MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases.

International journal of molecular sciences2022PMID: 36233287

View on PubMed DOI: 10.3390/ijms231911991

Plain Language Summary

Review examining MOTS-c's biology and therapeutic potential in human aging and age-related diseases—including diabetes, cardiovascular disease, osteoporosis, postmenopausal obesity, and Alzheimer's disease—covering its nuclear translocation under stress, AICAR-AMPK activation, and age-related decline in plasma levels that may contribute to the pathophysiology of aging. Provides a comprehensive aging-biology MOTS-c reference. Establishes MOTS-c as a key mitochondrial hormone whose age-related decline contributes to multiple aging diseases simultaneously—suggesting that supplementation could address the progressive mitochondrial peptide deficiency that underlies the increased vulnerability to metabolic, cardiac, skeletal, and neurological disease in older adults.

Abstract

MOTS-c, a 16 amino acid mitochondrial derived peptide, is encoded from the 12S rRNA region of the mitochondrial genome. Under stress conditions, MOTS-c translocates to the nucleus where it regulates a wide range of genes in response to metabolic dysfunction. It is colocalized to mitochondria in various tissues and is found in plasma, but the levels decline with age. Since MOTS-c has important cellular functions as well as a possible hormonal role, it has been shown to have beneficial effects on age-related diseases including Diabetes, Cardiovascular diseases, Osteoporosis, postmenopausal obesity and Alzheimer. Aging is characterized by gradual loss of (mitochondrial) metabolic balance, decreased muscle homeostasis and eventual diminished physical capability, which potentially can be reversed with MOTS-c treatment. This review examines the latest findings on biological effects of MOTS-c as a nuclear regulatory peptide and focuses on the role of MOTS-c in aging and age-related disorders, including mechanisms of action and therapeutic potential.

Authors

Mohtashami, Zahra; Singh, Mithalesh K; Salimiaghdam, Nasim; Ozgul, Mustafa; Kenney, M Cristina

Keywords

MOTS-cage-related diseasesagingmitochondrial derived peptidesmitochondrial dysfunction