Aging, senescence and mitochondria: the PGC-1/ERR axis

J Mol Endocrinol. 2021 Jan;66(1):R1-R14. doi: 10.1530/JME-20-0196.

Abstract

Aging is a degenerative process that results from the accumulation of cellular and tissue lesions, leading progressively to organ dysfunction and death. Although the biological basis of human aging remains unclear, a large amount of data points to deregulated mitochondrial function as a central regulator of this process. Mounting years of research on aging support the notion that the engendered age-related decline of mitochondria is associated with alterations in key pathways that regulate mitochondrial biology. Particularly, several studies in the last decade have emphasized the importance of the estrogen-related receptor (ERR) family of nuclear receptors, master regulators of mitochondrial function, and their transcriptional coactivators PGC-1s in this context. In this review, we summarize key discoveries implicating the PGC-1/ERR axis in age-associated mitochondrial deregulation and tissue dysfunction. Also, we highlight the pharmacological potential of targeting the PGC-1/ERR axis to alleviate the onset of aging and its adverse effects.

Keywords: aging; metabolism; mitochondrion; nuclear receptors; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / physiology*
  • Animals
  • Biomarkers
  • Cellular Senescence
  • Humans
  • Mitochondria / physiology*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Biomarkers
  • Receptors, Estrogen
  • Transcription Factors
  • peroxisome-proliferator-activated receptor-gamma coactivator-1