Why Do Some Animals Live So Long? Sharks, Clams and the Biology of Ageing

Three general relationships hold across species and each has instructive failures. Larger animals live longer than smaller ones, which is why an elephant outlasts a mouse by fifty years, and the usual explanation involves metabolic rate, since small animals burn energy faster per gram. Animals with fewer predators live longer, because there is no evolutionary advantage in a body that lasts fifty years if something eats you at three, and this is the strongest single predictor. And animals that can escape predators by some other route, by flying, burrowing, carrying armour or being venomous, live far longer than their size predicts. Bats are the clearest case: a mouse-sized bat can live forty years against a mouse's three, and the difference is flight. Naked mole rats, which live underground in sealed colonies, reach over thirty years against a comparable rodent's four and show almost no increase in mortality rate with age, which is the textbook definition of negligible senescence.

Ageing is not one process, and the research literature has converged on a set of interacting mechanisms usually called the hallmarks of ageing:

• •Telomere shortening, since the protective caps on chromosome ends lose material at each division until a cell can no longer divide
• •Accumulated DNA damage, from radiation, chemistry and ordinary copying errors, which repair systems catch imperfectly
• •Senescent cells, which stop dividing but do not die and secrete inflammatory signals that damage their neighbours
• •Mitochondrial decline, which reduces the energy available to every cell
• •Loss of proteostasis, the accumulation of misfolded proteins that the disposal machinery can no longer clear
• •Stem cell exhaustion, so that worn tissue is replaced more slowly
• •Chronic low-grade inflammation, which rises with age and accelerates most of the others

The extreme cases each solve the problem differently. The Greenland shark grows about a centimetre a year in near-freezing water at very low metabolic rate, and its age was established only in 2016 by radiocarbon dating the proteins in its eye lenses, which form before birth and are never replaced. The ocean quahog clam is aged by counting annual bands in its shell, like tree rings, and shows exceptionally resistant cell membranes. Bowhead whales, at over two hundred years, carry duplicated copies of a gene involved in DNA repair and unusual variants in genes affecting cell cycle control. Elephants, which should get cancer constantly given their number of cells, carry twenty copies of the tumour suppressor gene TP53 against the human one, and their cells are unusually quick to self-destruct when damaged. Naked mole rats produce a high-molecular-mass version of a sugar polymer that appears to stop cells crowding into tumours. Among plants and simple animals the numbers are stranger still, with a bristlecone pine at nearly five thousand years, a glass sponge estimated at eleven thousand, and Hydra showing no measurable ageing at all because it replaces all of its cells continuously.

One animal appears to escape the problem entirely. Turritopsis dohrnii, a jellyfish a few millimetres across, can respond to starvation or injury by reverting from its adult medusa form to the juvenile polyp stage, a process called transdifferentiation in which its cells change type, and then developing again. In principle the cycle can repeat indefinitely, which is why it is called the immortal jellyfish. Two qualifications matter. It does this under stress rather than as routine, and in the wild it is eaten, so no individual actually persists forever. And its cells are far simpler and more plastic than a vertebrate's, so the trick does not obviously generalise. It is nonetheless a demonstration that ageing is not a law of physics but a set of biological arrangements that can, in at least one lineage, be run backwards.

The reason this research is funded generously is that ageing is the largest risk factor for cancer, heart disease, dementia and almost everything else that kills people in rich countries, so a treatment that slowed the process would address all of them at once rather than one at a time. The candidate interventions currently in or near human trials come mostly from this comparative work and from experiments in short-lived animals: caloric restriction and the drugs that mimic its effects, including rapamycin and metformin; senolytics, which selectively kill senescent cells and have extended healthy life in mice; and partial cellular reprogramming, which uses the genes that turn an adult cell into a stem cell, applied briefly, to reset markers of cell age without turning the cell into something else. None has yet been shown to extend human life, the record of promising ageing interventions failing in humans is long, and the honest summary is that we now understand why a bat outlives a mouse far better than we know what to do about it.

Lifespan tracks body size, but far more closely it tracks whether an animal can avoid being eaten, which is why bats, birds, tortoises and burrowing rodents outlive their size by decades. Ageing itself is a set of interacting failures including telomere loss, DNA damage, senescent cells, failing mitochondria and chronic inflammation. The record holders each solve one piece differently, with elephants carrying twenty copies of a tumour suppressor gene and bowhead whales extra DNA repair genes, and one small jellyfish can revert to its juvenile form under stress.