Peter Lidsky and Mikolaj Ogrodnik Propose Different Tests of the Causes of Aging in a Joint Article
Peter Lidsky and Mikolaj Ogrodnik Propose Different Tests of the Causes of Aging in a Joint Article
On August 16, aging biologists Peter Lidsky and Mikolaj Ogrodnik published a joint article in which they answer the same 14 questions. The authors compare two explanations of why organisms age and propose observations that could help distinguish between them.
Ogrodnik starts with the gradual accumulation of damage to molecules and cellular structures. In this model, the rate of age-related functional decline depends on how quickly damage develops, how well the components of the organism resist it, whether the system has a reserve of similar components, and whether it can replace those that have been lost. He often interprets changes in cellular and organ function as responses to damage that has already accumulated.
Lidsky argues for a different framework. A limited lifespan may have become established through evolution as a set of inherited mechanisms, constituting a genetic program of aging. In his assessment, the pathogen control hypothesis is the most fully developed version of this framework. According to this hypothesis, chronic infections may have made old animals a source of risk to their relatives. Age-related changes in the immune system could therefore protect relatives from infection.
These causal models lead to different tests. Ogrodnik proposes measuring many types of damage simultaneously and deliberately reducing them in tissues that determine lifespan. Lidsky proposes comparing the genetic relatedness of animals with the genetic relatedness of the parasites that infect them. His hypothesis predicts that, in short-lived species, parasites found in related hosts will be more closely related genetically than they are in long-lived species. The hypothesis also predicts age-related changes in the immune system that harm the animal, as well as unusual susceptibility to infection in naked mole-rats.
On August 2, Lidsky had already called on the damage model to produce predictions that could be tested before an effective therapy was available. In the joint article, this criterion became the central point of disagreement. Lidsky considers the concept of damage too broad and asks for predictions that can be tested before aging can be eliminated. Ogrodnik responds that the pathogen control hypothesis must demonstrate links among infection burden, population structure, and longevity. It must also withstand experiments that manipulate infection or the immune response.
The 14 shared questions reduce the disagreement to observations that should distinguish the two accounts. One requires the measurement and removal of damage in tissues that affect lifespan. The other requires data linking infection, relatedness, and immunity. Such results could lead either author to revise his causal model of aging.