title: The naked mole-rat response to oxidative stress: just deal with it.
abstract: CONCLUSIONS
  The oxidative stress theory of aging has been the most widely accepted theory of aging providing insights into why we age and die for over 50 years, despite mounting evidence from a multitude of species indicating that there is no direct relationship between reactive oxygen species (ROS) and longevity. Here we explore how different species, including the longest lived rodent, the naked mole-rat, have defied the most predominant aging theory.
  
  
  BACKGROUND
  In the case of extremely long-lived naked mole-rat, levels of ROS production are found to be similar to mice, antioxidant defenses unexceptional, and even under constitutive conditions, naked mole-rats combine a pro-oxidant intracellular milieu with high, steady state levels of oxidative damage. Clearly, naked mole-rats can tolerate this level of oxidative stress and must have mechanisms in place to prevent its translation into potentially lethal diseases.
  
  
  RESULTS
  In addition to the naked mole-rat, other species from across the phylogenetic spectrum and even certain mouse strains do not support this theory. Moreover, overexpressing or knocking down antioxidant levels alters levels of oxidative damage and even cancer incidence, but does not modulate lifespan.
  
  
  CONCLUSIONS
  Perhaps, it is not oxidative stress that modulates healthspan and longevity, but other cytoprotective mechanisms that allow animals to deal with high levels of oxidative damage and stress, and nevertheless live long, relatively healthy lifespans. Studying these mechanisms in uniquely long-lived species, like the naked mole-rat, may help us tease out the key contributors to aging and longevity.
authors.affiliation: 1 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
authors.forename: Kaitlyn N
authors.initials: KN
authors.lastname: Lewis
authors.forename: Blazej
authors.initials: B
authors.lastname: Andziak
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Rochelle
authors.initials: R
authors.lastname: Buffenstein
mesh_terms: D000375:Aging; D000818:Animals; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008136:Longevity; D019577:Mole Rats / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000502:physiology; D013045:Species Specificity
chemical_list: D010088:Oxidoreductases; D005978:Glutathione