Thrombospondin-1 in maladaptive aging responses: a concept whose time has come

Am J Physiol Cell Physiol. 2020 Jul 1;319(1):C45-C63. doi: 10.1152/ajpcell.00089.2020. Epub 2020 May 6.

Abstract

Numerous age-dependent alterations at the molecular, cellular, tissue and organ systems levels underlie the pathophysiology of aging. Herein, the focus is upon the secreted protein thrombospondin-1 (TSP1) as a promoter of aging and age-related diseases. TSP1 has several physiological functions in youth, including promoting neural synapse formation, mediating responses to ischemic and genotoxic stress, minimizing hemorrhage, limiting angiogenesis, and supporting wound healing. These acute functions of TSP1 generally require only transient expression of the protein. However, accumulating basic and clinical data reinforce the view that chronic diseases of aging are associated with accumulation of TSP1 in the extracellular matrix, which is a significant maladaptive contributor to the aging process. Identification of the relevant cell types that chronically produce and respond to TSP1 and the molecular mechanisms that mediate the resulting maladaptive responses could direct the development of therapeutic agents to delay or revert age-associated maladies.

Keywords: CD47; aging; cardiovascular and metabolic disease; self-renewal; senescence; thrombospondin-1.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Aging / genetics*
  • Aging / metabolism*
  • Animals
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / therapy
  • DNA Damage / physiology
  • Humans
  • Musculoskeletal Diseases / genetics
  • Musculoskeletal Diseases / metabolism
  • Musculoskeletal Diseases / therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Signal Transduction / physiology
  • Thrombospondin 1 / antagonists & inhibitors
  • Thrombospondin 1 / biosynthesis*
  • Thrombospondin 1 / genetics*
  • Wound Healing / physiology

Substances

  • Thrombospondin 1