Lecture 17: Aging: Physiological and evolutionary explanations (Learning Objectives and Questions)

Explain the physiological explanations for aging.

* Physical direct causes... ex. Physiological changes occur with aging in all organ systems. The cardiac output decreases, blood pressure increases and arteriosclerosis develops. The lungs show impaired gas exchange, a decrease in vital capacity and slower expiratory flow rates. Aging: The Biology of Senescence Entropy always wins. Each multicellular organism, using energy from the sun, is able to develop and maintain its identity for only so long. Then deterioration prevails over synthesis, and the organism ages. Aging can be defined as the time-related deterioration of the physiological functions necessary for survival and fertility. The characteristics of aging—as distinguished from diseases of aging (such as cancer and heart disease)—affect all the individuals of a species. Many evolutionary biologists (Medawar 1952; Kirkwood 1977) would deny that aging is part of the genetic repertoire of an animal. Rather, they would consider aging to be the default state occurring after the animal has fulfilled the requirements of natural selection. After its offspring are born and raised, the animal can die. Indeed, in many organisms, from moths to salmon, this is exactly what happens. As soon as the eggs are fertilized and laid, the adults die. However, recent studies have indicated that there are genetic components to senescence, and that the genetically determined life span characteristic of a species can be modulated by altering genes or diet. Go to: Maximum Life Span and Life Expectancy The maximum life span is a characteristic of the species. It is the maximum number of years a member of that species has been known to survive. The maximum human life span is estimated to be 121 years (Arking 1998). The life spans of tortoises and lake trout are both unknown, but are estimated to be more than 150 years. The maximum life span of a domestic dog is about 20 years, and that of a laboratory mouse is 4.5 years. If a Drosophila fruit fly survives to eclose (in the wild, over 90% die as larvae), it has a maximum life span of 3 months. However, a person cannot expect to live 121 years, and most mice in the wild do not live to celebrate their first birthday. The life expectancy, the amount of time a member of a species can expect to live, is not characteristic of species, but of populations. It is usually defined as the age at which half the population still survives. A baby born in England in the 1780s could expect to live to be 35 years old. In Massachusetts during that same time, the life expectancy was 28 years. This was the normal range of human life expectancy for most of the human race in most times. Even today, the life expectancy in some areas of the world (Cambodia, Togo, Afghanistan, and several other countries) is less than 40 years. In the United States, a child born in 1986 can expect to live 71 years if male and 78 years if female.* Given that in most times and places, humans did not live much past 40 years, our awareness of human aging is relatively new. A 65-year-old person was rare in colonial America, but is a common sight today. Some survival curves for female Homo sapiens in the United States are plotted in Figure 18.35. In 1900, 50% of American women were dead by age 58. In 1980, 50% of American women were dead by age 81. Thus, the phenomena of senescence and the diseases of aging are much more common today than they were a century ago. In 1900, people did not have the "luxury" of dying from heart attacks or cancers. These diseases generally occur in people over the age of 50 years. Rather, people died (as they are still dying in many parts of the world) from infectious diseases and parasites (Arking 1998). Similarly, until recently, relatively few people exhibited the more general human sensecent phenotype: graying hair, sagging and wrinkling skin, joint stiffness, osteoporosis (loss of bone calcium), loss of muscle fibers and muscular strength, memory loss, eyesight deterioration, and the slowing of sexual responsiveness. As Shakespeare noted in As You Like It, those who did survive to senescence left the world "sans teeth, sans eyes, sans taste, sans everything." Causes of Aging The general senescent phenotype is characteristic of each species. But what causes it? This question can be asked at many levels. We will be looking primarily at the cellular level of organization. Even here, there is evidence for many different theories, and there is not yet a consensus on what causes aging. Oxidative damage One major theory sees our metabolism as the cause of our aging. According to this theory, aging is a by-product of normal metabolism; no mutations are required. About 2-3% of the oxygen atoms taken up by the mitochondria are reduced insufficiently to reactive oxygen species (ROS). These ROS include the superoxide ion, the hydroxyl radical, and hydrogen peroxide. ROS can oxidize and damage cell membranes, proteins, and nucleic acids. Evidence for this theory includes the observation that Drosophila that overexpress enzymes that destroy ROS (catalase, which degrades peroxide, and superoxide dismutase) live 30-40% longer than do controls (Orr and Sohal 1994; Parkes et al. 1998). Moreover, flies with mutations in the methuselah gene (named after the Biblical fellow said to have lived 969 years) live 35% longer than wild-type flies. The methusaleh mutants have enhanced resistance to paraquat, a poison that works by generating ROS within cells (Lin et al. 1998). These findings not only suggest that aging is under genetic control, but also provide evidence for the role of ROS in the aging process. In C. elegans, too, individuals with mutations that increase the synthesis of ROS-degrading enzymes live much longer than wild-type nematodes (Larsen 1993; Vanfleteren and De Vreese 1996). The evidence for ROS involvement in mammalian aging is not as clear. Mutations in mice that result in the lack of certain ROS-degrading enzymes do not cause premature aging (Ho et al. 1997; Melov et al. 1998). However, there may be more genetic redundancy in mammals than in invertebrates, and other genes may be up-regulated to produce related ROS-degrading enzymes. Migliaccio and colleagues (1999) have observed mutant mice that live one-third longer than their wild-type littermates. These mice lack a particular protein, p66shc. They develop normally, but the lack of p66shc apparently gives them cellular resistance to ROS, and thus higher resistance to oxygen-induced stress on membranes and proteins. The p66shc protein may be a component of a signal transduction pathway that leads to apoptosis upon oxygen stress, and it may be involved in mediating the life spans of mammals. Another type of evidence does suggest that ROS may be important in mammalian aging: aging in mammals can be slowed by caloric restriction (Lee et al. 1999). However, caloric restriction can also have other effects, so it is not certain if it works by preventing ROS synthesis. Also, vitamins E and C are both ROS inhibitors, and vitamin E increases the longevity of flies and nematodes when it is added to their diet (Balin et al. 1993; Kakkar et al. 1996). However, results in mammals are not as easy to interpret, and there is no clear evidence that ROS inhibitors work as well as in invertebrates (Arking 1998). General wear-and-tear and genetic instability "Wear-and-tear" theories of aging are among the oldest hypotheses proposed to account for the general scenescent phenotype (Weismann 1891; Szilard 1959). As one gets older, small traumas to the body build up. Point mutations increase in number, and the efficiencies of the enzymes encoded by our genes decrease. Moreover, if a mutation occured in a part of the protein synthetic apparatus, the cell would make a large percentage of faulty proteins (Orgel 1963). If mutations arose in the DNA-synthesizing enzymes, the rate of mutations would be expected to increase markedly, and Murray and Holliday (1981) have documented such faulty DNA polymerases in senescent cells. Likewise, DNA repair may be important in preventing senescence, and species whose members' cells have more efficient DNA repair enzymes live longer (Figure 18.36; Hart and Setlow 1974). Moreover, genetic defects in DNA repair enzymes can produce premature aging syndromes in humans (Yu et al. 1996; Sun et al. 1998). Mitochondrial genome damage The mutation rate in mitochondria is 10-20 times faster than the nuclear DNA mutation rate (Johnson et al. 1999). It is thought that mutations in mitochondria could (1) lead to defects in energy production, (2) lead to the production of ROS by faulty electron transport, and/or (3) induce apoptosis. Age-dependent declines in mitochondrial function are seen in many animals, including humans (Boffoli et al. 1994). A recent report (Michikawa et al. 1999) shows that there are "hot spots" for age-related mutations in the mitochondrial genome, and that mitochondria with these mutations have a higher replication frequency than wild-type mitochondria. Thus, the mutants are able to outcompete the wild-type mitochondria and eventually dominate the cell and its progeny. Moreover, the mutations may not only allow more ROS to be made, but may make the mitochondrial DNA more susceptible to ROS-mediated damage. Telomere shortening Telomeres are repeated DNA sequences at the ends of chromosomes. They are not replicated by DNA polymerase, and they will shorten at each cell division unless maintained by telomerase. Telomerase adds the telomere onto the chromosome at each cell division. Most mammalian somatic tissues lack telomerase, so it has been proposed (Salk 1982; Harley et al. 1990) that telomere shortening could be a "clock" that eventually prohibits the cells from dividing any more. When human fibroblasts are cultured, they can divide only a certain number of times, and their telomeres shorten. If these cells are made to express telomerase, they can continue dividing (Bodnar et al. 1998; Vaziri and Benchimol 1998). However, there is no correlation between telomere length and the life span of an animal (humans have much shorter telomeres than mice), nor is there a correlation between human telomere length and a person's age (Cristofalo et al. 1998). Telomerase-deficient mice do not show profound aging defects, which we would expect if telomerase were the major factor in determining the rate of aging (Rudolph et al. 1999). It has been suggested that telomere-dependent inhibition of cell division might serve primarily as a defense against cancer rather than as a kind of "aging clock." Genetic aging programs Several genes have been shown to affect aging. In humans, Hutchinson-Gilford progeria syndrome causes children to age rapidly and to die (usually of heart failure) as early as 12 years (Figure 18.37). It is caused by a dominant mutant gene, and its symptoms include thin skin with age spots, resorbed bone mass, hair loss, and arteriosclerosis. A similar syndrome is caused by mutations of the klotho gene in mice (Kuro-o et al. 1997). The functions of the products of these genes are not known, but they are thought to be involved in suppressing the aging phenotypes. These proteins may be extremely important in determining the timing of senescence. In C. elegans, there appear to be at least two genetic pathways that affect aging. The first pathway involves the decision to remain a larva or to continue growth. After hatching, the C. elegans larva proceeds through four instar stages, after which it can become an adult or (if the nematodes are overcrowded or if there is insufficient food) can enter a nonfeeding, metabolically dormant dauer stage. It can remain a dauer larva for up to 6 months, rather than becoming an adult that lives only a few weeks. When it comes out of the dauer stage, it will live as long as if it had never been a dauer larva. In the dauer stage, adult development is suppressed, and extra defenses against ROS are synthesized. If some of the genes involved in this pathway are mutated, adult development is allowed, but the ROS defenses are still made. The resulting adults live twice to four times as long as wild-type adults (Figure 18.38; Friedman and Johnson 1988). The second pathway involves the gonads. Germ cells appear to inhibit longevity, while the somatic cells of the gonads act to prolong the life of the nematode (Hsin and Kenyon 1999). As human life expectancy increases due to our increased ability to prevent and cure disease, we are still left with a general aging syndrome that is characteristic of our species. Unless attention is paid to the general aging syndrome, we risk ending up like Tithonios, the miserable wretch of Greek mythology to whom the gods awarded eternal life, but not eternal youth.

Explain the evolutionary explanations for aging.

Aging is an Evolutionary Paradox Why do we age and die? Aging, or senescence as it is sometimes called, is an inevitable progressive deterioration of physiological function with increasing age, demographically characterized by an age-dependent increase in mortality and decline of fecundity (Rose 1991, Bronikowksi & Flatt 2010, see Figure 1). This poses an evolutionary paradox: natural selection designs organisms for optimal survival and reproductive success (Darwinian fitness), so why does evolution not prevent aging in the first place? For centuries, beginning with Aristotle, scientists and philosophers have struggled to resolve this enigma. The Roman poet and philosopher Lucretius, for example, argued in his De Rerum Natura (On the Nature of Things) that aging and death are beneficial because they make room for the next generation (Bailey 1947), a view that persisted among biologists well into the 20th century. The famous 19th century German biologist, August Weissmann, for instance, suggested - similar to Lucretius - that selection might favor the evolution of a death mechanism that ensures species survival by making space for more youthful, reproductively prolific individuals (Weissmann 1891). But this explanation turns out to be wrong. Since the cost of death to individuals likely exceeds the benefit to the group or species, and because long-lived individuals leave more offspring than short-lived individuals (given equivalent reproductive output), selection would not favor such a death mechanism. A more parsimonious evolutionary explanation for the existence of aging therefore requires an explanation that is based on individual fitness and selection, not on group selection. This was understood in the 1940's and 1950's by three evolutionary biologists, J.B.S. Haldane, Peter B. Medawar and George C. Williams, who realized that aging does not evolve for the "good of the species". Instead, they argued, aging evolves because natural selection becomes inefficient at maintaining function (and fitness) at old age. Their ideas were later mathematically formalized by William D. Hamilton and Brian Charlesworth in the 1960's and 1970's, and today they are empirically well supported. Below we review these major evolutionary insights and the empirical evidence for why we grow old and die. For further in-depth coverage of the evolution of aging we point the reader to Rose (1991), Hughes & Reynolds (2005), Promislow & Bronikowski (2006), Flatt & Schmidt (2009), and references therein. Also see Rauschert (2010) and Shefferson (2010) in Nature Education Knowledge. The Force of Selection Declines with Age As mentioned above, the key conceptual insight that allowed Medawar, Williams, and others, to develop the evolutionary theory of aging is based on the notion that the force of natural selection, a measure of how effectively selection acts on survival rate or fecundity as a function of age, declines with progressive age (see Hamilton 1966, Charlesworth 2000, Rose et al. 2007) (Figure 2). This was first noted, though not formally analyzed, by Fisher in his famous book The Genetical Theory of Natural Selection (1930), and both Haldane (1941) and Medawar (1946, 1952) came to the same conclusion. Haldane (1941) proposed that the declining strength of selection with age might explain the relatively high prevalence of the dominant allele causing Huntington's disease: he speculated that, since Huntington's typically only affects people beyond age 30, such a disease would not have been efficiently eliminated by selection in ancestral, pre-modern populations because most people would already have died well before they could experience this late-onset disease. Thus, the disease would not have been "seen" by, or subject to, selection. Based on Fisher's and Haldane's ideas, Medawar (1946, 1952) worked out the first complete verbal and graphical model of how aging evolves (also see next section). The gist of Medawar's argument is as follows. First, for most organisms, the natural world is dangerous since it abounds with competitors, predators, pathogens, accidents, and other hazards. It follows from this that in natural populations most individuals die or get killed before they can grow old and suffer the symptoms of aging: thus, individuals have a very small overall probability of being alive and reproductive at an advanced age (e.g., Moorad & Promislow 2010). Second, the strength of natural selection declines with increasing age (Figure 2), such that selection ignores the performance of individuals late in life. As a consequence, selection is unable to favor beneficial effects, or to counteract deleterious effects, when these effects are expressed at advanced ages. For example, if a beneficial or deleterious mutation occurs only after reproduction has ceased, then it will not affect fitness (reproductive success) and can therefore not be efficiently selected for or against. However, even if a mutation occurs earlier, say during the reproductive period, its effects may not be visible to selection since, if extrinsic, environmentally imposed mortality is high, individuals that could express the mutation are likely to be dead already. The Mutation Accumulation Hypothesis Following the logic outlined above, Medawar (1946, 1952) reasoned that, if the effects of a deleterious mutation were restricted to late ages, when reproduction has largely stopped and future survival is unlikely, carriers of the negative mutation would have already passed it on to the next generation before the negative late-life effects would become apparent. In such a situation, natural selection would be weak and inefficient at eliminating such a mutation, and over evolutionary time such effectively neutral mutations would accumulate in the population by genetic drift, which in turn would lead to the evolution of aging. This is known as Medawar's mutation accumulation (MA) hypothesis (Figure 3A). The effects of such a mutation accumulation process would only become manifest at the organismal level after the environment changes such that individuals experience less extrinsic mortality (e.g., due to decreased predation) and thus live to an age where they actually express the symptoms of aging. The Antagonistic Pleiotropy Hypothesis In an influential paper published in Evolution, George C. Williams (1957) took Medawar's ideas a step further. If it is true that selection cannot counteract deleterious effects at old age, he argued, then mutations or alleles might exist that have opposite, pleiotropic effects at different ages: genetic variants that on the one hand exhibit beneficial effects on fitness early in life, when selection is strong, but that on the other hand have deleterious effects late in life, when selection is already weak. This idea is known today as the antagonistic pleiotropy (AP) hypothesis for the evolution of aging (see Rose 1991, Flatt & Promislow 2007, Figure 3B). Williams pointed out that, if the beneficial effects of such mutations early in life outweigh their deleterious effects at advanced age, such genetic variants would be favored and enriched in a population, thus leading to the evolution of aging. Thus, under Williams' hypothesis, the evolution of aging can be seen as a maladaptive byproduct of selection for survival and reproduction during youth. A fundamental corollary of Williams' AP hypothesis is that early fitness components such as reproduction should genetically trade-off with late fitness components such as survival at old age, so that, for example, genotypes with high early fecundity should be shorter lived than those with low reproduction (e.g., Williams 1957, Rose 1991, Charlesworth 1994, Hughes & Reynolds 2005). In a somewhat similar vein, Kirkwood's 1977 "disposable soma" (DS) hypothesis predicts that the optimal level of investment into somatic maintenance and repair will evolve to be below that required for indefinite survival. The idea here is that the evolution of a higher investment is unlikely to pay off since the return from such an investment may never be realized due to extrinsic mortality. Moreover, investment into reproduction - or early fitness components in general - might withdraw limited resources that could otherwise be used for somatic maintenance and repair. Such resource allocation trade-offs can thus been seen as a physiological extension of Williams' AP model. Although the relative frequency of MA versus AP is still debated (both may typically go hand in hand - see also Moorad & Promislow 2009), there is robust evidence today for the existence of fitness trade-offs that are consistent with the notion of AP (for a recent discussion of the positive evidence see Flatt & Promislow 2007, and Flatt 2011, but also see Moorad & Promislow 2009). Whether such trade-offs are physiologically caused by competitive energy or resource allocation - as would be expected under the DS hypothesis - remains somewhat controversial, but the trade-offs themselves are well established (see Flatt 2011). Most importantly, the kinds of trade-offs postulated by Williams, have been found at the evolutionary level: for example, fruit flies that were artificially selected for increased late-life reproductive success were found to be long-lived at the expense of reduced early fecundity in several, now classical, experiments in the labs of Michael Rose and Leo Luckinbill (Rose & Charlesworth 1980, Rose 1984, Luckinbill et al. 1984). These elegant experiments represent the first solid empirical tests of the evolutionary theory of aging (Rose 1991). The classical evolutionary theory of aging has therefore two fundamental cornerstones: MA and AP. However, it is worth noting that both models are conceptually very similar: under MA, aging evolves through the accumulation of effectively neutral mutations with deleterious late-life effects, whereas, under AP, aging occurs due to mutations with beneficial early- and deleterious late-life effects. In reality, probably both types of mutations occur in populations, yet their relative frequencies remain unknown. Furthermore, the age distribution of mutational effects may be much more complicated than these two scenarios suggest (e.g., Moorad & Promislow 2008). Different organisms vary dramatically in their lifespan (Figure 4). Obviously, aging negatively affects the duration of life since it increases the risk of death. These intrinsic, maladaptive effects of aging, unchecked by selection, are, however, not the only factors affecting the length of life. Independent of whether aging occurs or not, reproductive lifespan can evolve adaptively in response to selection for increased reproductive success (Stearns 1992). A longer lifespan normally implies increased reproductive success, and factors such as low adult mortality (permitting more reproductive events per lifetime), high juvenile mortality (making it necessary for adults to reproductively compensate for such loss), and high variation in juvenile mortality from one bout of reproduction to the next (increasing uncertainty in reproductive success and requiring reproductive compensation as well) therefore all tend to lengthen reproductive lifespan (Stearns 1992). These lifespan promoting effects of selection are balanced by those that tend to increase adult mortality relative to juvenile mortality. Consequently, if extrinsic, environmentally imposed adult mortality is high, selection becomes weak, thereby allowing the evolution of higher levels of intrinsic mortality (i.e., aging). Moreover, even though selection might favor increased reproductive success, and thus a longer reproductive lifespan, the length of life might be limited by intrinsic trade-offs between reproduction and survival caused by AP. Thus, the evolution of lifespan can be viewed as a balance between selection for increased reproductive success and the factors that increase the intrinsic age-dependent components of mortality (Stearns 1992). These ideas have been empirically tested and corroborated by several researchers. For example, using an elegant experimental evolution design, Stearns et al. (2000) exposed fruit flies to either high or low levels of extrinsic adult mortality (HAM versus LAM) and found that LAM flies evolved significantly lower levels of intrinsic mortality relative to HAM flies: in other words, HAM flies evolved more rapid aging than LAM flies. Given that there is ample genetic variation for lifespan and the rate of aging, and given that aging can readily evolve by MA and/or AP, is aging then likely to be universal among species? Clearly, there is a remarkable amount of variation in lifespan among different species, including some extremely short-lived as well long-lived species (e.g., Finch 1990, Figure 4). A lot of this diversity in lifespan can be quite readily explained by variation in the levels of extrinsic mortality and the evolution of different optimal lengths of reproductive life, including the existence of semelparous organisms that reproduce only once and then die (Stearns 1992). For example, species that are well protected from predators - for example, those that have a shell, can fly, or are poisonous - tend to live longer than related, less well-protected species (e.g., Austad & Fischer 1991, Blanco & Sherman 2005). But are there immortal organisms? Although examples of organisms that age very slowly are well known (e.g., Finch 1990, see Figure 4), it is not yet sufficiently clear whether there exist species that truly do not age at all. Bacteria are a good case in point. For a long time it was thought that bacteria do not age. Indeed, one of Williams' (1957) strongest assertions about the evolution of aging was that only organisms with a separation of germ line and soma should age. In such organisms, the germ line is maintained indefinitely, but the aging soma is "disposable" after fulfilling its reproductive role. Bacteria, by contrast, do not exhibit a clear delineation into germ line and soma, and should therefore be immortal. More important than this lack of a clear germ line/soma distinction, however, is the fact that prokaryotes, protozoans, algae, and symmetrically dividing unicells, do not have clearly delineated age classes (Rose 1991, Partridge & Barton 1993). In symmetrically dividing unicells, for example, individuals should not age because parent and offspring are phenotypically indistinguishable - it is impossible to determine old from young, and age is thus invisible to selection. By the same logic, aging should exist in asymmetrically reproducing organisms where aging parents are phenotypically distinct from offspring. Indeed, an asymmetrically dividing bacterium has recently been found to show senescence (Ackermann et al. 2003). Remarkably, however, even the symmetrically dividing E. coli ages: it shows subcellular mother-offspring asymmetry, delineating age classes upon which selection can act to produce senescence (Stewart et al. 2005). Moreover, Ackermann et al. (2007) modeled the origin of aging in the history of life and found that, even when cells divide symmetrically, unicellulars readily evolve a state of asymmetric, unequal distribution of cellular damage among daughter cells. However, as soon as such an asymmetry evolves, aging evolves. Thus, aging - despite remarkable variation in the duration of life among different species - might be a fundamental and inevitable property of cellular life. Summary We have introduced what evolutionary biologists think about the evolution of aging. Today, it is clear that aging is not a positively selected, programmed death process, and has not evolved for "the good of the species". Instead, aging is a feature of life that exists because selection is weak and ineffective at maintaining survival, reproduction, and somatic repair at old age. Based on the observation that the force of selection declines as a function of age, two main hypotheses have been formulated to explain why organisms grow old and die: the mutation accumulation (MA) and the antagonistic pleiotropy (AP) hypotheses. Under MA, aging evolves because selection cannot efficiently eliminate deleterious mutations that manifest themselves only late in life. Under AP, aging evolves as a maladaptive byproduct of selection for increased fitness early in life, with the beneficial early-life effects being genetically coupled to deleterious late-life effects that cause aging. Aging clearly shortens lifespan, but lifespan is also shaped by selection for an increased number of lifetime reproductive events. The evolution of lifespan is therefore a balance between selective factors that extend the reproductive period and components of intrinsic mortality that shorten it. Whether there exist truly immortal organisms is controversial, and recent evidence suggests in fact that aging might be an inevitable property of all cellular life.

Describe how trade-offs between survival and reproduction can result in the evolution of aging.

Life History Trade-Offs and Other Constraints Fitness would obviously be maximal if survival and reproduction would be maximal at all ages, stages, or sizes of an organism. In principle then, the basic problem of life history evolution is trivial: all life history traits should always evolve so as to maximize survival and reproduction and thus fitness (Houle 2001). This would very rapidly lead to the evolution of "Darwinian demons" (Law 1979) that would take over the world, i.e. organisms that start to reproduce as soon as they are born, produce an infinite number of offspring, and live forever. Such organisms, however, do not exist in the real world: Resources are finite, and life history traits are subject to intrinsic trade-offs and other types of constraints, so natural selection cannot maximize life history traits — and thus fitness — beyond certain limits. We call such limits evolutionary constraints (Stearns 1992, Houle 2001); as mentioned above, they represent the intrinsic "boundary condition" we must understand to predict life history evolution. One of the most important types of constraint are life history trade-offs (Stearns 1992, Roff 1992, Flatt and Heyland 2011). A trade-off exists when an increase in one life history trait (improving fitness) is coupled to a decrease in another life history trait (reducing fitness), so that the fitness benefit through increasing trait 1 is balanced against a fitness cost through decreasing trait 2 (Figure 2A). (Note that trade-offs can also involve more than two traits.) At the genetic level, such trade-offs are thought to be caused by alleles with antagonistic pleiotropic effects or by linkage disequilibrium between loci. Trade-offs are typically described by negative phenotypic or genetic correlations between fitness components among individuals in a population (Figure 2A). If the relationship is genetic, a negative genetic correlation is predicted to limit (i.e. to slow down or prevent) the evolution of the traits involved. Thus, a genetic trade-off exists in a population when an evolutionary change in a trait that increases fitness is linked to an evolutionary change in another trait that decreases fitness. The existence of genetic correlations can be established through quantitative genetic breeding designs or through correlated phenotypic responses to selection. For example, direct artificial selection for extended lifespan in genetically variable laboratory populations of fruit flies (Drosophila melanogaster) causes the evolution of increased adult lifespan (sometimes in 10 or fewer generations), but this evolutionary increase in longevity is coupled to decreased early reproduction (e.g., Zwaan et al. 1995). This suggests that lifespan and early reproduction are genetically negatively coupled, e.g. through antagonistic pleiotropic alleles (e.g., Flatt 2011, Fabian and Flatt 2011). At the physiological level, trade-offs are caused by competitive allocation of limited resources to one life history trait versus the other within a single individual, for example when individuals with higher reproductive effort have a shorter lifespan or vice versa (Figure 2B). A helpful way to think resource allocation trade-offs is to imagine a life history as being a finite pie, with the different slices representing how an organism divides its resources among growth, storage, maintenance, survival, and reproduction (Reznick 2010; Figure 2C). The essential problem is this: given the ecological circumstances, and the fact that making one slice larger means making another one smaller, what is the best way to split the pie? Note that since resource allocation trade-offs might have a genetic basis, and since different genotypes may differ in aspects of resource allocation, the genetic and physiological views of trade-offs are not necessarily incompatible. However, physiological trade-offs at the individual level do not always translate into genetic (evolutionary) trade-offs at the population level. For instance, when the physiological (within-individual) trade-off is genetically fixed ("hard-wired") among all individuals within the population, all individuals will exhibit the same negative physiological relationship between two life history traits but the genetic correlation among individuals would be zero (Stearns 1989, Stearns 1992)

Explain the evolution of different life-history strategies.

What is a "life history"? What does your life history look like? In the world of ecology, that question doesn't refer to the many challenges and successes you've experienced, or to the friendships you've made along the way. (Not that those aren't good too!) Instead, when we're talking about life history in ecology, we're thinking about basic demographic features of a population or species - the kind of things that would appear in a life table. That includes when organisms first reproduce, how many offspring they have in each round of reproduction, and how many times reproduction occurs. For humans, life history involves a late start to reproduction, few offspring, and the ability to reproduce multiple times. We can define the life history of a species as its lifecycle, and in particular, the lifecycle features related to survival and reproduction^1 1 start superscript, 1, end superscript. Life history is shaped by natural selection and reflects how members of a species distribute their limited resources among growth, survival, and the production of offspring. Life history strategies and natural selection All living things need energy and nutrients to grow, maintain their bodies, and reproduce. In nature, these resources are in limited supply, and there is often competition for access to them (e.g., to sunlight and minerals for plants or food sources for animals). Thus, each organism will have non-infinite resources to divide among activities like growth, body maintenance, and reproduction. What does it mean for an organism to allocate its limited resources "well" in this context? From an evolutionary standpoint, it means that the resources are distributed among the potential activities (growth, maintenance, reproduction) in a way that maximizes fitness, or the number of offspring the organism leaves in the next generation. Organisms with inherited traits that cause them to distribute their resources in a more effective way will tend to leave more offspring than organisms lacking these traits, causing the traits to increase in the population over generations by natural selection^{2,3} 2,3 start superscript, 2, comma, 3, end superscript. Over very long periods of time, this process results in species with life history strategies, or collections of life history traits (number of offspring, timing of reproduction, amount of parental care, etc.), that are well-adapted for their role and environment. The optimal life history strategy may be different for each species, depending on its traits, environment, and other constraints^{2} 2 start superscript, 2, end superscript. In this article, we'll examine some tradeoffs in life history strategies and see examples of plants and animals that use strategies of different types. Parental care and fecundity One major tradeoff in life history strategies is between number of offspring and a parent's investment in the individual offspring. Basically, this is a "quantity versus quality" question: an organism can have many offspring that each represent a relatively small energy investment, or few offspring that each represent a relatively large energy investment. To put this more formally, we can say that fecundity tends to be inversely related to the amount of energy invested per offspring. Fecundity is an organism's reproductive capacity (the number of offspring it's capable of producing). The higher the fecundity of an organism, the less energy it's likely to invest in each offspring, both in terms of direct resources - such as fuel reserves placed in an egg or seed - and in terms of parental care. Organisms that produce large numbers of offspring tend to make a relatively small energy investment in each, and don't usually provide much parental care. The offspring are "on their own," and the idea is that enough are produced that some will survive (even if the odds for any one are low). Organisms that make few offspring usually make a large energy investment in each offspring and often provide lots of parental care. These organisms are effectively "putting their eggs in one basket" (literally, in some cases!) and are heavily invested in the survival of each offspring. As for so many cases in biology, these are general trends and not universal rules. The main point is just that when organisms have many offspring, they can't invest as much energy in any single offspring. When they have fewer, they can (and must) invest more energy to ensure those offspring's survival. Fecundity and investment tradeoffs in plants The same broad patterns seen in animals also apply to plants. Of course, plants aren't going to provide parental care in the same way that animals do. However, they can still produce either large numbers of energetically "cheap" seeds or small numbers of energetically "expensive" seeds. For example, plants with low fecundity, such as coconuts and chestnuts, produce small numbers of energy-rich seeds, each of which has a good chance of germinating into a new organism. Plants with high fecundity, such as orchids, take the opposite approach: they usually make many small, energy-poor seeds, each of which has a relatively low chance of surviving. Timing of first reproduction (early vs. late) When a species starts reproducing is another important part of its life history—and another place where we see trade-offs and lots of variation among species. Some types of plants and animals start reproducing early, while others delay much longer. What are the pros and cons of these strategies? Organisms that reproduce early have less risk of leaving no offspring at all, but this is may be at the expense of their growth or health. For example, small fish like guppies use their energy to reproduce early in life, but since they throw all their energy to reproduction, they don't reach the size that would give them defense against predators. (An intimidating guppy is kind of hard to picture!) Organisms that reproduce at a later age often have greater fecundity or are better able to provide parental care. On the flip side, they run a greater risk of not surviving to reproductive age. For example, larger fish, like the bluegill or shark, use their energy to grow to a size that gives them more protection. As a consequence, they delay reproduction, so there's more chance that they will die before reproducing (or before they've reproduced to their maximum). In general, age at first reproduction is linked to the lifespan of a species^7 7 start superscript, 7, end superscript. Short-lived species often start reproducing early, while long-lived species are more likely to delay reproduction. This is a good reminder that a life history strategy is an integrated "solution" to the problem of leaving as many offspring as possible, and that any one part (e.g., age of first reproduction) only makes sense in light of others (e.g., lifespan). Single vs. multiple reproductive events Another important characteristic of life history relates to how many times an organism reproduces over its lifetime. For some species, reproduction is a one-time, all-out event, and the organism doesn't survive much beyond that one event. In other species, opportunities for reproduction come around multiple times, or even many times, throughout the organism's lifetime. To apply a little ecology vocab, we can split species into two groups: Those that can reproduce only once (semelparity) Those that can reproduce multiple times over their lifetime (iteroparity) Semelparity In semelparity, a member of a species reproduces only once during its lifetime and then dies. Species with this pattern use up most of their resource budget in a single reproductive event, sacrificing their health to the point that they do not survive. Examples of species that display semelparity are bamboo, which flowers once and then dies, and the Chinook salmon, which uses most of its energy reserves to migrate from the ocean to its freshwater nesting area, where it reproduces and then dies. Iteroparity In iteroparity, individuals of a species reproduce repeatedly during their lives. Iteroparity can take different forms, depending on the reproductive cycles of the organisms involved. Species that display iteroparity don't put all of their resources into a single reproductive event, as there's a fitness benefit (an opportunity to have more offspring) in surviving to reproduce more times. Some animals are able to mate only once per year, but can survive through multiple mating seasons. The pronghorn antelope is an example of an animal that has a seasonal estrus cycle ("heat"). Estrus is a hormonally induced physiological condition that prepares the body for successful mating. Females of species with estrus cycles mate only during the estrus phase of the cycle.