Mitochondria-derived peptides in healthy ageing and therapy of age-related diseases

Adv Protein Chem Struct Biol. 2023:136:197-215. doi: 10.1016/bs.apcsb.2023.02.015. Epub 2023 Apr 25.

Abstract

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.

Keywords: Age-related macular degeneration; Ageing; Alzheimer’s disease; Healthspan; Humanin; Lifespan; MOTS-c; Mitochondria-derived peptides; SHLPs.

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / therapy
  • Healthy Aging*
  • Humans
  • Mitochondria / genetics
  • Peptides

Substances

  • Peptides