Mechanisms of aging-related impairment of brown adipocyte development and function

Gerontology. 2015;61(3):211-7. doi: 10.1159/000366557. Epub 2014 Dec 20.

Abstract

Aging is one of the primary risk factors for the development of obesity, a pathology that develops due to an imbalance of increased energy consumption over reduced expenditure. Brown adipocytes are responsible for thermogenesis and could therefore counter obesity by increasing energy expenditure. It is by now well established that humans possess thermogenesis-competent brown adipocytes throughout life, and recent findings indicate that brown fat is actively involved in metabolic control and body weight regulation in adults. Aging is accompanied by a loss of classical brown adipocytes as well as the brown-like adipocytes found in white adipose tissue, suggesting that loss of their energy-expending capacity might contribute to an obesity-prone phenotype with increased age. We here discuss the hypothesis that the age-related loss of brown adipocyte regenerative capacity is a result of dysfunctional stem/progenitor cells. The possible molecular mechanisms that lead to an age-related decline in brown adipogenic stem/progenitor cell function include cell-autonomous and external effects. General loss of mitochondrial biogenesis and function has repeatedly been linked to age-related perturbation of metabolic processes. We also discuss the possibility that alterations in neuronal control by the sympathetic nervous system may contribute to impaired regeneration and thermogenesis in aged brown adipocytes. Finally, age-related changes of endocrine signals have been proposed to exacerbate the loss of brown adipose tissue. In conclusion, age-induced impairment of brown adipogenic stem/progenitor cell function could contribute to the loss of brown adipocyte regeneration, thereby promoting the development of obesity and other metabolic disorders with age.

Publication types

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

MeSH terms

  • Adipocytes, Brown / pathology*
  • Adipocytes, Brown / physiology*
  • Adipogenesis
  • Adipose Tissue, Brown / pathology
  • Adipose Tissue, Brown / physiopathology
  • Adult
  • Adult Stem Cells / pathology
  • Adult Stem Cells / physiology
  • Aged
  • Aging / pathology*
  • Aging / physiology*
  • Animals
  • Atrophy
  • Endocrine Glands / physiopathology
  • Energy Metabolism
  • Female
  • Geriatrics
  • Humans
  • Male
  • Mesenchymal Stem Cells / pathology
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Middle Aged
  • Organelle Biogenesis
  • Regeneration
  • Sympathetic Nervous System / physiopathology
  • Thermogenesis