Fight Aging!

Yes, we're back to clams again: four hundred year old clams in this case. The ocean quahog, Arctica islandica, is a very long-lived bivalve that, like other unusually long-lived species, is attracting the attention of researchers. How is it that these animals manage to live so much longer than their near relatives? You'll find some background reading in the archives:

• Ageless Animals, Clam Edition
• Digging Into Clam Biochemistry
• Ageless Animals, the Pearl Mussel Edition

Researchers to date have focused on resistance to oxidative damage in quahogs, but the more research is done, the more ambiguous that picture becomes. It doesn't seem to be the case that we can simply point to very high levels of antioxidants or an aggressive antioxidant response that preserves cells from the accumulating damage caused by oxidative byproducts of metabolism. In many ways this parallels research into the biochemistry of the naked mole-rat: the initial focus on examining natural antioxidants gave way to the present view that their comparatively long life span depends on differences in the construction of their vulnerable cell membranes. They are better built in the places where it matters - their cells are buzzing with reactive oxidant compounds, but their resistant cell membranes shrug it off.

That may be the case for the quahog as well, but researchers aren't there yet. This recent paper manages to continue the present trend of muddying the waters:

We assess whether reactive oxygen species production and resistance to oxidative stress might be causally involved in the exceptional longevity exhibited by the ocean quahog Arctica islandica. We tested this hypothesis by comparing reactive oxygen species production, resistance to oxidative stress, antioxidant defenses, and protein damage elimination processes in long-lived A islandica with the shorter-lived hard clam, Mercenaria mercenaria. We compared baseline biochemical profiles, age-related changes, and responses to exposure to the oxidative stressor tert-butyl hydroperoxide (TBHP).

Our data support the premise that extreme longevity in A islandica is associated with an attenuated cellular reactive oxygen species production. The observation of reduced protein carbonyl concentration in A islandica gill tissue compared with M mercenaria suggests that reduced reactive oxygen species production in long-living bivalves is associated with lower levels of accumulated macromolecular damage, suggesting cellular redox homeostasis may determine life span. Resistance to aging at the organismal level is often reflected in resistance to oxidative stressors at the cellular level.

Following TBHP exposure, 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 some expectations from the oxidative stress hypothesis, we observed that A islandica exhibited neither greater antioxidant capacities nor specific activities than in M mercenaria nor a more pronounced homeostatic antioxidant response following TBHP exposure. The study also failed to provide support for the exceptional longevity of A islandica being associated with enhanced protein recycling.

Which is really saying little that is new and definitive - just better ruling out some of the options. The quahog could be producing fewer oxidants, or it could be efficiently mopping up oxidants at their source in the mitochondria due to a natural source of localized antioxidant compounds. In either case, that says nothing about how it or its cells might react to an externally provided and artificial source of oxidative stress like TBHP. Given the present pace of work, however, I'd expect that researchers will have developed a well-supported consensus explanation for the extreme longevity of this species and the naked-mole rat by the time 2020 rolls around.