The issue of body size and lifespan is a fascinating topic in biology. It’s strange that across species, at least in mammals, large bodied animals live longer than small sized animals . For example, elephants live a lot longer than mice. The theory is that bigger animals have slower metabolisms than small animals, and that faster metabolisms result in more accumulation of free radicals that damage tissue and DNA . But this doesn’t always hold for all animals and the “rate of living” theory is not widely accepted. What we cannot clearly understand remains fascinating.
But now if we look within a given species, lifespan and body size are inversely correlated. This is definitively the case for dogs and mice, and it has been proposed that this is the case for humans too . Why would this be? A possible explanation is that larger dogs (or mice, or people) grow faster than their smaller counterparts because they reach a larger size in more or less the same time, and that faster growth could be correlated with higher cancer rates .
We do not have a clear understanding of why growing faster leads to accelerated aging. But it seems that it is an accelerated rate of aging, or senescence, that causes larger dogs to have a shorter lifespan than little dogs.
The figure is from : Ageing: It’s a Dog’s Life. The data is from 32 breeds. Note that the inverse correlation is pretty good, however some large dog breeds, at around 40 to 50 kg, live 12 or 13 years in average while some other dog breeds of equal body size live only 8 or 9 years in average. This is due to dogs being a special case as they were artificially bred by humans to select for looks or behavior and not necessarily health, and that considerable inbreeding was necessary to produce “purebred” dogs. For example, boxers are big dogs, but their higher cancer rates may result in a shorter lifespan. However, the really giant breeds all consistently live 8–9 years on average. So there is something going on besides simple breeding quirks that led to bad genetics and ill health. Something more general.
A few years ago, a large study was published  using mortality data from thousands of dogs across 74 breeds, testing 3 hypotheses: Large dogs may die younger than small dogs because of (1) an earlier onset of senescence, (2) a higher minimum mortality hazard or (3) an increased rate of aging. The conclusion from their study is that aging starts more or less at the same age in small and large breeds, but large breeds age faster. We do not have a clear understanding of the underlying mechanism for faster aging in dogs. It seems that when we selected for large body size, we selected for faster aging as well. But we do not know all the genetic components of this. We know that there are at least 3 genes that determine large body size in dogs, IRS4 and IGSF1, involved in thyroid hormone pathways which affect growth, and ACSL4, involved in muscle growth, and back fat thickness . But how this accelerates aging is still speculation. More studies are needed, but dogs seem to be a great model to study the evolution of body size and its relationship to aging.
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