An Evolutionary Programmed Aging Viewpoint

Josh Mitteldorf blogs fairly regularly on the topic of aging and longevity science. I believe that he and I are on much the same page when it comes to the necessity for greater funding and more rapid progress towards therapies to treat degenerative aging, and the plausibility of achieving radical life extension through medical technology. When it comes to the details of how to proceed, however, we are at opposite ends of the pool. Based on my reading of the field, I see aging as accumulated damage and the reactions to that damage, which means that SENS-like research focused on damage repair is the way to create rejuvenation. Mitteldorf, on the other hand, sees aging as a genetic program that creates damage. In his view damage repair will be ineffectual, and the research community should focus on adjusting the operation of metabolism such that its epigenetic patterns are restored to youthful levels - reversing the program, in other words. So he is in favor of the expansion of programs such as work on drugs to change TOR signaling, for example.

The types of life extension research that the two of us back couldn't be more different, and the predicted outcomes stand in opposition to one another. To a programmed aging advocate damage repair is a slow road to nowhere, while the aging as damage camp in turn see manipulation of metabolism and epigenetic patterns as a slow road to marginal treatments. Interestingly, the mainstream of the research community largely holds an aging as damage consensus, but they also largely work on ways to slow aging through metabolic manipulation, rather than aiming for damage repair. This I blame on the costly and extensive regulations associated with medical research and clinical application of medicine: if your work isn't a drug that can be targeted to a specific named disease, then getting it approved for use will be somewhere between an exceedingly expensive uphill battle and impossible. This reality is recognized and percolates back up the research chain to make it very hard to raise funding for even early stage research into anything that is new, radical, and different.

In any case, I see the programmed aging view as interesting but wrong. Everyone in the community, whether hypothesizing programmed aging or aging as damage, largely agrees on the facts in evidence, the differences between old and young tissue and other data. The interpretation of those facts is where the action is. Mitteldorf's views are similar in some ways but also a little different from those of the Russian gerontology community I've pointed out in past posts, and so seem worth reading through.

The Selfish Gene vs Multi-level Selection: Aging Doesn't Fit

Genes are evolved to promote their own replication, and also copies of themselves that exist in relatives. In the 1970s, the theory was extended by George Price to deal rigorously with groups that may or may not be related. This is now known as multi-level selection (MLS). There is an ongoing dialog in the evolutionary community about whether MLS is significant in nature, which is still the minority view. The majority continues to hold that everything should be explainable in terms of the selfish gene.

But aging cannot be explained by the selfish gene; and even with the considerably broader perspective of MLS, the evolution of aging remains problematic. What is missing from both systems is ecology. When species' interdependence is taken into account, it becomes possible to understand aging and many other cases where individuals sacrifice their own fitness to the community.

The Selfish Gene can't explain aging - but neither can Multi-level Selection

Last week, I discussed the gene-eyed view of evolution that came to dominate evolutionary theory of the 20th century. In the 1960s, this view hardened into a dogma, and provoked a reaction, in recognition of the many cooperative networks in nature that are difficult to explain in terms of "kin selection," the only recourse of the Selfish Gene.

I continue [here] with the science of multilevel selection (MLS), and talk about why aging is a tough nut to crack. Clearly the selfish gene paradigm is inadequate to explain aging. MLS provides a formal test for deciding whether a given trait can evolve via group selection, and according to these criteria, aging should not be able to evolve.

Where do we go from here? What is missing from both systems is ecology. When species' interdependence is taken into account, it becomes possible to understand aging and many other cases where individuals sacrifice their own fitness to the community.