This paper reviews tiny proteins made by mitochondria, especially humanin, that help protect cells from stress, inflammation, and heart damage, and act like metabolic sensors linked to aging diseases. It suggests that boosting these peptides might help with brain health, eye health, and overall longevity, but it doesn’t give specific dosing or protocols.

Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by mitochondrial DNA and involved in various stress-protecting mechanisms. To date, eight mitochondrial-derived peptides have been identified: MOTS-c sequence is hidden in the 12 S rRNA gene (MT-RNR1), and the other 7 (humanin and small humanin-like peptides 1-6) are encoded by the 16 S rRNA (MT-RNR2) gene. While the anti-apoptotic, anti-inflammatory and cardioprotective activities of MDPs are well described, recent research suggests that MDPs are sensitive metabolic sensors, closely connected with mtDNA mutation-associated diseases and age-associated metabolic disorders. In this chapter, we focus on the recent progress in understanding the metabolo-protective properties of MDPs, their role in maintenance of the cellular and mitochondrial homeostasis associated with age-related diseases: Alzheimer's disease, cognitive decline, macular degeneration and cataracts. Also, we will discuss MDPs-based and MDPs-targeted interventions to treat age-related diseases and extend a healthy lifespan.