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Revamping the Evolutionary Theories of Aging

evolution of aging mutation accumulation antagonistic pleiotropy disposable soma lifespan extrinsic mortality

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#1 Engadin

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Posted 08 September 2019 - 09:00 PM





S O U R C E :    ScienceDirect







•Extrinsic mortality is one of the most important drivers in the evolution of aging.
•Classical predictions expect higher extrinsic mortality to shorten evolved lifespan.
•The bulk of published data conform to the classical evolutionary theories of aging.
•Increased extrinsic mortality can sometimes select for longer evolved lifespans.
•Immortal animals that experience extrinsic mortality challenge classical theories.
•The aging response to extrinsic mortality involves multiple interacting factors.
Radical lifespan disparities exist in the animal kingdom. While the ocean quahog can survive for half a millennium, the mayfly survives for less than 48 hours. The evolutionary theories of aging seek to explain why such stark longevity differences exist and why a deleterious process like aging evolved. The classical mutation accumulation, antagonistic pleiotropy, and disposable soma theories predict that increased extrinsic mortality should select for the evolution of shorter lifespans and vice versa. Most experimental and comparative field studies conform to this prediction. Indeed, animals with extreme longevity (e.g., Greenland shark, bowhead whale, giant tortoise, vestimentiferan tubeworms) typically experience minimal predation. However, data from guppies, nematodes, and computational models show that increased extrinsic mortality can sometimes lead to longer evolved lifespans. The existence of theoretically immortal animals that experience extrinsic mortality – like planarian flatworms, panther worms, and hydra – further challenges classical assumptions. Octopuses pose another puzzle by exhibiting short lifespans and an uncanny intelligence, the latter of which is often associated with longevity and reduced extrinsic mortality. The evolutionary response to extrinsic mortality is likely dependent on multiple interacting factors in the organism, population, and ecology, including food availability, population density, reproductive cost, age-mortality interactions, and the mortality source.



1. Introduction


One of the major, unsolved mysteries in biology is the evolution of aging. It remains to be elucidated why there is so much variability in lifespan across the animal kingdom and why aging evolved at all. It is non-intuitive to expect that a harmful process like senescence, which decreases fitness and increases mortality, would be favored by natural selection. The concept of the evolution of aging was introduced into the literature in 1930 by Ronald Fisher (Fisher, 1930). Thanks to Fisher and innovative thinkers like Peter Medawar (Medawar, 1952), George Williams (Williams, 1957), William Hamilton (Hamilton, 1966), Thomas Kirkwood (Kirkwood, 1977), and others, cogent evolutionary theories exist which help explain why aging evolved as well as many of the observed disparities in longevity between different species. According to these classical theories, extrinsic mortality (e.g., predation, disease, starvation, accidents) is a primary evolutionary driver of how quickly or slowly an organism will age. Since most animals in the wild will not survive to old age due to harsh living conditions, there is little to no evolutionary pressure to promote genetic changes that slow aging and increase lifespan. This is certainly true for wild mice, where their major cause of mortality is cold temperature (Berry and Bronson, 1992) and more than 90% of mice will die in their first year of life (Kirkwood, 2005). For these reasons, there should typically be strong evolutionary pressure to encourage genes that promote early survival and more rapid reproduction.


Given high mortality rates in the wild, it is thought that the force of evolutionary selection for self-maintenance will decline with age for most animals (Fig. 1A). This declining selection gradient with age underlies Medawar’s “mutation accumulation” theory (Medawar, 1952), which argues that deleterious, late-acting mutations can accumulate passively without resistance (Fig. 1B). Building off of Medawar’s work, the later-developed “antagonistic pleiotropy” theory proposed by Williams (Williams, 1957) posits that the rarity of senescence in the wild results in a more active selection for genes that benefit early life but impair late life (Fig. 1C). These theories were formalized mathematically and further developed by Hamilton (Hamilton, 1966). The more mechanical, energy-focused “disposable soma” theory by Kirkwood (Kirkwood, 1977) emphasizes that, because resources are limited, most organisms will fare best if they invest their finite energy into mechanisms that boost fecundity instead of non-reproductive mechanisms (i.e., the soma) that combat aging (Fig. 1D). Both the antagonistic pleiotropy and disposable soma theories expect a trade-off between aging and fecundity (Flatt and Partridge, 2018). All three theories predict that an increase in extrinsic mortality should select for the evolution of shorter lifespans and vice-versa.



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Fig. 1. Classical theories for the evolution of aging. A) Illustration of Medawar’s “selection shadow” showing that deleterious mutations are subject to a decreasing selective pressure after sexual maturation. B) The mutation accumulation theory emphasizes the lack of selection against mutations that exert deleterious effects later in life. C) The antagonistic pleiotropy theory argues for the selection of mutations that improve reproduction at the cost of repair, resulting in a direct antagonism. D) The disposable soma theory focuses on mechanistic trade-offs between repair and reproduction through a shared resource pool.



The bulk of published observations conform to these predictions (Kirkwood and Austad, 2000) and new data continues to emerge that further bolsters these classical evolutionary theories of aging. For example, deep-sea animals live in a stable environment, experience minimal predation, and tend to live significantly longer compared to their shallow-water counterparts. A recent paper reported that large, deep-sea vestimentiferan tubeworms enjoy extreme longevities, regularly obtaining lifespans of 100-200 years and exhibiting a maximal lifespan of over 300 years (Durkin et al., 2017). As an explicit example of the role of predation in the evolution of aging, exposure to the predatory mosquito Toxorhynchites rutilus during the juvenile stage has been shown to shorten the lifespan of adults in Aedes aegypti mosquitoes. Increased predation also decreased development time and hastened recruitment to the adult stage (Bellamy and Alto, 2018). Further highlighting a trade-off between reproduction and aging, reduced longevity is associated with a high mating rate in wild antler flies (Bonduriansky and Brassil, 2005).


Although significantly rarer, important studies have defied classical predictions by showing that increased extrinsic mortality can select for the evolution of longer lifespans. Two seminal studies performed in guppies (Reznick et al., 2004) and nematodes (Chen and Maklakov, 2012) showed that, in response to an increase in extrinsic mortality, a longer lifespan could be selected for. Using an agent-based, stochastic computational model, we previously demonstrated that whether increased predation selects for the evolution of longer or shorter lifespans can depend heavily on parameters like the cost of mating and energy availability (Shokhirev and Johnson, 2014). The existence of theoretically ageless animals, like planarian flatworms (Sahu et al., 2017), panther worms (Srivastava et al., 2014), hydra (Martinez, 1998), and immortal jellyfish (Schmich et al., 2007) that appear not to undergo senescence create an additional challenge for the evolution of aging. Since these theoretically immortal animals do experience extrinsic mortality, why would they develop such powerful anti-aging mechanisms?


Comparing lifespans between evolutionarily similar animals within the same ecological order reveals how much more we have to learn regarding the evolution of aging. Different species within the order Octopoda, for example, exhibit significantly disparate lifespans. A great illustration of this is the deep-sea octopus Graneledone boreopacifica, which has been documented to have a brooding period of 53 months (Robison et al., 2014), making it the longest living known octopus by even the most conservative projection of this animal’s full lifespan. Unlike many coastal or shallow water octopuses that reside in protective dens, this species was consistently documented to be brooding out in the open – a strong indication that predators are not a major concern at such oceanic depths (Godfrey-Smith, 2016). The brooding period documented is itself significant, as many shallow water octopuses have a lifespan of approximately one year (Anderson et al., 2002). However, significant variability in lifespan exists between different deep-sea octopus species and between different shallow-water octopus species. This suggests, as expected, that other variables are contributing to these longevity differences other than predation, which is the quintessential example of extrinsic mortality used in discussions involving the evolution of aging. The uncanny intelligence of octopuses paired with their short lifespan also makes them a unique evolutionary puzzle (Godfrey-Smith, 2016), as intelligence is typically associated with reduced extrinsic mortality and longer lifespans (Kirkwood, 2005).


This review summarizes the extant literature both supporting and challenging the three classical evolutionary theories of aging. The role of extrinsic mortality is especially emphasized, as this has been consistently shown to be the predominant variable impacting an organism’s evolved lifespan. Other influential variables, such as food availability, fecundity, age-specificity of mortality, and population density, are also discussed. Lastly, we offer new insights which aim to revamp existing evolutionary theories of aging and empower them to coherently integrate all of the existing data. To keep the review a manageable length, we focus on animals with a clear-cut distinction between parents and offspring.



2. Data Supporting the Classical Evolutionary Theories of Aging


2.1. Field observations and comparative studies


According to the mutation accumulation, antagonistic pleiotropy, and disposable soma theories, we should expect extrinsic mortality and lifespan to be inversely correlated with one another. According to the antagonistic pleiotropy and disposable soma theories, we should also expect to see a trade-off between reproduction and longevity. All three of these theories are compatible with one another and are not mutually exclusive. As such, they can be collectively referred to as classical theories when describing data that supports or contradicts them.


A large array of field data from many different animal species conforms to these classical predictions. Influential work by Steven Austad has shown that an insular opossum population with a four-to five-thousand-year history of insulation showed greater survivorship, reduced litter sizes, slower acceleration of age-specific mortality, and slower aging of tail tendon fibers compared to mainland opossums (Austad, 1993). Unlike the insular environment, opossums in the mainland were subject to greater predation and therefore greater extrinsic mortality (Austad, 1993). In another island study, lifespan in the extinct, insular bovid Myotragus balearicus was ascertained by studying dental durability in fossil samples. Estimated longevity was twice as long as what was predicted given their body mass (Jordana et al., 2012). A separate study investigating fossils of these endemic island goats found that, after settling in an island environment, this animal’s brain and sense organs evolved to shrink in size. The reduced brain size and the shrunken sense organs were presumed to be an adaptive strategy to maximize energy use given the lack of predation and the limited availability of trophic resources (Kohler and Moya-Sola, 2004). Bovid longevity increases with sociality for both sexes and this increase is attributed to sociality being a key ungulate strategy to mitigate predation. In only males, bovid longevity was also shown to decrease with male-biased sexual size-dimorphism, an evolutionary trait thought to confer a competitive advantage in contests over mates (Bro-Jorgensen, 2012). These bovid studies conform to classical predications by showing a trade-off between reproduction and longevity and by supporting a causal, inverse link between extrinsic mortality and aging.


Flying animals inhabit a less densely populated ecosystem that is presumed to have less predation and disease compared to the terrestrial environment. Their unique ability to fly also allows them to quickly traverse large swaths of land, thereby granting them access to a much larger food supply. This would be expected to mitigate the risk of starvation as well as allow them to quickly escape hazardous environments. A comparative analysis of longevity among 64 different bat species showed that, on average, a bat’s maximum recorded lifespan is 3.5 times longer than that of a land-dwelling placental mammal of similar size (Wilkinson and South, 2002). Many bats, despite their small size, have been documented to live for over 30 years in the wild (Wilkinson and South, 2002). The Brandt’s bat can live to at least 41 years (Podlutsky et al., 2005), which is especially noteworthy given that they have a small body mass and that, generally, body size is positively correlated with lifespan (Austad and Fischer, 1991). Among different species of bats, longevity is best predicted by body mass and hibernation. For both hibernators and non-hibernators, longer lifespans are correlated with cave use (Wilkinson and Adams, 2019).


Analogously to bats, birds live about three times longer than an average non-flying mammal of similar size. Despite a rapid metabolic rate and an elevated body temperature, they also show an uncanny resistance to age-related degeneration (Austad, 2011) and an ability to maintain a robust healthspan until the near end of life (Ricklefs, 2010a). It has been suggested that, because of the high aerobic demands of flying, a selection for high aerobic capacity may account for the longer lifespans of birds and bats (Lane, 2011). Notable long-lived examples of birds are the northern fulmar and the Manx shearwater, both of which have a longevity record of 51 years (Austad, 2011). A separate analysis of 271 species of birds found a strongly positive relationship between adult survival rate (i.e., low extrinsic mortality) and relative longevity. Relative longevity was also related to the timing of first reproduction and these two parameters were covaried (Moller, 2006). Across 124 taxonomic families of terrestrial vertebrates, the rate of aging decreases with increasing body mass, age at maturity, gestation period, and possession of flight. Actuarial senescence, or the rate of increase in adult mortality with age, was positively related to extrinsic mortality rate and negatively related to age at maturity and gestation period (Ricklefs, 2010b). Within volant species, lifespan depends on whether the species is active in the day, night, dusk, or dawn and the longest lived birds and mammals tend to be diurnal or nocturnal (Healy et al., 2014). Since fliers active at dusk or dawn would theoretically be predated on by both diurnal and nocturnal predators, this lifespan difference has been thought to stem from disparate rates of predation (Healy et al., 2014).


Among non-fliers, adaptations that would be expected to reduce extrinsic mortality are strongly correlated with boosted longevity. Shattuck and Williams analyzed published data on 776 species and discovered that, assuming common body sizes, arboreal mammals are longer lived than terrestrial animals. This trend was independent of phylogeny and further subclade analyses showed that this trend held true for almost every mammalian subgroup (Shattuck and Williams, 2010). The two exceptions were primates (and their close relatives) and marsupials, both of which experienced a persistent and long evolutionary history in trees prior to transitioning to terrestriality (Shattuck and Williams, 2010). The additional protection from hazards and predators in an arboreal environment further supports the theory that less extrinsic mortality allows for the evolution of longer lifespans. The ability to dig, another trait that could reduce extrinsic mortality levels, is also associated with longer lifespans among terrestrial animals (Healy et al., 2014). In addition, shells and large brains are linked with elongated life and thought to minimize extrinsic mortality sources like predation (Kirkwood, 2005). Theoretically, large brains would be expected to also reduce starvation risk by enabling tool use as well as the ability to obtain and consume more diverse types of food. A detailed analysis is warranted to determine if, akin to traits like flight and arboreality, tool use is positively correlated with longer lifespans.


As a nice illustration of how adaptations that reduce extrinsic mortality are correlated with longer lifespans, the four longest-lived rodents are the eastern grey squirrel, the American beaver, the North American porcupine, and the naked mole-rat (Gorbunova et al., 2008). Squirrels are well known for their ability to deftly evade predators and beavers are the largest rodents in the world that build complex lodges and burrows. Porcupines are massive in size and have the benefit of being covered in sharp, protective quills. They are also adept climbers that spend a portion of their time in trees. Naked mole rats are subterranean, eusocial rodents that live underground in an isolated, dark tunnel environment. All four of these rodents have traits which should increase their odds of surviving to old age (Gorbunova et al., 2008). The naked mole rat, in particular, is a powerful example of an animal that has an incredibly long lifespan for its body size. It also has a remarkable healthspan characterized by negligible senescence, uncanny cancer-resistance, high fecundity until death, and no age-related increase in mortality. Consistent with these traits, genome sequencing of the naked mole rat (Heterocephalus glaber) has shown that these animals have unique adaptations in genes involved in cancer resistance, DNA repair, DNA replication, and telomerase function (Kim et al., 2011). While oncogenesis is rare in naked mole rats, it is important to note that they are not completely immune to it. Different forms of cancers have been documented in zoo-housed animals (Delaney et al., 2016Taylor et al., 2017).


Several studies have explored the link between extrinsic mortality and aging in aquatic animals. In natural populations of sockeye salmon, the fish that showed the slowest progression of senescence were those where brown bears selectively killed fish showing advanced senescence (Carlson et al., 2007). In the live-bearing fish Brachyrhaphis rhabdophora, animals in predator environments were found to experience higher overall mortality and proportionally higher adult mortality rates compared to fish from predator-free environments. Within the predator-free environments, the most important life-history stages for population growth occurred late in life. This contrasted with predator environments, where the most important life-history stages for population growth were found early in life (Johnson and Zuniga-Vega, 2009). As would be expected, annual fish of the genus Nothobranchius from a dry region were more susceptible to habitat cessation and had shorter lifespans compared to fish from a humid region. Fish from the dry region also accumulated lipofuscin – a pigment that tends to accumulate in organs with age – faster under natural conditions, suggesting that physiological deterioration is more rapid in these animals (Tozzini et al., 2013). Daphnia from temporary ponds exhibit higher juvenile growth, higher early fitness, shorter lifespans, and more rapid senescence compared to daphnia from permanent lakes (Dudycha and Tessier, 1999). A follow-up study found that asexual daphnia clones enjoyed longer lifespans and appeared to age more slowly compared to sexual clones of daphnia, further highlighting a trade-off between aging and fecundity (Dudycha and Hassel, 2013). The African turquoise killifish (Nothobranchius furzeri), which is an emerging animal model for aging research in vertebrates, can enter into a state of damage-resistant diapause in response to external stressors like drought. While in this state, killifish exhibit an exceptional resistance to stress and damage (Hu and Brunet, 2018). This diapause response likely evolved to help survives long droughts, which frequently occur in the habitats of these animals. Interestingly, these fish struggle to survive in a harsh environment and also have one of the shortest – if not the shortest – lifespan among vertebrates (Hu and Brunet, 2018). This association between high extrinsic mortality (i.e., drought) and fast aging lends further credence to traditional predictions.


Clade-focused data from reptiles and amphibians also support classical evolutionary theory. An assessment of 1193 species of non-chemically protected (not venomous or poisonous) and chemically protected (venomous or poisonous) newts, frogs, toads, salamanders, snakes, and fishes revealed that species with chemical protection more frequently exhibited longer lifespans than species without chemical protection (Blanco and Sherman, 2005). This study (Blanco and Sherman, 2005) as well as a later study showed that larger body sizes were positively correlated with lifespan in both amphibians and snakes. In the latter work, maximum lifespan was positively correlated with chemical protection in amphibians but not in snakes. This is potentially due to chemical protection being primarily offensive in snakes and defensive in amphibians (Hossie et al., 2013). Larger body size and chemical protection would both be expected to result in a reduction in predation. Further supporting classical expectations, western terrestrial garter snakes from a low-predation meadow environment evolved longer lifespans than those from a high-predation lakeshore environment (Robert and Bronikowski, 2010). Compared to the short-lived snakes, the long-lived snakes were smaller in size, repaired DNA damage more efficiently, harbored more efficient mitochondria, and had more robust cellular antioxidant defenses. Short-lived snakes from the high-predator lakeshore environment grew faster, matured earlier, and had larger litter sizes compared to long-lived snakes from the low-predator meadow environment (Robert and Bronikowski, 2010).


In humans, mortality data from historical cohorts and subsistence populations from England/Wales and Sweden reveals that slower actuarial aging is associated with reduced extrinsic mortality in longitudinal samples (Gurven and Fenelon, 2009). Using longitudinal demographic records in Utah, it was shown that human reproductive rates have declined over time. As these rates have declined, female lifespan has increased. In contrast, male lifespan has remained largely stable. Since only women pay a major cost to reproduction, it has been theorized that the additional longevity of women in this cohort is a result of reduced reproductive costs (Bolund et al., 2016). A more recent study by Helle did not find strong evidence for a trade-off between post-reproductive mortality and lifetime reproductive effort in a large dataset of 6,594 women from pre-industrial, northern Sweden (Helle, 2018). Separate work analyzing fertility and longevity in 6,359 women born in the Netherlands between 1850 and 1910 did not find evidence for an initial linear trade-off between these variables (Kaptijn et al., 2015). Prior to any of these mentioned studies, a literature review collated the existing data and assessed whether or not there was a cost for reproduction in human beings. The author concluded that, under natural fertility conditions, longevity and fertility are not inversely correlated. However, some evidence suggests that mortality slightly increases when women have more than five children in modern populations (Le Bourg, 2007). Given the complexity of human culture and its introduction of many confounding variables, it is important to emphasize how challenging it is to assess the relationship between lifespan and mortality in human beings.



2.2. Laboratory studies


Most laboratory studies investigating the evolution of aging have done so in fruit flies. Much like the comparative and field studies discussed above, the bulk of the data indicates that extrinsic mortality and intrinsic mortality (i.e., rate of aging) are negatively correlated and that there is a trade-off between reproduction and longevity.


Work by Stearns et al from 1998 found that artificially increasing extrinsic mortality rates in Drosophila melanogaster led to the evolution of shorter lifespans and higher intrinsic mortality rates. 90% or 20% of flies in a cage were killed and replaced each week for the high adult mortality and low adult mortality conditions, respectively (Stearns et al., 1998). Flies subjected to high adult mortality developed faster, hatched at a smaller size, and laid more eggs early in life (Stearns et al., 1998). A subsequent paper by Stearns et al confirmed that higher intrinsic mortality rates and shorter lifespans evolve in response to higher extrinsic mortality. An elevated mortality rate also decreased the age and size at eclosion and shifted peak fecundity to earlier in life. Both larval density and food quality were tweaked during this experiment (Stearns et al., 2000). For both of these studies, population densities were maintained at a constant level by replacing deceased flies under both low- and high-mortality conditions (Stearns et al., 1998Stearns et al., 2000). Separate work by Gasser et al showed that high adult mortality impacted ovariole number, growth rate, and life-body size but did not affect desiccation resistance, starvation resistance, activity, metabolic rate, viability, or body composition (relative fat content). More specifically, there were more functional ovarioles, life-body size was smaller, and growth rate was higher in flies subjected to higher extrinsic mortality (Gasser et al., 2000).


While only a handful of studies have explicitly studied the role of extrinsic mortality in the evolution of aging using flies in the laboratory, several projects have investigated the trade-off between fecundity and aging. Work by Michael Rose has shown that culturing fly populations at later ages (i.e., only allowing surviving older females to reproduce) increases female longevity, enhances late fecundity, and depresses early fecundity (Rose, 1984). Partridge et al bred Drosophila from either old or young adults to generate flies that were longer-lived and shorter-lived, respectively, and showed that flies bred from older adults evolved an increase in survival and a decline in early life fertility. No increase in late-life fertility was observed and no correlated responses to selection were observed in larval competitive ability, adult size, or development time (Partridge et al., 1999). Rose and Charlesworth reported that a selection for late fecundity extended female longevity, increased the duration of female reproduction, decreased mean egg-laying rate, and decreased early fecundity (Rose and Charlesworth, 1981). This trade-off between aging and fecundity in flies bred for longevity is further corroborated by data presented by Luckinbill et al (Luckinbill et al., 1984). In a separate study presented by Luckinbill and Clare, the selection of late-life reproductive success required a high larval density. No obvious effect on the evolution of aging was observed when larval density was held low (Luckinbill and Clare, 1985). A more recent paper published in 2015 further confirmed a trade-off between reproduction and aging in D. melanogaster by demonstrating that females with a genetic propensity to mate more often live shorter lives (Travers et al., 2015). Important work by Sgrò and Partridge has shown that the sterilization of female flies either by the ovoD mutation or by x-ray irradiation reduces age-related mortality (Sgro and Partridge, 1999). While this list is by no means comprehensive, it serves to show that a trade-off between aging and fecundity is well documented in fruit flies.


In experiments with the freshwater snail Physa acuta, snails were reared in the absence or presence of chemical cues from predatory crayfish and mated either early in life or late in life. Both predation risk and age reduced overall reproductive success and this reproductive decline was three times faster under predation risk conditions compared to the no-predator condition. While this initially appears to challenge predictions made by classical theories, this decline in reproductive success was due to a negative effect on post-hatching survival (Auld and Houser, 2015). Therefore, less overall reproduction appeared to occur due to reduced survival rates and a shorter period of time being available for reproduction. This work highlights the imperative role predation plays in the evolution of aging as it shows that, independent of actual extrinsic mortality, the mere threat of predation is sufficient to affect survival and reproduction. A 2016 study from the same research group compared snails that were either allotted or excluded the offer to mate with an unrelated partner. Mated snails experienced a significant reduction in survival probability, a finding the authors interpreted as a result of shifting resource allocation (Auld et al., 2016). Mate availability was separately shown to reduce final size and juvenile growth rate (Auld and Relyea, 2008). Overall, these experiments bolster classical theories by highlighting mechanistic trade-offs between growth, aging, and fecundity.


Weaver ants are eusocial insects where major, large workers perform risky tasks outside the nest while minor, small workers reside in a highly protected arboreal nest. To assess whether or not intrinsic aging differed between small and large workers, Chapuisat and Keller established experimental colonies of Oecophylla smaragdina weaver ants that were collected from Townsville, Queensland, Australia (Chapuisat and Keller, 2002). They discovered that the minor workers from the arboreal, nested environment lived significantly longer than the major workers that performed work outside of the nest (Chapuisat and Keller, 2002). In the larger insect Melanoplus sanguinipes, grasshoppers from different populations that occur along an altitudinal gradient in the Sierra Nevada in California were reared in two different thermal culture conditions. Mortality rates increased with age at each temperature and, for each condition, grasshoppers originating from low-elevation populations enjoyed longer lifespans and lower mortality rates than their counterparts from higher elevations. Elevated sites would theoretically be marked by more severe and sudden winter conditions, which could be a source of extrinsic mortality that would explain the observed differences in survival (Tatar et al., 1997).


In the nematode Strongyloides ratti, there are distinct free-living and parasitic adults. Rat intestine-dwelling parasitic adults have a maximum reported lifespan of 403 days while soil-dwelling parasitic adults have a maximum reported lifespan of five days. This 80-fold difference in lifespan is presumed to be due to different rates of extrinsic mortality in the intestine and soil (Gardner et al., 2006). In Caenorhabditis elegans nematodes, the partial loss of function of the insulin receptor-like protein DAF-2 extends lifespan but results in a heavy fitness cost. DAF-2 mutant worms go extinct more rapidly and show a significant reduction in early fertility (Jenkins et al., 2004). In this same nematode species, a mutation in the age-1 gene that extends lifespan in C. elegans did not have any fitness cost under standard laboratory conditions. When subjected to starvation cycles that could mimic field conditions, however, a fitness cost was revealed in this long-lived mutant (Walker et al., 2000). This is similar to a study done in Drosophila, where mutation of the Indy gene generates long-lived flies and decreases the slope of the mortality curve, thereby appearing to slow the rate of aging. Under the condition of a decreased-calorie diet, long-lived mutants displayed reduced fecundity. Under standard feed conditions, no reduction in age-specific fecundity was observed (Marden et al., 2003). Data from these latter two studies indicate that standard laboratory conditions may hide significant trade-offs between aging and fitness. If a trade-off is not observed under standard laboratory conditions, various stressors should be tested to determine if there is indeed a fitness cost associated with an extended lifespan.



3. Data Challenging the Classical Evolutionary Theories of Aging


3.1. Field observations and comparative studies


A significant paper defying standard predictions comes from the Austad laboratory. In this paper, Nussey et al presented evidence of senescence in the wild in 175 different animal species from 340 studies. The evidence of senescence in natural populations of mammals, birds, other vertebrates, and insects (Nussey et al., 2013) suggest that aging may not be exempt from natural selection as much as has been historically assumed. Some field data also do not suggest an inverse relationship between extrinsic mortality and lifespan. Despite its assumed ability to decrease extrinsic mortality, foraging group size was not correlated with maximum longevity in a sample of 421 North American birds. Body mass did, however, increase with longevity in non-passerine birds (Beauchamp, 2010). Although group size would be expected to reduce an individual’s risk of predation, a separate analysis of 253 mammalian species found group size to be a poor predictor of maximum longevity across all mammals as well as within rodents and primates. A weak, yet significant group-size effect in the negative direction was found for artiodactyl longevity (Kamilar et al., 2010).


With regards to reproduction, no evidence for a trade-off between self-maintenance and reproduction was observed in the long-lived seabird Sterna hirundo, even in old age (Apanius and Nisbet, 2006). Broadly speaking, queens in eusocial colonies with their high longevity and high fecundity defy the traditional prediction of a trade-off between aging and reproduction (Flatt and Partridge, 2018). Similarly defiant of classical expectations, breeders live significantly longer than helpers in social African mole-rats (Dammann et al., 2011). Naked mole rats maintain high reproductive potential throughout old age and, in the Blanding’s turtle and the painted turtle, older females lay more eggs and have more consistent annual reproduction than younger adults (Finch, 2009). Impressive work by Jones et al highlights the diversity of animal life histories by contrasting age patterns of mortality and reproduction for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants, and a green alga (Jones et al., 2014). The authors show that virtually every combination of mortality and fertility patterns is possible, including bowed, humped, decreasing, constant, and increasing trajectories for both short-lived and long-lived species (Jones et al., 2014). These data make it clear that fecundity and aging can relate to each other in many different ways. Future research should aim to understand what circumstances give rise to the mélange of life history trajectories that exist in nature.



3.2. Laboratory studies


Seminal work directly challenging classical predictions comes from data on guppies from David Reznick and his collaborators. Guppies (Poecilia reticulata) in streams were found to have significantly higher predation rates than guppies by waterfalls, where predators are often excluded. Predators increase the guppy mortality rate of all age and size classes and, within the low-predation waterfall site, the odds of surviving for six months is 20-30 times higher than in the high-predation stream site (Reznick et al., 2001aReznick et al., 1996). High predation localities tended to have higher levels of food availability compared to the low predation localities. Concomitant with this reduction of food availability, guppies from low predation localities had smaller asymptotic body sizes and lower growth rates (Reznick, 1982Reznick et al., 2001b). In their impactful 2004 Nature paper, Reznick et al reared guppies from high predation and low predation localities in the laboratory. As would be expected from classical predictions, high predation guppies reproduced more frequently, produced more offspring in each litter, and matured at a significantly earlier age (Reznick et al., 2004). In addition to having an earlier maturation age, they also ceased reproduction at a later age and sustained a higher rate of offspring production throughout their life. Unexpectedly, guppies from high predation localities enjoyed a lower rate of aging and longer total lifespans. Using a fast start escape response assay to asses neuromuscular performance, it was found that high-predation guppies were significantly faster than low-predation guppies while young but were statistically similar while old. As such, a more rapid age-related deterioration of physiological performance was observed in high-predation guppies. All fish, regardless of predation risk, showed a decrease in neuromuscular performance with age, making this a good marker of guppy senescence (Reznick et al., 2004). In a follow-up study in guppies from low-predation environments, density manipulation experiments were performed to see if guppies were sensitive to density regulation. Decreased population density resulted in decreased juvenile mortality rates, increased juvenile growth, and an increased reproductive investment by adult females. Increased population density led to increased adult mortality, decreased fat storage by adult females, and reduced offspring size (Reznick et al., 2012).


Another pioneering study defying classical expectations was performed by Chen and Maklakov in the nematode Caenorhabditis remanei (Chen and Maklakov, 2012). Although they found that random mortality selected for the evolution of shorter lifespans, they discovered that heat-induced mortality selected for the evolution of longer lifespans. This condition-specific mortality source slows, immobilizes, or kills worms and only the healthiest survivors were therefore transferred to the next generation. Irrespective of the mortality source used (condition-specific vs. random), increased mortality rates resulted in the evolution of females with increased fecundity. Under the conditions tested, the condition-specific lifespan extension was not initially associated with a reproductive trade-off. Nematodes are naturally exposed to higher temperatures and, since increased temperature is associated with increased immunity and thought to increase the proportion of vigorous individuals in the population, the authors theorized that the heat condition uniquely selected for robust, fit individuals (Chen and Maklakov, 2012). While female fecundity was increased in response to increased extrinsic mortality, follow-up work from the Maklakov laboratory discovered that condition-specific mortality resulted in reduced early life and net reproduction in males (Chen et al., 2016). Regardless of the extrinsic mortality source used (random or condition-dependent), the TOR inhibitor rapamycin was able to additively extend lifespan. This would suggest that the evolution of longer lifespans in heat-stressed nematodes occurs, at least partially, via a route independent of the nutrient sensing TOR pathway.


For comparison, a new source of condition-specific mortality was applied in these worms that selected for faster-moving male individuals. Immobilized females were utilized as a pheromone source and only the first 20% of males that arrived at the pheromone spot were maintained in the population and allowed to reproduce. Using this conditional mortality regime, a new population evolved where male chemotaxis was more rapid compared to males evolved under random mortality. Unlike random mortality, where longevity decreased, male longevity evolved to increase in the condition-specific population. Compared to the random mortality condition, male mating proficiency was increased under the condition-specific mortality condition (Chen and Maklakov, 2014). Interestingly, C. remanei females are both the shorter-lived sex and the sex with higher learning ability. Young females more rapidly learn a novel association between bacterial food and the odor butanone. Female offspring production and learning ability decline rapidly with age while these traits are maintained at high levels until mid-age for males (Zwoinska et al., 2013). Haphazard extrinsic mortality erodes the sex-based aging difference in these nematodes, where males typically live longer than females (Chen and Maklakov, 2014). These data suggest complex trade-offs between aging, reproduction, movement, and learning ability in C. remanei. More broadly, these data indicate that gender roles play an important role in the evolution of aging.


These significant studies in guppies and nematodes make it clear that, contrary to classical predictions, an increase in extrinsic mortality can select for the evolution of longer lifespans (Chen and Maklakov, 20122014Reznick et al., 2004). While these data corroborate the imperative role extrinsic mortality plays in guiding the evolution of aging, they also make it clear that condition-specific mortality can have distinct effects compared to random mortality. Condition-specific mortality can select for individuals that have more robust internal repair mechanisms, thereby resulting in the evolution of longer life. Moreover, under a regime of a more haphazard mortality (i.e., predation), there are specific conditions that can allow for the evolution of longer lifespans despite an increase in a mortality source. Data from guppies suggest that factors like food availability and population density interact closely with parameters like predation, aging, and fecundity. More specifically, higher rates of predation can decrease the population size, thereby increasing the total number of resources available to each individual.


In our previous stochastic modeling study (Shokhirev and Johnson, 2014), we used a simulated annealing approach to predict what factors might allow for the evolution of longer or shorter lifespans in response to increased predation. When mating costs were relatively low and food was relatively scarce, we found that shorter lifespans evolved in response to increased predation. Conversely, longer lifespans were able to evolve in response to higher extrinsic mortality if energy was available in excess and if the cost of mating was relatively high. We also found that an elevated rate of predation decreased the total population size, increased the shared resource pool, and redistributed energy reserves for mature individuals (Shokhirev and Johnson, 2014). Data from guppies appears to match the predictions of our computational model. High predation guppy localities had an enlarged food supply compared to low predation localities (Reznick, 1982Reznick et al., 2001b). Likewise, both population density was a critical parameter that had to be tinkered with to successfully select for the evolution of longer lifespan in laboratory fruit flies (Luckinbill and Clare, 1985). Population density was also shown to be a potent regulator of mortality, growth, reproduction, size, and fat storage in guppies (Reznick et al., 2012). With regards to the relative cost of mating, guppies are promiscuous fish in which females receive no material benefits and males provide no resources (Evans and Magurran, 2000). In particular, mating increases a female’s vulnerability to both predation and parasites as well as leads to a reduction in foraging efficiency (Evans and Magurran, 2000). As predicted by our stochastic model (Shokhirev and Johnson, 2014), a good argument could be made that there is a relatively high cost of mating in these fish.


There are several laboratory studies that challenge the classical assumption of a trade-off between aging and fecundity. In Cardiocondyla obscurior ants, for example, queens from single- and two-queen colonies enjoyed both higher fecundity and boosted longevity compared to queens living in associations of eight queens under similar levels of extrinsic mortality (Schrempf et al., 2011). A positive relationship between longevity and reproductive success also exists in reared wild-caught queens from the bumblebee Bombus terrestris audax (Lopez-Vaamonde et al., 2009). Combined chemostat cultures containing rotifers from ephemeral and permanent hydroperiods enjoy a 56% increase in asexual fecundity and a 23% decrease in the rate of aging (Smith and Snell, 2014). In daphnia reared from lakes either with or without the predator anadromous alewife, daphnia from predator-containing lakes generated significantly more offspring throughout their lifetime. However, no differences in survival or in age-related declines in fertility were observed (Walsh et al., 2014). In two different mosquito species, transgenically increasing Akt signaling not only extended lifespan but also increased yolk protein production (Arik et al., 2015). Although egg production was not significantly impacted, the increase in yolk protein suggests that this aging intervention may offer a mild reproductive benefit in addition to boosting longevity. As an additional indicator that reproduction is not always at odds with aging, neither laser ablation of the entire gonad nor complete sterilization of the already long-lived, fertility-impaired daf-2 mutant results in life extension in C. elegans (Flatt, 2011). Wit et al did not identify a trade-off between early fecundity and lifespan in their longevity selection lines and instead found that females had analogous or higher fecundity throughout life compared to controls. Long-lived flies were also more starvation-resistant (Wit et al., 2013). Similarly, flies with recombinant genotypes have been documented to exhibit an elevation in both longevity and early fecundity (Khazaeli and Curtsinger, 2013). It is important to note that, for any of these studies, a currently unknown trade-off involving reproduction may exist under certain conditions



3.3. Octopus longevity


Octopuses pose an interesting challenge for the evolution of aging (Godfrey-Smith, 2016) by both bolstering and defying traditional expectations. A comparison of maximum lifespans between different octopus species (Table 1) conforms to the standard predictions of the mutation accumulation, antagonistic pleiotropy, and disposable soma theories. Maximum longevity varies wildly among different species (Table 1) and can fluctuate anywhere from ˜7 months to 11+ years (Doubleday et al., 2008Doubleday et al., 2011Forsythe and Hanlon, 1988Herwig et al., 2012High, 1976Leporati and Hart, 2015Leporati et al., 2015Leporati et al., 2008Ramos et al., 2014Regueira et al., 2015Robison et al., 2014Wood et al., 1998). Most of the species with documented lifespans have maximal longevities hovering around 1.5 years (Table 1). Of those studied, the longest-lived species are either deep-sea dwellers like G. boreopacifica (Robison et al., 2014) and Bathypolypus arcticus (Wood et al., 1998) or are atypically large in size like the giant pacific octopus Enteroctopus dofleini (High, 1976). As we have already discussed, both deep-sea dwelling and increased size are associated with reduced extrinsic mortality. Relevantly, the longest brooding period documented for any animal – terrestrial or aquatic – was in the deep-sea octopus G. boreopacifica. Via repeated remote-operated vehicle visits, a single female was documented to brood for 53 continuous months. The previous octopus brooding record was 14 months and was laboratory-documented in the deep-sea octopod B. arcticus (Wood et al., 1998). The estimated lifespan for B. arcticus is approximately three years (O’Dor and Macalaster, 1983), which is ˜2.5X greater than the recorded brooding stage. Applying this same scaling to G. boreopacifica, these longer brooders would be expected to live for ˜11 years, making them the longest-lived known octopods. Other octopus species brood for about a quarter of their lifespan (Robison et al., 2014), which would mean that G. boreopacifica could theoretically live for over 17 years. Interestingly, the brooding mother was never documented to eat during any of the remote-operated vehicle visits and ignored pieces of crab that were offered to her (Robison et al., 2014). It has been previously theorized that the life-extending effects of caloric restriction (Balasubramanian et al., 2017) evolved as an adaptation to better cope with periods of famine (Kirkwood and Shanley, 2005). In addition to reduced predation, this suggests that food availability and food consumption may contribute to this animal’s unique life history.











F O R    T H E   R E S T   O F   T H E   S T U D Y ,   P L E A S E   V I S I T   T H E   S O U R C E .






Edited by Engadin, 08 September 2019 - 09:04 PM.

Also tagged with one or more of these keywords: evolution of aging, mutation accumulation, antagonistic pleiotropy, disposable soma, lifespan, extrinsic mortality

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