Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression

Cell Rep. 2013 Sep 12;4(5):913-20. doi: 10.1016/j.celrep.2013.07.030. Epub 2013 Aug 29.

Abstract

We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTOR(Δ/Δ)) alleles are viable but express mTOR at approximately 25% of wild-type levels. These animals demonstrate reduced mTORC1 and mTORC2 activity and exhibit an approximately 20% increase in median survival. While mTOR(Δ/Δ) mice are smaller than wild-type mice, these animals do not demonstrate any alterations in normalized food intake, glucose homeostasis, or metabolic rate. Consistent with their increased lifespan, mTOR(Δ/Δ) mice exhibited a reduction in a number of aging tissue biomarkers. Functional assessment suggested that, as mTOR(Δ/Δ) mice age, they exhibit a marked functional preservation in many, but not all, organ systems. Thus, in a mammalian model, while reducing mTOR expression markedly increases overall lifespan, it affects the age-dependent decline in tissue and organ function in a segmental fashion.

Publication types

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

MeSH terms

  • Aging / physiology
  • Animals
  • Female
  • Glucose / metabolism
  • Homeostasis
  • Longevity / physiology*
  • Male
  • Mammals
  • Mice
  • Signal Transduction
  • TOR Serine-Threonine Kinases / biosynthesis
  • TOR Serine-Threonine Kinases / deficiency*
  • TOR Serine-Threonine Kinases / genetics*

Substances

  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • Glucose