TOR Signaling Pathway in Cardiac Aging and Heart Failure

Biomolecules. 2021 Jan 27;11(2):168. doi: 10.3390/biom11020168.

Abstract

Mechanistic Target of Rapamycin (mTOR) signaling is a key regulator of cellular metabolism, integrating nutrient sensing with cell growth. Over the past two decades, studies on the mTOR pathway have revealed that mTOR complex 1 controls life span, health span, and aging by modulating key cellular processes such as protein synthesis, autophagy, and mitochondrial function, mainly through its downstream substrates. Thus, the mTOR pathway regulates both physiological and pathological processes in the heart from embryonic cardiovascular development to maintenance of cardiac homeostasis in postnatal life. In this regard, the dysregulation of mTOR signaling has been linked to many age-related pathologies, including heart failure and age-related cardiac dysfunction. In this review, we highlight recent advances of the impact of mTOR complex 1 pathway and its regulators on aging and, more specifically, cardiac aging and heart failure.

Keywords: aging; caloric restriction; cardiac aging; heart failure; mTOR; rapamycin.

Publication types

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

MeSH terms

  • Aging / metabolism*
  • Animals
  • Autophagy*
  • Caloric Restriction*
  • Heart / physiopathology
  • Heart Failure / metabolism*
  • Homeostasis
  • Humans
  • Longevity
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mitochondria / metabolism
  • Proteins / metabolism
  • Signal Transduction*
  • Sirolimus / chemistry
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Proteins
  • MTOR protein, human
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • Sirolimus