The 400 year old heart: association of increased resistance to oxidative stress with extreme longevity

To test whether ROS production and resistance to oxidative stress might be causally involved in enhanced longevity, we compared H2O2 and O2.‐ generation, resistance to oxidative stress and antioxidant defenses in the ocean quahog Arctica islandica (lifespan: >400 years), and the shorter lived hard clam, Mercenaria mercenaria (lifespan: ~60 years). We found that extreme longevity in A. islandica is associated with an attenuated cellular ROS production. Resistance to aging at the organismal level is often reflected in resistance to oxidative stressors at the cellular level. Following exposure to the oxidative stressor tert‐butyl hydroperoxide (TBHP) we observed not only an association between longevity and resistance to oxidative stress‐induced mortality, but also marked resistance to oxidative stress–induced cell death in the longer‐living bivalves. Contrary to the predictions of the oxidative stress hypothesis of aging we observed not only that A. islandica exhibited neither greater antioxidant capacities nor specific activities than in M. mercenaria, but also did not exhibit a more pronounced homeostatic antioxidant response following TBHP exposure. Our findings demonstrate an association between longevity and resistance to oxidative stress–induced cell death in A. islandica, in accordance with the oxidative stress hypothesis of aging. (Funding: ADA, AFAR, NIH).