Fight Aging!

There are many comparatively simple genetic alterations that enable animals of various different laboratory species to live between 10% to 60% longer. These are changes to the operation of metabolism: perhaps more autophagy, perhaps less fat tissue, perhaps fat tissue that behaves slightly less maliciously, perhaps a more resilient immune system, and so forth. The list is long and getting longer with each passing year as researchers continue to investigate the genetics of aging and longevity.

Here is a question: if all these changes are so simple, just minor genetic alterations, how is it that evolution failed to get there first? Why is it that researchers can alter the mouse genome in many different ways to extend the lives of laboratory mice? Why is the local optimal evolved state of the modern mouse short-lived in comparison to a great many close, easily-reached neighboring states?

The answer to these questions is that additional longevity is only one of many possible advantages to be obtained in evolutionary competition, and probably not a terribly good advantage in the grand scheme of things. In theory, and if individuals successfully evade natural hazards and predators, a longer life span means that a lineage can outbreed its competitors over time. Judging by the fact that very few species are unusually long-lived in comparison to their peers, however, we might conclude that longevity is only rarely more beneficial than other strategies for evolutionary success.

When researchers examine long-lived mutant mice, worms, and other short-lived species, they see signs that these lineages would be outmatched in the wild. Minor genetic changes to enhance longevity, even ones such as improved cellular maintenance that seem wholly beneficial, are not free. They come with attached costs in terms of success in the only game that matters over evolutionary time, which is the competition to propagate copies of your genome.

Hormesis and longevity with tannins: Free of charge or cost-intensive?

Hormetic lifespan extension is, for obvious reasons, beneficial to an individual. But is this effect really cost-neutral? To answer this question, four tannic polyphenols were tested on the nematode Caenorhabditis elegans. All were able to extend the lifespan, but only some in a hormetic fashion.

Additional life trait variables including stress resistance, reproductive behavior, growth, and physical fitness were observed during the exposure to the most life extending concentrations. These traits represent the quality of life and the population fitness, being the most important parameters of a hormetic treatment besides lifespan. Indeed, it emerged that each life-extension is accompanied by a constraining effect in at least one other endpoint, for example growth, mobility, stress resistance, or reproduction. Thus, in this context, longevity could not be considered to be attained for free and therefore it is likely that other hormetic benefits may also incur cost-intensive and unpredictable side-effects.

Laboratory selection for increased longevity in Drosophila melanogaster reduces field performance

Drosophila melanogaster is frequently used in ageing studies to elucidate which mechanisms determine the onset and progress of senescence. Lines selected for increased longevity have often been shown to perform as well as or superior to control lines in life history, stress resistance and behavioural traits when tested in the laboratory. Functional senescence in longevity selected lines has also been shown to occur at a slower rate.

However, it is known that performance in a controlled laboratory setting is not necessarily representative of performance in nature. In this study the effect of ageing, environmental temperature and longevity selection on performance in the field was tested. Flies from longevity selected and control lines of different ages (2, 5, 10 and 15 days) were released in an environment free of natural food sources. Control flies were tested at low, intermediate and high temperatures, while longevity selected flies were tested at the intermediate temperature only. The ability of flies to locate and reach a food source was tested.

Flies of intermediate age were generally better at locating resources than both younger and older flies, where hot and cold environments accelerate the senescent decline in performance. Control lines were better able to locate a resource compared to longevity selected lines of the same age, suggesting longevity comes at a cost in early life field fitness, supporting the antagonistic pleiotropy theory of ageing.

If you are a member of a species with access to advanced medical technology, none of this much matters any more, of course. The future of longevity under those circumstances is determined by progress in technology rather than evolution: natural selection just sets the scene, and ensures that we are all dissatisfied with the hand we have been dealt.