Comments on ‘The biology and functional morphology of Arctica islandica’ by Brian Morton, Marine Biology Research, 2011

Abstract

In a recent review, Morton (2011, ‘The biology and functional morphology of Arctica islandica (Bivalvia: Arcticidae) – A gerontophilic living fossil’, Marine Biology Research 7:540–53) provides a detailed description of the function of the anatomy of the long-lived Arctica islandica. In the abstract, Morton concludes that the indolent lifestyle and tissue antioxidant levels sustained into gerontocy predisposes it to negligible senescence and states stable tissue antioxidant levels may slow senescence and extend lifespan. While briefly reviewing only a sub-section of the literature on antioxidants in bivalves, Morton further states that high antioxidant capacities may explain the long lifespan of A. islandica. Recent research demonstrates that such statements are misleading or unsubstantiated. Genetic manipulations of antioxidant expression in a range of species and comparisons of antioxidant activities in longer-lived species compared to shorter-lived relatives produces inconsistent results, but more often elevated antioxidants levels rarely extend lifespan The lack of a clear relationship limits our ability to infer longevity consequences from measures of antioxidant status. In addition, it is outlined why the oxidative stress theory of ageing is severely questioned, if not refuted, and antioxidant capacities of long-lived bivalves do not show such a clear pattern as indicated.

Keywords:

• Antioxidants
• Arctica islandica
• free radical theory of ageing
• longevity

Published in collaboration with the University of Bergen and the Institute of Marine Research, Norway, and the Marine Biological Laboratory, University of Copenhagen, Denmark

In a recent review, Morton (2011) describes the function of the anatomy of the long-lived Arctica islandica (Linnaeus, 1767). In the abstract, Morton (2011) concludes that the indolent lifestyle and antioxidant levels sustained into gerontocy predisposes it to negligible senescence and states stable antioxidant capacities (referring to the stable catalase, citrate synthase activity and glutathione concentrations (Abele et al. 2008)) may slow senescence and extend lifespan. While briefly reviewing a sub-section of the literature on antioxidants in bivalves, Morton (2011) further states that high antioxidant capacities (elevated catalase reported by Abele et al. 2008) may explain the long lifespan of A. islandica. Recent research demonstrates that such statements are misleading or unsubstantiated. In this response, it is outlined why the free radical theory of ageing is severely questioned, if not refuted; that elevated antioxidants levels have rarely been observed to extend lifespan; and antioxidant capacities of long-lived bivalves do not show such a clear pattern as indicated.

The modified free radical theory of ageing (Harman 1956), now the oxidative stress theory of ageing, essentially proposes the imbalance between pro-oxidants and antioxidants leads to an accumulation of oxidative damage with age resulting in a progressive loss in function. Early genetic manipulations upregulating antioxidants extended lifespan and provided strong support for this theory (Sohal & Weindruch 1996). However, retrospective analyses of these studies suggest that suboptimal conditions and/or the use of short-lived, unhealthy stocks may have been a contributing factor (Sohal et al. 2002). In fact, increasing the expression of genes for cellular antioxidants (e.g. glutathione) and antioxidant enzymes (e.g. superoxide dismutase (SOD) and catalase) in a range of organisms has consistently failed to increase lifespan (Mockett et al. 1999, 2003; Huang et al. 2000; Doonan et al. 2008). In addition, ‘knocking out’ the gene for cellular antioxidants (e.g. glutathione) and antioxidant enzymes (e.g. SOD) did not result in reduced lifespan in other species (Doonan et al. 2008; Salmon et al. 2009).

Pérez et al. (2009) reviewed their own research and the literature pertaining to mice and concluded that the data demonstrated that almost all alterations in the antioxidant system have no effect on lifespan. Similarly, Buffenstein et al. (2008) concluded that genetic manipulations altering antioxidant expression do not necessarily show an impact on lifespan and the available data do not support the premise that superior antioxidant defence contributes to species longevity.

Comparisons of antioxidant activities in longer-lived species compared to shorter-lived relatives produces inconsistent results. In rodents (Buffenstein et al. 2008: measuring or reviewing data on catalase, SOD and methionine sulfoxide reductase) and birds (Cohen et al. 2008: measuring uric acid, carotenoids, vitamin E and total antioxidant capacities), no predictable relationships between antioxidant levels and longevity is observed. Similar inconsistencies are observed in bivalves; Abele et al. (2009) report elevated catalase levels compared to the shorter-lived bivalves while Ungvari et al. (2011) found no difference in total or specific antioxidant capacities between long-lived A. islandica and shorter-lived Mercenaria mercenaria. Correspondingly, observations of SOD activity in the long-lived Margaritifera margaritifera (Fernández et al. 2009) were very similar to those in the shorter-lived Mytilus edulis (Winston et al. 1990). The lack of a clear relationship limits our ability to infer longevity consequences from measures of antioxidant status (Buttemer et al. 2010).

Maintenance of stable antioxidant levels observed in A. islandica (Abele et al. 2008; Ungvari et al. 2011) and other longevous species (e.g. naked mole rats; Andziak et al. 2005) provide evidence that ageing rates are retarded in these long-lived species rather than a causative factor in retarded ageing. Morton (2011) seems to have confused causation and correlation. Do stable antioxidants retard ageing, or does retarded ageing cause stable antioxidants? While age-associated changes in antioxidant activities of mice are enzyme-specific (manganese superoxide dismutase increased while cellular glutathione peroxidase and catalase decreased), generation rates of superoxide and hydrogen peroxide have been shown to increase with age in shorter-lived species (e.g. mice; Sohal et al. 1994).

In light of the research outlined above, recent reviews have questioned whether the oxidative stress theory of ageing is dead (Gems & Doonan 2009; Pérez et al. 2009; Salmon et al. 2009), or even that it is now reasonable to consider the theory refuted (Lapointe & Hekimi 2010). Since Abele et al. (2009) reviewed antioxidant capacities in bivalves, the field has considerably advanced, and if not dead, the role of oxidative stress in ageing is now severely questioned. One cannot take a component of the oxidative stress system in a species and make simplistic assumptions about its role in attenuated ageing, and there is no conclusive evidence that antioxidants play a significant role in determining lifespan in bivalves. Future research into the mechanisms responsible for the exceptional lifespan of bivalves should therefore also target alternative theories of ageing, as it is time to start thinking about ageing in new ways (Gems & Doonan 2009).

Editorial responsibility: Tom Fenchel

Notes

Published in collaboration with the University of Bergen and the Institute of Marine Research, Norway, and the Marine Biological Laboratory, University of Copenhagen, Denmark