“Happy families are all alike; every unhappy family is unhappy in its own way.” – Leo Tolstoy, Anna Karenina (1875)
The trouble with looking for one single root cause of aging is that – like everything else in biology – the lifespan of an organism is the result of a complex web of interactions. It’s a tapestry and pulling on any of a multitude of different strings can lead to its unraveling. I would like to propose the Anna Karenina Principle of Aging, which states that all short-lived species are short-lived in their own unique way. There are a multitude of different aspects of cell and tissue function that can ultimately go wrong, each of which can shorten the lifespan of an organism in its own unique way. Both fruit flies and worms age rapidly and die – they lose homeostasis (an internal biological balance) – but there’s no reason to believe that the aging process in either species has to be the same. There are just too many options for things to go wrong that no two sets of options have to resemble each other. The corollary of course is that all long-live species likely resemble each other in some key ways. So many ways to get it wrong, but only a few ways to get it right. (This can also be stated as the Flannery O’Connor Principle: “Everything that rises must converge.”) The evolution of long life can likely be viewed as convergent evolution where different long-lived species individually converge on the maintenance of long-term homeostasis. Most researchers who study aging do so by using short-lived species (Drosophila, Caenorhabditis elegans, Nothobranchius furzeri, etc.), largely because the organisms are small and easy to care for, and the experiments can be completed in a timely manner. I propose however that much more can potentially be learned from studying long-lived species. We need comprehensive comparative studies of the longest lived species on this planet, especially the things in the same class as ourselves – the mammals. We don’t just need to determine what the short-lived species are getting wrong (although that is valuable information); we need to determine what the longest-lived species are getting right.