FoxO3 Regulates the Progress and Development of Aging and Aging-Related Diseases

Curr Mol Med. 2023;23(10):991-1006. doi: 10.2174/1566524023666221014140817.

Abstract

Aging is an inevitable risk factor for many diseases, including cardiovascular diseases, neurodegenerative diseases, cancer, and diabetes. Investigation into the molecular mechanisms involved in aging and longevity will benefit the treatment of age-dependent diseases and the development of preventative medicine for agingrelated diseases. Current evidence has revealed that FoxO3, encoding the transcription factor (FoxO)3, a key transcription factor that integrates different stimuli in the intrinsic and extrinsic pathways and is involved in cell differentiation, protein homeostasis, stress resistance and stem cell status, plays a regulatory role in longevity and in age-related diseases. However, the precise mechanisms by which the FoxO3 transcription factor modulates aging and promotes longevity have been unclear until now. Here, we provide a brief overview of the mechanisms by which FoxO3 mediates signaling in pathways involved in aging and aging-related diseases, as well as the current knowledge on the role of the FoxO3 transcription factor in the human lifespan and its clinical prospects. Ultimately, we conclude that FoxO3 signaling pathways, including upstream and downstream molecules, may be underlying therapeutic targets in aging and age-related diseases.

Keywords: Aging; FoxO3; aging-related diseases; cardiovascular diseases; longevity; neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging* / genetics
  • Forkhead Box Protein O3* / genetics
  • Humans
  • Longevity*
  • Neoplasms / genetics

Substances

  • Forkhead Box Protein O3
  • FOXO3 protein, human