title: Aspirin inhibits oxidant stress, reduces age-associated functional declines, and extends lifespan of Caenorhabditis elegans.
abstract: OBJECTIVE
  Oxidative stress and inflammation are leading risk factors for age-associated functional declines. We assessed aspirin effects on endogenous oxidative-stress levels, lifespan, and age-related functional declines, in the nematode Caenorhabditis elegans.
  
  
  RESULTS
  Both aspirin and its salicylate moiety, at nontoxic concentrations (0.5-1 mM), attenuated endogenous levels of reactive oxygen species (p<0.001), and upregulated antioxidant genes encoding superoxide dismutases (especially sod-3, p<0.001), catalases (especially ctl-2, p<0.0001), and two glutathione-S-transferases (gst-4 and gst-10; each p<0.005). Aspirin, and to a lesser degree salicylate, improved survival of hydrogen peroxide, and in the absence of exogenous stress aspirin extended lifespan by 21%-23% (each p<10(-9)), while salicylate added 14% (p<10(-6)). Aspirin and salicylate delayed age-dependent declines in motility and pharyngeal pumping (each p<0.005), and decreased intracellular protein aggregation (p<0.0001)-all established markers of physiological aging-consistent with slowing of the aging process. Aspirin fails to improve stress resistance or lifespan in nematodes lacking DAF-16, implying that it acts through this FOXO transcription factor.
  
  
  METHODS
  Studies in mice and humans suggest that aspirin may protect against multiple age-associated diseases by reducing all-cause mortality. We now demonstrate that aspirin markedly slows many measures of aging in the nematode.
  
  
  CONCLUSIONS
  Aspirin treatment is associated with diminished endogenous oxidant stress and enhanced resistance to exogenous peroxide, both likely mediated by activation of antioxidant defenses. Our evidence indicates that aspirin attenuates insulin-like signaling, thus protecting against oxidative stress, postponing age-associated functional declines and extending C. elegans lifespan under benign conditions.
authors.affiliation: Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA. AyyadevaraSrinivas@uams.edu
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ayyadevara
authors.forename: Puneet
authors.initials: P
authors.lastname: Bharill
authors.forename: Abhijit
authors.initials: A
authors.lastname: Dandapat
authors.forename: Changping
authors.initials: C
authors.lastname: Hu
authors.forename: Magomed
authors.initials: M
authors.lastname: Khaidakov
authors.forename: Sona
authors.initials: S
authors.lastname: Mitra
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Shmookler Reis
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008017:Life Expectancy; D008124:Locomotion; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D001241:Aspirin