Role of sphingolipids in senescence: implication in aging and age-related diseases

J Clin Invest. 2018 Jul 2;128(7):2702-2712. doi: 10.1172/JCI97949. Epub 2018 Jul 2.

Abstract

Aging is defined as the progressive deterioration of physiological function with age. Incidence of many pathologies increases with age, including neurological and cardiovascular diseases and cancer. Aging tissues become less adaptable and renewable, and cells undergo senescence, a process by which they "irreversibly" stop dividing. Senescence has been shown to serve as a tumor suppression mechanism with clear desirable effects. However, senescence also has deleterious consequences, especially for cardiovascular, metabolic, and immune systems. Sphingolipids are a major class of lipids that regulate cell biology, owing to their structural and bioactive properties and diversity. Their involvement in the regulation of aging and senescence has been demonstrated and studied in multiple organisms and cell types, especially that of ceramide and sphingosine-1-phosphate; ceramide induces cellular senescence and sphingosine-1-phosphate delays it. These discoveries could be very useful in the future to understand aging mechanisms and improve therapeutic interventions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Aging / metabolism*
  • Aging / pathology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Animals
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Biomarkers / metabolism
  • Cellular Senescence / physiology
  • Ceramides / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Humans
  • Immune System / metabolism
  • Immune System / pathology
  • Lysophospholipids / metabolism
  • Metabolic Networks and Pathways
  • Models, Biological
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Sphingolipids / metabolism*
  • Sphingosine / analogs & derivatives
  • Sphingosine / metabolism

Substances

  • Biomarkers
  • Ceramides
  • Lysophospholipids
  • Sphingolipids
  • sphingosine 1-phosphate
  • Sphingosine