Target of rapamycin activation predicts lifespan in fruit flies

Cell Cycle. 2015;14(18):2949-58. doi: 10.1080/15384101.2015.1071745.

Abstract

Aging and age-related diseases are one of the most important health issues that the world will confront during the 21(st) century. Only by understanding the proximal causes will we be able to find treatments to reduce or delay the onset of degenerative diseases associated with aging. Currently, the prevalent paradigm in the field is the accumulation of damage. However, a new theory that proposes an alternative explanation is gaining momentum. The hyperfunction theory proposes that aging is not a consequence of a wear and tear process, but a result of the continuation of developmental programs during adulthood. Here we use Drosophila melanogaster, where evidence supporting both paradigms has been reported, to identify which parameters that have been previously related with lifespan best predict the rate of aging in wild type flies cultured at different temperatures. We find that mitochondrial function and mitochondrial reactive oxygen species (mtROS) generation correlates with metabolic rate, but not with the rate of aging. Importantly, we find that activation of nutrient sensing pathways (i.e. insulin-PI3K/Target of rapamycin (Tor) pathway) correlates with lifespan, but not with metabolic rate. Our results, dissociate metabolic rate and lifespan in wild type flies and instead link nutrient sensing signaling with longevity as predicted by the hyperfunction theory.

Keywords: Target of rapamycin; aging; damage theories; hyperfunction; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / physiology*
  • Energy Metabolism
  • Longevity
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Sirolimus / pharmacology*

Substances

  • Reactive Oxygen Species
  • Sirolimus