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Mitochondria-derived peptides in aging and healthspan

Review · human · The Journal of clinical investigation · 2022 · DOI 10.1172/JCI158449 · PMID 35499074

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

This review discusses mitochondria-derived peptides (MDPs), microproteins encoded by small open reading frames within mitochondrial DNA, and their relationship to aging and healthspan. The authors describe eight MDPs published to date: humanin, MOTS-c, and SHLPs 1-6. The review summarizes recent advances in microprotein discovery, current understanding of MDPs in aging, and how this understanding may relate to age-related diseases including type 2 diabetes, cancer, and neurodegenerative diseases at the genomic, proteomic, and drug-development levels.

Abstract

The mechanisms that explain mitochondrial dysfunction in aging and healthspan continue to be studied, but one element has been unexplored: microproteins. Small open reading frames in circular mitochondria DNA can encode multiple microproteins, called mitochondria-derived peptides (MDPs). Currently, eight MDPs have been published: humanin, MOTS-c, and SHLPs 1-6. This Review describes recent advances in microprotein discovery with a focus on MDPs. It discusses what is currently known about MDPs in aging and how this new understanding could add to the way we understand age-related diseases including type 2 diabetes, cancer, and neurodegenerative diseases at the genomic, proteomic, and drug-development levels.

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