Review covering recent advances in mitochondria-derived peptides—humanin, MOTS-c, and SHLPs 1–6—in aging and healthspan, including their discovery, mechanisms of action, age-related decline, and emerging evidence for roles in age-related diseases including T2DM, cancer, and neurodegeneration, framing MDPs as an underexplored microprotein class with major implications for aging biology and drug development. Provides a broad aging-biology MDP overview. Establishes MDPs as a novel category of aging biology regulators that emerge from the mitogenome—arguing that the age-related decline in MOTS-c and humanin is not epiphenomenal but mechanistically contributes to age-related disease onset, with implications for genomic approaches to longevity.
Miller, Brendan; Kim, Su-Jeong; Kumagai, Hiroshi; Yen, Kelvin; Cohen, Pinchas