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.

Source:
https://www.fightaging.org/archives/2013/08/the-cost-of-living-longer-even-in-good-health.php

I had somehow missed this event from earlier in the year, a provocative (by mainstream standards) ad campaign mounted by a portion of the insurance industry: "The First Person To Live To 150 Is Alive Today." I take the existence of such a campaign as a sign of progress in ongoing efforts to spread the twofold message that (a) much longer lives are possible in the future, and (b) it is necessary to support the research process in order to make this happen soon enough to matter to you and I. Most of the children born today in wealthier parts of the world will have the opportunity to live for centuries at the very least, but the odds of people presently in mid-life are far more dependent on the pace of medical progress, and whether or not the right research strategies are nurtured.

By the side of an expressway the other afternoon, I saw a billboard paid for by Prudential, the big insurance and financial-services company. The message, in letters large enough that no motorist zipping by could miss them: "The First Person To Live To 150 Is Alive Today."

For centuries, scientists have been debating theories about just how long, with proper health care and judicious personal habits, the human lifespan can extend. In recent years, the 150 number has been up for discussion. Some have scoffed at that prospect, but insurance-company actuaries and retirement-planning accountants are not known for wacky practical jokes - they are as somber-eyed as funeral directors as they calculate just how big a risk they run while writing policies for their customers of various ages - so the sight of that Prudential billboard was a little jarring.

I contacted Prudential's corporate headquarters, and the company forwarded to me a table of federal statistics showing the lengthening average lifespans in the U.S. over the past 80 or so years. In 1930, the average life expectancy (measured at birth) of Americans was 59.7 years. By 1940, it had grown to 62.9. 1950: 68.2. 1960: 69.7. 1970: 70.8. 1980: 73.7 1990: 75.4. 2000: 77. 2010: 78.7.

Whether infants born today are entering a world in which 150th birthdays will eventually become if not common then at least possible, the thought raises separate issues for insurance and financial-planning firms than it does for the rest of us. For those companies, the prospect provides marketing opportunities. But for everyone else, it prompts the vexing question: Would you really want to live that long?

Link: http://www.cnn.com/2013/06/23/opinion/greene-living-to-150

Source:
https://www.fightaging.org/archives/2013/08/signs-of-progress-insurers-talk-of-radical-life-extension.php

The interaction between genes, metabolism, and natural variations in longevity is an enormously complex space. This complexity is why efforts to slow aging by altering metabolism are doomed to be a very slow, very expensive undertaking, one which is unlikely to produce meaningful results within the next few decades. It will be much easier to instead identify the forms of damage that cause aging and periodically repair them without trying to otherwise change our genes or metabolic processes. We know the metabolism we have when young works just fine, so the focus of longevity science should be on reverting the limited set of changes in and around cells that differentiate old tissues from young tissues.

Here is a good short summary of the current state of knowledge of genetics and longevity, illustrating that researchers are really only just at the outset of a very long process of obtaining a full or at least actionable understanding:

Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25%. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages.

Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences.

GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity.

Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and rare alleles, with impeccable control for population stratification and consideration of non-genetic factors such as environment.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23925498

Source:
https://www.fightaging.org/archives/2013/08/the-current-state-of-knowledge-of-genetics-and-longevity.php