[Regulation of Aging and Lifespan by White Adipose Tissue]

Yakugaku Zasshi. 2024;144(4):411-417. doi: 10.1248/yakushi.23-00165-4.
[Article in Japanese]

Abstract

Long-term caloric restriction (CR) is an effective intervention that improves whole-body metabolism, suppresses age-related pathophysiology, and extends lifespan. Although the beneficial effects of caloric restriction mediated by growth hormone/insulin-like growth factor-1 (GH/IGF-1) have been extensively studied, the mechanisms independent of GH/IGF-1 remain largely unknown. In this review, we focus on these GH/IGF-1-independent mechanisms, with a particular emphasis on the role of sterol regulatory element-binding protein 1c (SREBP-1c). CR increases the expression of SREBP-1c through the suppression of leptin signaling and enhances downstream factors involved in fatty acid synthesis in white adipose tissue (WAT). SREBP-1c also directly and indirectly increases the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, a master regulator of mitochondrial biogenesis, leading to an increase in the number of mitochondria. Furthermore, SREBP-1c elevates expression of mitochondrial intermediate peptidase, which contributes to improving mitochondrial quality through the processing of sirtuin 3 into its mature form. Thus, it appears that CR exerts beneficial effects by modulating mitochondrial quantity and quality in WAT in a GH/IGF-1 signal-independent manner.

Keywords: aging; caloric restriction; fatty acid synthesis; mitochondria; sterol regulatory element-binding protein 1c (SREBP-1c); white adipose tissue (WAT).

Publication types

  • Review
  • English Abstract

MeSH terms

  • Adipose Tissue, White / metabolism
  • Insulin-Like Growth Factor I* / metabolism
  • Longevity*
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism

Substances

  • Insulin-Like Growth Factor I
  • Sterol Regulatory Element Binding Protein 1