Searching for sources of negligible senescence

Some species appear not to age, in the sense that they become no more likely to die as time passes — take, for example, Arctic quahogs, the longest-lived animals on record. How does such negligible senescence evolve?

This question can be broken down into two parts: First, under what pressures does the phenomenon of biological immortality evolve? (We’ve already discussed examples of how competition for space between young animals and either sessile adults or older colonies could trigger a sort of “arms race” in which age-related decline could be eliminated altogether; we’ve also considered situations in which quirks of reproductive life history can strengthen selection on late life and thereby drastically curtail age-related decline.) Second, what are the mechanisms of negligible senescence, i.e., what is different about the cells and tissues (or DNA, or lipids, or…) of long-lived organisms that might explain their longevity? Today we’re focusing on this second aspect of the question.

The first step in understanding the cellular and molecular basis of negligible senescence is to look at factors that are known to influence lifespan in other organisms — oxidized proteins, antioxidant defense systems, heat shock proteins — and see whether any of them show unusual patterns in long-lived animals. Ivanina et al. did just that with the mollusks, looking at aging-related molecular pathways in one clam and one oyster species. Unfortunately, shaking down the “usual suspects” didn’t reveal any hints:

Oxidative stress and expression of chaperones in aging mollusk
The mechanisms of aging are not well understood in animals with continuous growth such as fish, reptiles, amphibians and numerous invertebrates, including mollusks. We studied the effects of age on oxidative stress, cellular defense mechanisms (including two major antioxidant enzymes, superoxide dismutase (SOD) and catalase), and molecular chaperones in two mollusks — eastern oysters Crassostrea virginica and hard clams Mercenaria mercenaria. In order to detect the age-related changes in these parameters, correction for the effects of size was performed where appropriate to account for growth-related dilution. Fluorescent age pigments accumulated with age in both species. Protein carbonyls did not change with age or size indicating that they are not a good marker of aging in mollusks possibly due to the fast turnover and degradation of oxidized proteins in growing tissues. SOD did not show a compensatory increase with aging in either species, while catalase significantly decreased with age. Mitochondrial heat shock protein (HSP60) decreased with age in mollusks suggesting an age-related decline in mitochondrial chaperone protection. In contrast, changes in cytosolic chaperones were species-specific. HSP70 increased and HSP90 declined with age in clams, whereas in oysters HSP70 expression did not change, and HSP90 increased with aging.

In summary, nothing jumps out at you. The lack of accumulated carbonylated protein is intriguing, though I think this can be explained away by low oxygen use. There’s the usual age-related increase in lipofuscins, but beyond that there are no coherent directional changes in molecules of interest.

Granted, the authors didn’t study unusually long-lived species, instead looking at the changes that occur over the course of aging in species with more modest lifespans — and it may be that short-lived molluscs simply don’t possess the relevant features that confer negligible senescence on the Arctic quahog.

Another possibility is that molluscs are different enough from the more traditional (though less delicious) model organisms of biogerontology that our list of usual suspects won’t be useful — we might need a whole different lineup. Certainly, something is different about particular species of clams, trees, insects and possibly even rodents — it’s up to us to figure out what. The difference between “conventionally” aging species and negligibly senescent ones is one of quality rather than degree, and it may be that the mechanisms explaining (theoretically) infinite lifespans are wholly unrelated to those explaining finite ones. In order to reveal them, we may have to venture outside the warm glow of the lamppost.