|Abstract:||Knowing the truth why we age is of enormous importance. Old dogmas in aging research are predominating the theories about the why and how we age. Such wrong dogmas inhibit and suppress the acquisition of new knowledge. Here we present an exposition of arguments against current theories about aging (Disposal Soma and Antagonistic Pleiotropy Theory) and the data with which sound theory should be compatible.|
Different life forms age with a wide range of paces (from days to centuries) and some appear not to age at all (negligible senescence) or were even classified as immortal (for instance species like Jellyfish and Hydra). During evolution nature invited different aging systems, longevity and immortality to specific biological niches. Many aging-systems invited were early developed during evolution. Most species adapted to their environment by developing such ancient aging-systems as these allowed to speed-up evolution and gave a huge selection advantage in a competitive changing world [Martins 2011].
Aging is in general considered as a unspectacular non-adaptive process [Kirkwood and Melov 2011]. Most gerontologists think aging did not evolve and is unrelated to development; the opposite viewpoint is more likely correct.
Scientist such as S. Melov and T. Kirkwood (where the former is rather conservative and the latter represents the peak of dogmatism!) have a very old-fashion view of the aging process which, besides having a cool name (“disposal soma theory”), is incompatible with the current existing data.
Recent evolutionary concepts, increasingly overwhelming publications in the literature as well as our own data argue in favour of another explanation why aging evolved and what its mechanisms is.
It is surprisingly that even old-school biogerontologists are beginning to admit “there is a programmed aging viewpoint that needs to be discussed” [Kirkwood and Melov 2011]. It is also surprising that they generally admit the relevance of many non-mammal species (while simultaneously denying it in some cases). Will wonders never cease?
However, many important facts and data relevant to understand the truth about why we really age were not mentioned at all! All things which they do not know or pretend to ignore (but true or false ignorance cannot be an everlasting shield for wrong ideas).
Therefore, in this correspondence we will clarify these issues in order to prevent that aging research will continue be such as disaster based on a totally wrong foundation as well as to prevent that forthcoming great scientist will not be blended with such incorrect frameworks and actually get the possibility to really solve aging.
The pacific salmon is a proper beginning for understanding aging. It is not a special exception. After reproduction this animal activates its aging systems and dies subsequently. Cases of acute phenoptosis were observed through the animal kingdom [Skulachev et al. 1999; Skulachev et al. 2003; Bradley et al. 1980; Skulachev, 1997; Skulachev, 1999, Comfort, 1979, Finch, 1990]. Australian dasyurid Dayurus hallucatus exhibit complete, ale die off after mating [Oakwood et al. 2001].
Cell death occurs through the execution of a genetically determined program: either apoptosis or necrosis. As programmed cell death operates in unicellular organisms such as bacteria and yeast, it indicates that a self-destructive programme even exists at an organism level. Indeed, altruistic death is actually very widespread phenomenon (called phenoptosis) in higher multicellular organisms such as plants and animals, including human, as it speeds up evolution via the stimulation of generation changes and consequently stimulation of biological evolution. Phenoptosis exerts the same role at a population level as apoptosis does at the level of an individual. Its goal is to protect the population from individuals potentially threatening population’s survival and reproductive potential. In the case of the pacific salmon it is sudden phenoptosis, while our aging is slow phenoptosis. Both phenomena are determined by supra-individual selection and are part of the same great category phenoptosis, but they are very different phenomena. In the former, the individual is sacrified for supra-individual interests and no one denies this. In the second case, the individual is sacrified for supra-individual interests but current theories consider this as impossible. Realistically, without phenoptotic phenomena the evolution of such a complex creature like human was never possible in the timeframe it happened!
“Nothing in evolution makes sense except in the light of population genetics.”
Apoptosis is accompanied with activation of MAP kinase cascade, accumulation of reactive oxygene species, release of cytochrome c from mitochondrial into cytoplasm as a consequence of opening the permeability transition pore in mitochondrial membrane and activation of caspases.
A natural signal molecule (pheromone) sex-specifically kills S. cerevisae cells [Severin and Hyman 2002]. Also bacteria undergo programmed cell death under certain conditions [Raff, 1998; Lewis, 2000].
Unicellular organisms commit altruistic suicide may be beneficial to the cell community as such a mechanism would improve the genetic fund of the community by eliminating the weak individuals.
Death is useful for evolution as it’s a mechanism for purifying the population form weak individual, and promoting succession of generations.
Even a small decline in fitness well result in a significant increase in death rate, therefore the evolutionary effects of aging in wild begins at relatively young ages [Goldsmith, 2004]. Indeed, the death rates in wild mammals increase beginning at puberty [Loison, 1999].
Deletion of Ste20 kinase prevents alpha-factor-induced death of a-type cells. Homologous of MAP kinase pathway is important in programmed cell death development in higher cells [Dan et al. 2001].
Pheromones also induce organism’s death program in mammals, such as the small marsupial Antechinus stuartii where the male uses pheromone to attract females and then to kill himself after run [Bradley et al. 1080].
Although senescence organisms are rarely seen in the wild, the mortality rate increase with chronological age in population in the wild [Libertini 2006; Libertini 2008]. If an older animal just exhibits a lower fitness conferred through aging, its probability to die and therefore free up resources for the next generation increases dramatically.
Comparing many species, all showing the increase of mortality phenomenon, the extrinsic or environmental mortality rates are inversely correlated with the Proportion of death due to intrinsic mortality [Figure: Inverse relationship between intrinsic and extrinsic mortality is incompatible with non-adaptive aging theories Adapted from (Ricklefs 1998)]. This does not at all mean that the variation of environmental mortality rates influences directly the rate of senescence within a single species.
With different models, Libertini and Travis [Libertini 1988; Travis 2004] proposed that territoriality (where kin selection is possible) or a spatially structured population are conditions that may make adaptive an age-related increment of mortality (commonly but imprecisely defined as aging).
Kirkwood and Melov admit that “There are theoretically, special circumstances in which a case for adaptive aging might exist” [Kirkwood and Melov 2011]. However, Kirkwood and Melov should consider some implications of adaptive (programmed) versus non-adaptive (non-programmed) interpretations of aging (for we prefer the precise description definition “increasing mortality with increasing chronological age” or “slow phenoptosis”). Kirkwood and Austad wrote: “The principal determinant in the evolution of longevity is predicted to be the level of extrinsic mortality…” [Kirkwood and Austad 2000], in short predicting that extrinsic mortality and intrinsic mortality should be directly related. The contrary (inverse relation) was predicted [Libertini 1988] as well as confirmed and extended in general for all programmed aging hypothesis (Libertini 2008). The prediction of programmed aging hypothesis were confirmed and the opposite prediction of non-programmed aging hypothesis were disproved [Ricklefs 1998].
For programmed aging hypothesis when the conditions favouring aging are absent the prediction is that individuals will not show slow phenoptosis. Note that this prediction is not valid for ages not existing in wild conditions [Libertini 1988; Libertini 2006]. In short, for programmed aging hypotheses, a stable mortality in the adult stage is predicted to be the default condition and “animals with negligible senescence” are not an unexplainable phenomenon but something indispensable for considering programmed aging hypothesis a tenable theory. Well, what are “animals with negligible senescence” for non-programmed aging theories? Their existence can be considered as a strong argument against non-programmed aging theories. Is there any general explanation for them consistent with non-programmed aging theories? Obviously not!
The limits for cell proliferation and cell turnover determined by telomere-telomerase system are a good explanation for aging phenomena at cell and organism level [splendid book of Fossel, 2004]. Telomere-telomerase system is a highly sophisticated system genetically determined and regulated. Programmed aging theories require the existence of specific mechanisms genetically determined and regulated as well as capable of causing an age-related fitness decline: without them the programmed aging hypothesis would be untenable. On the contrary, a non-programmed aging theory does not require such mechanisms and the effects of telomere-telomerase system must be justified with a specific function. A current explanation is that the limit in cell duplication and turnover determined by telomere-telomerase system are a general defense against cancer. Well, in wild populations the increase of mortality rates begins and continues when cancer incidence is irrelevant. For programmed aging theories, this is not a problem because the limits in cell duplication and turnover have another function (to determine aging!), but for non-programmed aging theories, if these limits are not against cancer, how are they explained?
The aging process is very plastic. It can be modulated by genetic as well as environmental factors. Single gene mutations identified in various model organisms can extremely extend the lifespan, by up to 10 fold [Shmookler Reis et al. 2009]. Importantly, it appears that most of these genes are highly conserved between species. Dietary restriction (DR) is a non-genetic intervention, which by limiting defined factors (like total calories, proteins, certain amino acids as well as time) in diet (if it does not cause malnutrition), delays the aging process, prevents almost all age-related diseases (metabolic and cardiovascular disease, neurodegeneration and cancer) and robustly extends healthy lifespan in evolutionary far-separated species, from unicellular yeast to rodents, even primates including humans (e.g. Okinawa).
The current consensus on the evolutionary origin of aging argues against a genetic program. It says that there is no evolutionary selection for limiting the lifespan of animals, as animals in the wild do not live long enough to die by aging. But hold on! The consensus about the reason why DR extends lifespan is that organisms from yeast to mammals evolved a genetic program to cope with periods of starvation that can postpone aging. But this contradicts the major argument against programmed aging: “That aging does not occur in wild”. If there is no evolutionary selection to program aging, which is argued not to occur in the wild, why should there be an evolutionary selection to retard aging, which again is argued not to occur in the wild.
There are actually at least two explanation for the phenomenon of DR which are not exclusively, but rather than complementary. Under conditions/times where there are less nutrients or calories, the animal activates its protection system (hormesis, because it is stress) and retards development, reproduction and growth (reproductive-cell-cycle theory). However, DR reverses rapidly age-related changes [Mair et al. 2003; Dhahbi et al. 2004]. Therefore, DR leads to some kind of reprogramming.
Who says that development ever stops? Individuals display different changes during development as people also age in quite a bit a different manner although more variable, but in essence very uniformly. However, nobody negates that development underlies a program. In aging organisms, aging is actually caused by the continuous action of the developmental growth program. Gene expression changes during aging represent either extension or reversal of developmental program (cessation of growth). Thus, the changes we observe in the adulthood of aging organisms are like the changes in early development tightly regulated, i.e. programmed [Somel et al. 2010].
The action of genes or their changes which are necessary and beneficial early in life become detrimental later in life [Figure: Antagonistic pleiotropy]. A concept called antagonistic pleiotropy, which almost logical solves the “unsolved problem of biology” for the old-paradigm (non-adaptive aging theories). Age-related changes in gene, protein and microRNA expression originate from early development [Somel et al. 2010]. DR might simple retard this developmental growth program. Drugs which counteract or even reverse this progression by targeting the master regulators will restore youthfulness. A couple of drugs which mimic some effects of DR were already shown to extend lifespan (e.g. rapamycin, metformin and spermidine).
Real examples of antagonist pleiotropic acting genes exist to some extent. Although p53 is not a clear-cut example of an antagonist pleiotropic gene, but several components participating in TOR signalling are. In mice, loss of p53 does not increase lifespan, rather than shortens it. In contrast, mildly hyperactive p53 increases lifespan. p53 suppresses senescence and converts senescence into quiescence. Actually, p53 activity declines during aging and is reduced in senescent cells. Thus, p53 could be classified as an anti-aging gene. Early in life the TOR pathway drives developmental program, which persists later in life as a program of aging and age-related diseases. TOR pathway is activated by growth factors (e.g. IGF-1), insulin and other hormones and nutrients. It inhibits autophagy, stimulates ribosome biogenesis, protein synthesis (including aggregate-prone proteins), cell growth and secretion of inflammatory and mitogenic factors. When cell cycle is blocked, TOR drives senescence instead of growth [Blagosklonny, 2010].
In C. elegans it was shown that protein aggregates are inherent to aging and associated to growth. In insulin/IGF-1 signaling longevity mutants certain aggregation-prone proteins were down-regulated and their solubility is also promoted (Jones, 2010). Functional annotation of these aggregate-prone proteins revealed that many of them are known to function early in life, where they play an important role in embryonic development, growth, translation, and protein homeostasis. Furthermore, functional similarities among the aggregate-prone proteins, particular proteins related to proteostasis regulation, show that the process of aggregation is not random [David et al. 2010].
It is general accepted that there is no evolutionary pressure for stopping these growth and developmental processes, because (as it is often argued) after the reproductive peak the animal has usually already transferred its genomic information recombined to the next generation and animals in the wild are usually killed, for example by predators, disease or accident. Importantly, it is also an evolutionary advantage not to stop the developmental program and even be causal for decline in repair and maintenance function, because an animal then does not exerts a negative effect on the survival of its progeny by using necessary resources. Older animals are more experienced and if not reduced in their fitness due to aging, would efficiently impair the fitness of the next generations. Therefore, an elimination of the ancestors would facilitate evolution via promoting the survival and fitness of new and more variances.
Aging is not the result of a general error of all types of cells. If such an error would exist, no animal would escape aging. But such animals, animals with negligible senescence, exist. An example is the non-sexual reproducing sea anemones.
Aging is also not just the accumulation of damage. Also sexual-reproducing life forms have developed efficient repair mechanism which work fantastic until the animal has normally reproduced. Further, damaged biomolecules must be repaired or exchanged otherwise each subsequently generation will be born older and older. Experiments trying to prevent damage or to enhance repair function where shown to be ineffective in extending lifespan (e.g. overexpression of anti-oxidants or DNA repair systems components). It rather appears that animals do have the capacity to repair, but some kind of force prevents the activation of such systems in the adulthood.
Aging can therefore be considered as the consequence of the developmental program. Evolutionary causes determine the developmental program, which includes - for man vertebrates - an age-related fitness decline. This developmental program regulates that in the life history of an animal certain gene activities are changing. For instance, some genes have low or high activity early in development, which reverse at a defined time frame [Figure: Antagonistic pleiotropy]. The continued action of other genes after a certain time point are detrimental because their action is not more needed. For example, it is possible that after the reproductive peak, when morphogenesis is mostly complete, genes which regulate growth and differentiation are not more needed in the same high level as during development. This leads subsequently to the appearance of aging. When the body reaches its optimal size, the mitogenic stimuli cause cells to become senescent. Tissues become more and more differentiated and the stem cell capacity to maintain tissue integrity will be lost.
Aging is not just due to antagonist pleiotropic changes. Although the antagonist pleiotropy explains elegantly many real life observations, it has major problems. It does not explain why there are non-aging species (apparently they do not have antagonist pleiotropy) and the occurrence of highly regulated changes after the reproductive peak, such as menopause.
Non-adaptive aging theories have problems to explain the presence of a developmental regulated program “menopause” (cessation of reproduction) in the post-reproductive phase. Any individual, of whatever age, who is caring for dependent offspring, is acting in a way that promotes the survival of her/his own genes and is probably considered a part of the breeding population [Williams, 1957]. The human menopause cannot just somehow be explained by the grandmother effect, as previously attempted [Kirkwood and Melov 2011]. It is much easier to suggest that humans like lab rats, once a time ago, had females that died just about the time they exhausted their reproductive activity. The reason human females evolved such a long lifespan after menopause was so that their sons could evolve a long lifespan and repopulate the world like Ghengis Kahn. Almost every Asian man is related to Ghengis Kahn (8% of the men in Asia are direct descendants of Ghengis Kahn) [http://www.abc.net.au/science/articles/2003/08/08/917468.htm]. This assumes that the aging mechanism given to offspring is a hybrid of the aging in the female and the male parent.
It need to be stressed that the normalized deviation in ages of death is of the same order of magnitude as that of ages of menarche and menopause. All of them are developmental programmed mechanisms .
Development and aging are not separate, but more like two phases (pre-adulthood & adulthood) of the same timing mechanism. The two phases response differently to environmental influences. In C. elegans for instance, animals in the pre-adulthood encountering food shortage become Dauers (which are ageless, they do not start aging), while animals in the adulthood upon food restriction slow down aging (commonly called CR/DR). However, this means that aging only starts after development is completed and the timing mechanism controlling the progression of development and that of aging might be quite different.
The increase in mortality rate (often defined as aging) stops at very old-ages [Figure: Age-specific mortality over the life history of an aging animal. The age-specific mortality is high for very young (A), but drastically decreases and becomes very low in young adulthood, at their reproductive peak (B, default level). After this, a program progressively increases the age-specific mortality (C), but at very high ages it ceases this action (D). (Comfort, 1956: 16)]. This deceleration of mortality rate was observed in multiple species such as genetically heterogeneous medflies [Carey et al. 1992] genetically inbred Drosophila strain [Curtsinger et al. 1992; Fukui et al. 1993], in genetically heterogeneous (but not genetically inbred) nematodes [Brooks et al. 1994], wasps, yeast and automobiles [Vaupel et al. 1998] and even in human populations [Kannisto et al., 1994; http://www.jstor.org/pss/2137662] Manton et al. 1994].
In humans mortality rate increased after the age of 10 every year to a maximum at 72. After which the rate of change in the mortality rate began to drop and continued to do so through at least age 95. The mortality rate actually decreases sharply in very old humans and appears to follow a special logistic form of the Gompertz curve which takes this mortality deceleration into account. If aging is defined as being an increased probability of dying with the passage of time, then these data compel us to conclude that human aging begins about 10 years of age and ends about 110 years of age with the inflection point of the change being 72 years.
The death of soybean plants occurs soon after maturation of seeds, which can be simply prevented by depodding [Leopold et al. 1959] or deseeding [Lindoo and Nooden 1977]. Pods induce a senescence by producing a death signal killing all leaves. Therefore, semelparous species are actively destroyed once reproduction is completed.
Several species of bamboo have fixed lifespans determined by the time of inflorescence [Weismann 1977].
Senescence and death of a higher organism can be cancelled by means of inactivation of a few genes in its genome. Plants having mutations in soc1 and full genes switched from sexual to vegetative reproduction, do not form seeds, and do not die due to seed-induced senescence. Lifespan increases for 80-90 days to practical infinity [Melzer et al. 2008].
Similar to this plants or C. elegans arrest in dauer, there are very rare cases of developmental arrest in humans, where an individual’s always stay as infants.
It is remarkable that after a seemingly miraculous feat of morphogenesis an organisms should be unable to perform the much simpler task of merely maintaining what is already formed [George Williams, 1957]. How can this be? Group selection is an important evolutionary force.
Alleles can become selected because of the benefits they might render to the group, not to the individual [Fabrizio et al. 2004; Rose, 1991]. The assumption that group selection requires separation of two groups of the same species [Kirkwood and Melov 2011] is wrong. The groups involved in group selection are non-interbreeding groups of animals in the same deme or ecosystem. Thus, the group selection pressure is occurring everywhere all the time, aging rabbits defeat non-aging squirrels at the local level.
Imagine the scenario of two groups of rabbits separated by un-crossable mountains on an island. One group aged, the other did not. Both groups were visited by foxes that killed the non-aging rabbits at will since they were all very similar as there was no turnover from aging. The other group turned over faster due to aging and had more variability in their gene pool, because non-aging rabbits generally all survived the same series of selection events which homogenized their gene pool. Younger rabbits have not all been homogenised by the same series of selection events. Therefore, there was a wide range of faster and slower rabbits among the individuals in the aging group on the other side of the island. The foxes killed a few of the slow ones and thus reduced the slow genes, while the faster gene rabbits continued to reproduce and age. Consequently, a genetic drift wiped out the slow rabbits before the foxes could wipe out all the rabbits. Thus, the fast aging rabbits survived while all the non-aging generally slow rabbits were killed by foxes [Bowles 1998]. This concept although very logical and reasonable was too weak a force of selection. In order to improve the selective force of aging (obviously we and rabbits are not non-aging) we could not allow the non-aging rabbits to breed with the aging rabbits and destroy the advantage of aging. Or maybe we can!
Group selection does not occur between interbreeding species but between different groups of non-interbreeding species in the same ecosystem. So, instead of the non-aging rabbits getting wiped out due to their lower phenotypic diversity vs. aging rabbits, aging rabbits were in competition with non-aging squirrels, non-aging skunks, non-aging raccoons, etc. All with lower phenotypic diversity when it came to a fox attack. Subsequently, the only surviving animal on the whole island visited by foxes, was aging rabbits who maintained a higher phenotypic diversity of individuals. This is the unseen subtle force that selects for aging everywhere all the time. Therefore, in a local ecosystem ants compete with elephants and plants and everything else and it is the world-wide universal pressure that selects for aging (and sex), all the time everywhere.
Things that are universal among most species like aging and sex types and male and female sex display mate choice are all selected for at the local level due to competition to resist extinction from predation. For instance, males of all species share many of the same characteristics. They are either load, colorful, seek danger, become big before females mate with them or grow large appendages that females find attractive and if no predators are around to cull them they fight each other [Williams, 1957]. The one thing all these things have in common are they show a male’s fitness in the face of predator encounters, as bright colours and load sounds attract predators. Any survivors have the right genes, large body size and large appendages and feathers and horns attract females because they show the male’s age (they take a while to grow like human beards). The older the male the more predator encounters he has survived. Thus, both aging and sex are defences to novel predation.
Examining the animals that live way longer than their body sizes should suggest based on that line of body-size/lifespan that show how the larger an animal the longer it maximal lives. Like a mouse lives 2 years, a dog 15 years, a horse 40 years, an elephant 70 years, it is a normal straight upward sloping line. However, there are big exceptions, like bats, which have the size of mice, live 30 years. Humans about the size of a large dog can live 120 years, little lobster can live 220 years, little turtles can live 150 years, some birds like parrots can live 90 years and arctic clams can live 250 years, deep dwelling rock fish can live 150 years. What do they all have in common? They all have a great defense to predators, full body armour, extreme intelligence, flight, and isolation [Figure: Tricks for escaping the force of evolution to develop fast aging system].
We are part of an ecosystem and the reason for a strong selection pressure of evolving and maintaining aging is also due to the interactions of our species with all the other species within this system! If we would not age and die we are not freeing up resources to other species which are themselves provide providing resources or benefits to our progenies and relatives. For some specific biological niches this is not a problem, therefore they evolved immortality. It is these interactions between all the organisms with each other which determines whether a defined species has to age at all and at which pace. It is a ubiquitous constant force. As the aging systems evolved very early in life-time being, these systems are just adjusted to account for the current time of being requirement in order to keep homeostasis in a local ecosystem. Longevity in one species can appear and disappear very dynamically (which is not just on the genetic level, the adjustments are often just of epigenetic nature; it is quicker). Also these genes are so tightly connected to other traits (because they are so ancient) that they can be kept also by other selective forces acting on these traits and indirectly maintaining aging.
This ubiquitous mechanism of group selection becomes obvious and compelling. The reason why grass ages and dies is the same reason the ant and giraffe and bird and bacteria ages and die. All evolving groups competing to occupy the same biomass at the local level. This concept is very simple and yet was not envisioned. It also selects for sex types, male and females, although it is less clear how it works in plants, but in animals it is all the same: Males are expendable go out and attract predators. Whoever survives comes back to repopulate the species and have a harem of females. If predators selection is not intense enough then females select louder brighter bigger males (older), hence the survivor males or males fight to get the right to breed (stimulating fighting off a predator).
Aging systems are still maintained even under protected environment (like capacity or the conditions under which humans are living), in which the local ecosystem is different to the natural one. Aging systems are like a babysitter. When prey species get separated from their predators for long periods of time they would lose their aging systems and evolve longer lifespans as their lives are not cut by the predator and they can work out all the harmful genes, but aging systems make this process take a lot longer. In this sense aging systems are “predator’s babysitters.” If a prey species quickly lost all their aging systems they would go extinct when the predator returns.
Why would they go extinct? It is because they would lose their phenotypic diversity. Non-aging prey species would reproduce to the maximum then stop until one of them dies and they can reproduce to fill the vacancy. The longer the non-aging animals life the longer the same series of selection events they all survive, eventually just one individual survived them all and did all the repopulating thus narrowing the gene pool to clones and if one clone can be killed by the predator they all can. In contrast, an aging group has diversity due to the fact that there has been much less narrowing selection by time to one phenotype.
That is why species in a protected environment do not loss their aging systems. The force is not just restricted to the protection for future predator visits, but applies even more general to everything which is capable of increasing external mortality (viruses, catastrophes... changes in environments in general). In this sense maintaining a high intrinsic mortality provides the huge advantage to make an aging species more adaptive to changes in their habitats.
Thus, aging and sex are duo to the competition of different species for the some energy resources and dynamically shaped by their interplay with their respective predators/environments and resource availability, which of course is to a major extend overlapping. Altruistic behavior occurs also on the ecosystem level, where individuals of one species sacrifice themselves via aging and death to benefit other species in their local deme and consequently support the survival of their own genes present in their progeny and relatives. If a genetically-driven behavior patterns like aging somehow enhances a particular gene’s/allele’s survivability above the level of individuals who do not share it then the gene will very probably become more common in the species, therefore aging genes evolved. It basically means that life history events occurring after the peak of reproduction are under high selective forces executed by the local ecosystem (interspecies competition and altruism), hence aging is selected for, evolved and composed of a highly sophisticated program.
Interspecies altruism is probably due to accident, aberration and/or mistaken identity, at least initially, which results in a case of overzealous co-operation that looks like altruism. The point to note is that if the behavior is genetically governed and it gives a survivability advantage to the practicing organisms, then it will be tend to become more abundant. Such happenstances may lie at the root of symbiotic relationships.
Co-evolution must be understood. Our bodies are highly integrated ecosystems. Even ingested organic materials such as plants can alter our gene expression via miRNAs [http://www.scientificamerican.com/article.cfm?id=vitamins-minerals-and-microrna].
To sum up: Group selection occurs only at the local level between species that do not interbreed. What is the driving force of this selection? Evolving predation. The local ecosystem is full of predators and full of prey. If the predators are evolving quickly, they can eat up all the prey and cause their extinction. However, if the prey are evolving rapidly they can avoid all the predators and cause them to become extinct. Thus, evolvability is important. If a species cannot evolve as quickly as its predator or prey species it will go extinct.
Therefore, each species needs a certain amount of genetic and phenotypic diversity in order to be able to quickly respond (evolve a new defence or new offense) to evolving predators and evolving prey. For this reason, the local ecosystem selects for both sex and aging (sex mixes up 50/50 and shuffles them, which is a lot). Clonally reproducing all females lizards (which make a lot of sense at the individual selection level and actually do exist in a few places) are killed off by faster evolving predators to local extinction, while a lizard species with sex would be able to survive in the same locale. The same with aging. Aging prevents too much reproduction by one individual which reduces the diversity of the gene pool.
So how does aging and sex spread? Almost all non-aging and asexual local groups become extinct when in competition with local aging and sexual groups. Local surviving aging and sexual species migrate to other areas over time where their non-aging and asexual relatives have become extinct.
Thus group selection for sex and aging is a strong force and is occurring everywhere all the time between all local groups. From time to time a local group might revert back to non-sexual reproducing by accident (like the female lizards), but they soon will go extinct.
Only when a species has developed a better defense to predation than increased diversity, it can evolve a longer lifespan than allowed by the body size lifespan continuum. Like birds/bats-flight, clams/lobster/turtles-full body armor, humans/chimps-extreme intelligence, rockfish/deep dwelling fish/arctic clams/desert plants/mountain trees-isolation.
Asexual reproduction and slow aging results often in genetic monotony and disease vulnerability, which is a major disadvantage to them in a changing environment.
The evolutionary pressure to select for sex and aging is a small force but is it ubiquitous and over time wins. That is why long-lived and asexual species are found in the desert. There is very little competition, no need for genetic or phenotypic diversity. Thus, asexual species survive as well as non-aging. Isolation and hyper-specialization is the key here that allows non-aging and non-sexual species to evolve and survive. It also explains why there are many more species at the equator vs. very few species further north or south. Equatorial living takes off the mortality factor of freezing, thus it is all predation.
‘Nothing in nature exists in isolation.’
Disposable-Soma-Theory tries to explain the aging process on the basic of evolution. Basically, it assumes that organisms only have a limited amount of magical energy (is it ATP or what?) that has to be divided between reproductive activities and maintenance of the organisms body (soma).
The concept claims that there is a close connection between lifespan and reproduction. However, numerous longevity mutants, and even DR regimens can easily uncouple longevity from reproduction [Grandison et al. 2009]. Even normal mice can be breed to have higher fertility and increased lifespan [Rostock Meeting 2011, unpublished]. Therefore, longevity and reproduction are not really trait-offs.
Actually, repair mechanism requires less energy than the daily use of energy for functioning of the organism. Post-menopausal woman have more energy and have their reproductive capability elapsed. Animals that live on average longer are reproductively better-off. Females do not generally live longer than males despite that males use less energy for reproduction.
Even the great Darwin suggested that the adverse effect of limited lifespan or aging must have some unknown benefits. Also, it has been proven that reproduction is a natural rejuvenation process. The germline is not per se immortal or ageless, but rather undergoes like the soma age-related changes and utilizes a rejuvenation process to reset the lifespan of the offspring.
Finally, assuming that aging is not regulated, but rather determined by “trait-offs”. Let’s assume that for only one moment that the disposable soma theory is right. In honeybees while workers are very short-lived, queens are extraordinary long-lived (> 20-times). Now, it becomes clear that Disposable-Soma-Fairy Tale is just a big lie, because the long-lived queen is reproducing like crazy, making all the offspring of the colony!
The disposable soma theory was maybe at 1979 appropriate as at this time when conserved families of aging genes were yet unknown and even the science of DR was an esoteric biological backwater. Moreover, the theoretical fashion of the era supported individual selection; there was not yet a science of the era supported multilevel selection, computational literature of viscous populations or even the high-throughput data from the genomics of aging. The disposable soma theory was the right theory for 1979 [Kirkwood and Holliday 1979]. But knowing what we know now, it is obvious there is an imperative to take seriously the idea that aging is a purposeful genetic program that has been conserved by a billion years of natural selection.
The mythical figure of “disposable soma theory” is untenable. It is very important to substitute wrong ideas with hypothesis that are consistent with known data and not with untenable new theories. A sound theory explaining the age-related increasing mortality (alias decreasing fitness), imprecisely called with the term “aging”, must be in accordance with empirical data., e.g.:
The interpretation of aging as the effect of continuation of development might be interpreted as a reformulation of the popular and widely accepted antagonistic pleiotropy hypothesis. However, this theory is a kind of non-programmed aging theory and does not explain and is in contrast with above given evidence and with other phenomena. Continuation of development means in this respect that changes we observe in adulthood of aging organisms are not random or just responses to damage, but rather than under genetic control and tightly regulated. In many species, e.g. Rockfish, the “continuation of development” is the unlimited persistence of the youthful condition.
If one really want to understand the evolutionary “why” and the physiological “how” of aging, one should leave the wrong convictions of the old paradigm and became a heretical (as few of us are). It is a difficult way but this is the future for brilliant and ambitious scientists [Libertini, 2009]. For those which are not ambitious, they can follow the old paradigm and do not contradict its dogma.
We need the viewpoint (fresh-eyes), creativity and ideas of new scientists. They are young and inexperienced, but this is an essential strong advantage when it is necessary to pass from an old paradigm (aging as non-adaptive phenomenon) to a new concept (aging as adaptive phenomenon). It is a sort of “duel to the death” [Figure: Duel of Death. Which site are you choosing?]. It was observed that for the acceptance of a new paradigm it is necessary a new generation [Kuhn and Hacking 2012].
In physics there are many examples of such paradigm shifts (from Kopernikus, Galileo, and relativity theory to quantum mechanics). It is very funny that Kirkwood refers to Galileo and at the same time represents such an old dogma [Kirkwood and Melov 2011]. Actually, Terra (earth) is not just orbiting around sol (sun), the truth is that in relative terms sol is also orbiting around terra and the whole solar system revolves around the center of our galaxy which itself is in motion and so forth. Thus, keeping aging to be non-adaptive and referring to a numerous increasing number of exceptions “which prove the rule” is just as to continuing thinking that everything in our universe can be explained by classic physics and matter has no waveform character.
Bowles JT. 1998. The evolution of aging: a new approach to an old problem of biology. Medical hypotheses 51(3): 179-221.
Brooks A, Lithgow GJ, Johnson TE. 1994. Mortality rates in a genetically heterogeneous population of Caenorhabditis elegans. Science 263(5147): 668-671.
Carey JR, Liedo P, Orozco D, Vaupel JW. 1992. Slowing of mortality rates at older ages in large medfly cohorts. Science 258(5081): 457-461. Curtsinger JW, Fukui HH, Townsend DR, Vaupel JW. 1992. Demography of genotypes: failure of the limited life-span paradigm in Drosophila melanogaster. Science 258(5081): 461-463.
David DC, Ollikainen N, Trinidad JC, Cary MP, Burlingame AL, Kenyon C. 2010. Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS biology 8(8): e1000450.
Dhahbi JM, Kim HJ, Mote PL, Beaver RJ, Spindler SR. 2004. Temporal linkage between the phenotypic and genomic responses to caloric restriction. Proceedings of the National Academy of Sciences of the United States of America 101(15): 5524-5529.
Fukui HH, Xiu L, Curtsinger JW. 1993. Slowing of age-specific mortality rates in Drosophila melanogaster. Exp Gerontol 28(6): 585-599.
Grandison RC, Piper MD, Partridge L. 2009. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462(7276): 1061-1064.
Kirkwood TB, Austad SN. 2000. Why do we age? Nature 408(6809): 233-238.
Kirkwood TB, Holliday R. 1979. The evolution of ageing and longevity. Proc R Soc Lond B Biol Sci 205(1161): 531-546.
Kirkwood TB, Melov S. 2011. On the Programmed/Non-Programmed Nature of Ageing within the Life History. Current biology : CB 21(18): R701-707. Kuhn TS, Hacking I. 2012. The structure of scientific revolutions. The University of Chicago Press, Chicago ; London.
Leopold AC, Niedergang-Kamien E, Janick J. 1959. Experimental Modification of Plant Senescence. Plant physiology 34(5): 570-573.
Libertini G. 1988. An adaptive theory of increasing mortality with increasing chronological age in populations in the wild. Journal of theoretical biology 132(2): 145-162.
Libertini G. 2006. Evolutionary explanations of the "actuarial senescence in the wild" and of the "state of senility". TheScientificWorldJournal 6: 1086-1108.
Libertini G. 2008. Empirical evidence for various evolutionary hypotheses on species demonstrating increasing mortality with increasing chronological age in the wild. TheScientificWorldJournal 8: 182-193.
Lindoo SJ, Nooden LD. 1977. Studies on the behavior of the senescence signal in anoka soybeans. Plant physiology 59(6): 1136-1140.
Mair W, Goymer P, Pletcher SD, Partridge L. 2003. Demography of dietary restriction and death in Drosophila. Science 301(5640): 1731-1733.
Manton KG, Stallard E, Woodbury MA, Dowd JE. 1994. Time-varying covariates in models of human mortality and aging: multidimensional generalizations of the Gompertz. Journal of gerontology 49(4): B169-190.
Martins AC. 2011. Change and aging senescence as an adaptation. PloS one 6(9): e24328.
Melzer S, Lens F, Gennen J, Vanneste S, Rohde A, Beeckman T. 2008. Flowering-time genes modulate meristem determinacy and growth form in Arabidopsis thaliana. Nature genetics 40(12): 1489-1492.
Oakwood M, Bradley AJ, Cockburn A. 2001. Semelparity in a large marsupial. Proceedings Biological sciences / The Royal Society 268(1465): 407-411.
Ricklefs RE. 1998. Evolutionary theories of aging: confirmation of a fundamental prediction, with implications for the genetic basis and evolution of life span. The American naturalist 152(1): 24-44.
Ruckenstuhl C, Carmona-Gutierrez D, Madeo F. 2010. The sweet taste of death: glucose triggers apoptosis during yeast chronological aging. Aging 2(10): 643-649.
Severin FF, Hyman AA. 2002. Pheromone induces programmed cell death in S. cerevisiae. Current biology : CB 12(7): R233-235.
Shmookler Reis RJ, Bharill P, Tazearslan C, Ayyadevara S. 2009. Extreme-longevity mutations orchestrate silencing of multiple signaling pathways. Biochimica et biophysica acta 1790(10): 1075-1083.
Somel M, Guo S, Fu N, Yan Z, Hu HY, Xu Y, Yuan Y, Ning Z, Hu Y, Menzel C et al. 2010. MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome research 20(9): 1207-1218.
Travis JM. 2004. The evolution of programmed death in a spatially structured population. The journals of gerontology Series A, Biological sciences and medical sciences 59(4): 301-305.
Vaupel JW, Carey JR, Christensen K, Johnson TE, Yashin AI, Holm NV, Iachine IA, Kannisto V, Khazaeli AA, Liedo P et al. 1998. Biodemographic trajectories of longevity. Science 280(5365): 855-860.
Weismann A. 1977. Essays upon heredity and kindred biological problems. Dabor Science Publications, Oceanside, N.Y.
Somel M, Guo S, Fu N, Yan Z, Hu HY, Xu Y, Yuan Y, Ning Z, Hu Y, Menzel C, Hu H, Lachmann M, Zeng R, Chen W, Khaitovich P (2010) MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome research 20: 1207-18.
Skulachev VP (1999) Mitochondrial physiology and pathology; concepts of programmed death of organelles, cells and organisms. Molecular aspects of medicine 20: 139-84.
Skulachev VP. Aging and the programmed death phenomena. In Topics in Current Genetics. Model systems in ageing. T. Nystrom and H.D. Osiewacz, Eds. (Springer‐Verlag, Berlin‐Heidelberg). 2003; v. 3, pp. 191‐238.
Bradley AJ, McDonald IR, Lee AK (1980) Stress and mortality in a small marsupial (Antechinus stuartii, Macleay). General and comparative endocrinology 40: 188-200.
Skulachev, V P (1997) Aging is a specific biological function rather than the result of a disorder in complex living systems: biochemical evidence in support of Weismann's hypothesis. Biochemistry (Mosc) 62: 1191-5.
Skulachev, V P (1999) Phenoptosis: programmed death of an organism. Biochemistry (Mosc) 64: 1418-26.
Comfort A. The biology of senescence (Edinburg-London, Churchill Livingstone). 1979.
Finch C. Longevity, Senescence, and the Genome (Chicago-London, University Chicago Press). 1990.
Raff M (1998) Cell suicide for beginners. Nature 396: 119-22.
Lewis K (2000) Programmed death in bacteria. Microbiology and molecular biology reviews : MMBR 64: 503-14.
Dan I, Watanabe NM, Kusumi A (2001) The Ste20 group kinases as regulators of MAP kinase cascades. Trends in cell biology 11: 220-30.
Goldsmith TC (2004) Aging as an evolved characteristic - Weismann's theory reconsidered. Medical hypotheses 62: 304-8.
Loison A, Festa-Bianchet M, Gaillard JM, Jorgenson JT, and Jullien JM. Age-specific survival in five populations of ungulates: Evidence of senescence. Ecology. 1999; 80: 2539-2554.
Bradley AJ, McDonald IR, and Lee AK. Stress and mortality in a small marsupial (Antechinus stuartii, Macleay). Gen Comp Endocrinol. 1980; 40: 188-200.
Fabrizio P, Battistella L, Vardavas R, Gattazzo C, Liou LL, Diaspro A, Dossen JW, Gralla EB, Longo VD (2004) Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae. The Journal of cell biology 166: 1055-67.
Rose MR. 1991. Evolutionary Biology of Aging (New York: Oxford University Press).