Superoxide dismutase is dispensable for normal animal lifespan

Abstract

Reactive oxygen species (ROS) are toxic oxygen-containing molecules that can damage multiple components of the cell and have been proposed to be the primary cause of aging. The antioxidant enzyme superoxide dismutase (SOD) is the only eukaryotic enzyme capable of detoxifying superoxide, one type of ROS. The fact that SOD is present in all aerobic organisms raises the question as to whether SOD is absolutely required for animal life and whether the loss of SOD activity will result in decreased lifespan. Here we use the genetic model organism Caenorhabditis elegans to generate an animal that completely lacks SOD activity ( sod-12345 worms). We show that sod-12345 worms are viable and exhibit a normal lifespan, despite markedly increased sensitivity to multiple stresses. This is in stark contrast to what is observed in other genetic model organisms where the loss of a single sod gene can result in severely decreased survival. Investigating the mechanism underlying the normal lifespan of sod-12345 worms reveals that their longevity results from a balance between the prosurvival signaling and the toxicity of superoxide. Overall, our results demonstrate that SOD activity is dispensable for normal animal lifespan but is required to survive acute stresses. Moreover, our findings indicate that maintaining normal stress resistance is not crucial to the rate of aging.

Antioxidants reveal an inverted U‐shaped dose‐response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans

“…The range of concentrations for NAC and VitC was chosen based on previous work. PQ however was simply dissolved in water and was only tested at one concentration (0.1 m m ), as the inverted U‐shaped dose dependency of its lifespan‐lengthening effects is already well documented (Van Raamsdonk & Hekimi, 2012). Under conditions used, NAC, RSV, and PQ were capable of increasing wild‐type lifespan in a dose‐dependent manner (Fig.…”

“…The placement of the dose–response relationship along the two axes (lifespan and PQ concentration) depends on the genotype tested (Hwang et al ., 2014). These observations suggest that there is also an inverted U‐shaped relationship between mtROS levels and lifespan (Van Raamsdonk & Hekimi, 2012). This model potentially explains various observations.…”

“…However, recent findings suggest that superoxide detoxification by SOD enzymes is not involved in the aging process. Indeed, knocking out all five C. elegans SODs in the same strain (abbreviated sod‐12345 ) does not shorten lifespan despite elevated oxidative stress (Yang & Hekimi, 2010a; Van Raamsdonk & Hekimi, 2012). …”

“…Treatment of wild‐type worms (N2) with PQ results in an inverted U‐shaped dose–response relationship with a maximal lifespan‐lengthening effect at 0.1 m m (Yang & Hekimi, 2010a; Van Raamsdonk & Hekimi, 2012). The placement of the dose–response relationship along the two axes (lifespan and PQ concentration) depends on the genotype tested (Hwang et al ., 2014).…”

“…This model potentially explains various observations. For example, treatment of isp‐1(qm150) and nuo‐6(qm200) with antioxidants leads to a shortening of their extended lifespans (Yang & Hekimi, 2010a; Van Raamsdonk & Hekimi, 2012). …”