Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress.
The accumulation of free radical damage to an organism over its lifespan can cause premature aging and disease including cancer, atherosclerosis and neurodegenerative disorders. The well-conserved Rheb-Target-of-rapamycin (TOR)-S6-kinase (S6K) signaling pathway regulates several cellular processes and has been shown to influence lifespan and diseases such as cancer and neurodegenerative disorders. Using adult Drosophila, we describe for the first time in metazoans that TOR activity can influence the stress response. We find that mildly increasing systemic Rheb-TOR-S6K signaling sensitizes the whole organism to oxidative stress and promotes senescence of locomotor activity with age. Furthermore, we find that S6K is required for increased Rheb-TOR signaling to sensitize the whole organism to oxidative stress and promote the senescence of locomotor activity. Interestingly, we also find that increasing Rheb-TOR signaling in muscle can increase the sensitivity of adults to oxidative stress. These data imply that pathological situations that increase TOR activity might perturb the ability of the whole organism to cope with stress causing disease progression and aging.
Patel
Parthive H
PH
Molecular Biology Institute, Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095-1489, USA.
Tamanoi
Fuyuhiko
F
D000375:Aging / Q000502:physiology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005216:Fat Body / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009132:Muscles / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases; D000076205:Ras Homolog Enriched in Brain Protein; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013217:Starvation; D058570:TOR Serine-Threonine Kinases
D029721:Drosophila Proteins; D020559:Monomeric GTP-Binding Proteins; D009479:Neuropeptides; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D000076205:Ras Homolog Enriched in Brain Protein; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; C490212:Rheb protein, Drosophila; C416303:target of rapamycin protein, Drosophila