PGC-1α, a potential therapeutic target against kidney aging

Aging Cell. 2019 Oct;18(5):e12994. doi: 10.1111/acel.12994. Epub 2019 Jul 16.

Abstract

Aging is defined as changes in an organism over time. The proportion of the aged population is markedly increasing worldwide. The kidney, as an essential organ with a high energy requirement, is one of the most susceptible organs to aging. It is involved in glucose metabolism via gluconeogenesis, glucose filtration and reabsorption, and glucose utilization. Proximal tubular epithelial cells (PTECs) depend on lipid metabolism to meet the high demand for ATP. Recent studies have shown that aging-related kidney dysfunction is highly associated with metabolic changes in the kidney. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), a transcriptional coactivator, plays a major role in the regulation of mitochondrial biogenesis, peroxisomal biogenesis, and glucose and lipid metabolism. PGC-1α is abundant in tissues, including kidney PTECs, which demand high energy. Many in vitro and in vivo studies have demonstrated that the activation of PGC-1α by genetic or pharmacological intervention prevents telomere shortening and aging-related changes in the skeletal muscle, heart, and brain. The activation of PGC-1α can also prevent kidney dysfunction in various kidney diseases. Therefore, a better understanding of the effect of PGC-1α activation in various organs on aging and kidney diseases may unveil a potential therapeutic strategy against kidney aging.

Keywords: PGC-1α; kidney aging; lipid metabolism; mitochondria; peroxisome.

Publication types

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

MeSH terms

  • Aging / drug effects
  • Aging / metabolism*
  • Humans
  • Kidney Diseases / drug therapy
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Molecular Targeted Therapy*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / antagonists & inhibitors*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*

Substances

  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha