Dying of old age: an unfounded myth? Rando paper, Box 2

I think you would be in a serious trouble if I ask you to explain the concrete death of an old, but otherwise healthy man in terms of the suspected biological processes of human ageing, like slowly accumulating mitochondrial and chromosomal mutations, oxidative stress, overall cell loss, intra- or extracelular junk molecules or whatever. In almost every definition of aging there is the actuarial, probabilistic and mechanism-blind term: “increased vulnerability to death” or “increased probability of dying” or something like that. But isn’t it useless and empty when we would like to explain the hows of ageing and dying? Now it is Thomas Rando’s turn for the second time in Pimm, author of a marvellous paper on stem cells and ageing. In the slightly philosophical, but definitely scientific Box 2, called “Dying of old age”, he explains (emphasis by me): “There is no compelling explanation for the cause of death in old but otherwise healthy humans, mice, worms or flies, or any other organism for that matter. The colloquial expression ‘dying of old age’ belies our knowledge of the biological basis of this event. Surely, the cessation of respiratory and circulatory functions results quickly in irreversible damage to vital organs; however, to insist that ageing of the heart or lungs is the cause of death only sidesteps the question. Examination of tissues of an old member of a species at the time of death will reveal stereotypical biological changes and perhaps even pathological changes that were only mildly symptomatic or even asymptomatic. Why, then, did this individual die? We can measure average and maximal lifespan in species, we can evaluate the effects of genetic, nutritional or pharmacological interventions that alter those indices, and we can correlate them with changes in tissue ageing. Yet no hypothesis has emerged that yields a useful definition of dying of old age in terms of cell and tissue biology.