, is significantly diminished with age, with skeletal muscle force changing in a sex-dependent manner. Conversely, ELAM mitigated frailty accumulation and was able to partially reverse these declines, as evidenced by treatment-induced increases in cardiac strain and muscle fatigue resistance. Despite these improvements, we did not detect statistically significant changes in gene expression or DNA methylation profiles indicative of molecular reorganization or reduced biological age in most ELAM-treated groups. However, pathway analyses revealed that ELAM treatment showed pro-longevity shifts in gene expression, such as upregulation of genes involved in fatty acid metabolism, mitochondrial translation, and oxidative phosphorylation, and downregulation of inflammation. Together, these results indicate that ELAM treatment is effective at mitigating signs of sarcopenia and cardiac dysfunction in an aging mouse model, but that these functional improvements occur independently of detectable changes in epigenetic and transcriptomic age. Thus, some age-related changes in function may be uncoupled from changes in molecular biological age.
Open access paper:
https://onlinelibrary.wiley.com/doi/10.1111/acel.70026
Related:
Elamipretide (also known as SS-31, MTP-131 and Bendavia)[1][2] is a small mitochondrially-targeted tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH2) that appears to reduce the production of toxic reactive oxygen species and stabilize cardiolipin.[3]
Stealth Peptides, a privately held company, was founded in 2006 to developintellectual property licensed from several universities including elamipretide; it subsequently changed its name to Stealth BioTherapeutics.[4][5]
As of November 2017 Stealth had obtained an orphan designation in the US for use in mitochondrial myopathy and had started a Phase III trial in that indication.[2] As of January 2020, trial expectations were not met.[6]
https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/elamipretide
