The evolutionary theory of ageing explains why ageing occurs, giving valuable insight into the mechanisms underlying the complex cellular and molecular changes that contribute to senescence. Such understanding also helps to clarify how the genome shapes the ageing process, thereby aiding the study of the genetic factors that influence longevity and age-associated diseases.

Why do we age

4. Modelling Survival Data in Medical Research

Evolution of ageing

Bigger animals live longer. The scaling exponent for the relationship between lifespan and body mass is between 0.15 and 0.3. Bigger animals also expend more energy, and the scaling exponent for the relationship of resting metabolic rate (RMR) to body mass lies somewhere between 0.66 and 0.8. Mass-specific RMR therefore scales with a corresponding exponent between -0.2 and -0.33. Because the exponents for mass-specific RMR are close to the exponents for lifespan, but have opposite signs, their product (the mass-specific expenditure of energy per lifespan) is independent of body mass (exponent between -0.08 and 0.08). This means that across species a gram of tissue on average expends about the same amount of energy before it dies regardless of whether that tissue is located in a shrew, a cow, an elephant or a whale. This fact led to the notion that ageing and lifespan are processes regulated by energy metabolism rates and that elevating metabolism will be associated with premature mortality--the rate of living theory. The free-radical theory of ageing provides a potential mechanism that links metabolism to ageing phenomena, since oxygen free radicals are formed as a by-product of oxidative phosphorylation. Despite this potential synergy in these theoretical approaches, the free-radical theory has grown in stature while the rate of living theory has fallen into disrepute. This is primarily because comparisons made across classes (for example, between birds and mammals) do not conform to the expectations, and even within classes there is substantial interspecific variability in the mass-specific expenditure of energy per lifespan. Using interspecific data to test the rate of living hypothesis is, however, confused by several major problems. For example, appeals that the resultant lifetime expenditure of energy per gram of tissue is 'too variable' depend on the biological significance rather than the statistical significance of the variation observed. Moreover, maximum lifespan is not a good marker of ageing and RMR is not a good measure of total energy metabolism. Analysis of residual lifespan against residual RMR reveals no significant relationship. However, this is still based on RMR. A novel comparison using daily energy expenditure (DEE), rather than BMR, suggests that lifetime expenditure of energy per gram of tissue is NOT independent of body mass, and that tissue in smaller animals expends more energy before expiring than tissue in larger animals. Some of the residual variation in this relationship in mammals is explained by ambient temperature. In addition there is a significant negative relationship between residual lifespan and residual daily energy expenditure in mammals. A potentially much better model to explore the links of body size, metabolism and ageing is to examine the intraspecific links. These studies have generated some data that support the original rate of living theory and other data that conflict. In particular several studies have shown that manipulating animals to expend more or less energy generate the expected effects on lifespan (particularly when the subjects are ectotherms). However, smaller individuals with higher rates of metabolism live longer than their slower, larger conspecifics. An addition to these confused observations has been the recent suggestion that under some circumstances we might expect mitochondria to produce fewer free radicals when metabolism is higher--particularly when they are uncoupled. These new ideas concerning the manner in which mitochondria generate free radicals as a function of metabolism shed some light on the complexity of observations linking body size, metabolism and lifespan.

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Body size, energy metabolism and lifespan.

The reliability theory of aging and longevity.

Comparative biology of aging in birds: an update

Bird species are dramatically longer-lived than similar-sized mammals, in spite of two traits--high metabolic rate and elevated blood glucose--which some modern theories of aging suggest should be associated with accelerated senescence. As a consequence of their longevity, birds may possess specialized protective mechanisms against free radical and Maillard reaction damage, and may offer insight into medical interventions for retarding aging. In this review we have highlighted a number of bird species which are commercially available, easily maintained, and more thoroughly characterized with respect to basic physiology than many biogerontologists realize. There seem to us to be few intrinsic barriers to the development of several avian "mice"--extensively characterized species exhibiting exceptionally long life and retarded aging--and for these to become readily accessible as a laboratory resource for the gerontological research community.

Birds as Animal Models for the Comparative Biology of Aging: A Prospectus

The study of post-reproductive lifespan has been of interest primarily with regard to the extended post-menopausal lifespan seen in humans. This unusual feature of human demography has been hypothesized to have evolved because of the “grandmother” effect, or the contributions that post-reproductive females make to the fitness of their children and grandchildren. While some correlative analyses of human populations support this hypothesis, few formal, experimental studies have addressed the evolution of post-reproductive lifespan. As part of an ongoing study of life history evolution in guppies, we compared lifespans of individual guppies derived from populations that differ in their extrinsic mortality rates. Some of these populations co-occur with predators that increase mortality rate, whereas other nearby populations above barrier waterfalls are relatively free from predation. Theory predicts that such differences in extrinsic mortality will select for differences in the age at maturity, allocation of resources to reproduction, and patterns of senescence, including reproductive declines. As part of our evaluation of these predictions, we quantified differences among populations in post-reproductive lifespan. We present here the first formal, comparative study of the evolution of post-reproductive lifespan as a component of the evolution of the entire life history.

Guppies that evolved with predators and that experienced high extrinsic mortality mature at an earlier age but also have longer lifespans. We divided the lifespan into three non-overlapping components: birth to age at first reproduction, age at first reproduction to age at last reproduction (reproductive lifespan), and age at last reproduction to age at death (post-reproductive lifespan). Guppies from high-predation environments live longer because they have a longer reproductive lifespan, which is the component of the life history that can make a direct contribution to individual fitness. We found no differences among populations in post-reproductive lifespan, which is as predicted since there can be no contribution of this segment of the life history to an individual's fitness.

Prior work on the evolution of post-reproductive lifespan has been dominated by speculation and correlative analyses. We show here that this component of the life history is accessible to formal study as part of experiments that quantify the different segments of an individual's life history. Populations of guppies subject to different mortality pressures from predation evolved differences in total lifespan, but not in post-reproductive lifespan. Rather than showing the direct effects of selection characterizing other life-history traits, post-reproductive lifespan in these fish appears to be a random add-on at the end of the life history. These findings support the hypothesis that differences in lifespan evolving in response to selection are confined to the reproductive lifespan, or those segments of the life history that make a direct contribution to fitness. We also show, for the first time, that fish can have reproductive senescence and extended post-reproductive lifespans despite the general observation that they are capable of producing new primary oocytes throughout their lives.

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The Evolution of Senescence and Post-Reproductive Lifespan in Guppies (Poecilia reticulata)

Birds as long-lived animal models for the study of aging.

SYNOPSIS. The long life spans of birds relative to those of mammals are intriguing to biogerontologists, particularly in light of birds' high body temperatures, high blood glucose levels, and high metabolic rates—all of which should theoretically increase their biochemical liability for rapid aging. The comparative longevity of birds and other flying homeotherms is consistent with evolutionary senescence theory, which posits that species with low mortality rates from predation or accident will be released from selection for rapid maturity and early reproduction, and will exhibit retarded aging. Comparative analyses of avian life history parameters to date, although not as extensive as those for mammals, broadly support an association between low mortality rates, slow reproduction, and long lifespan. The diversity of bird life histories suggests the importance of developing a diversity of avian models for studies of aging mechanisms, both proximate and ultimate, and for using wild as well as domestic representatives. Birds studied in the laboratory thus far show many of the same manifestations of aging as mammals, including humans, and many ornithologists are beginning to document actuarial evidence consistent with aging in their study populations. We encourage greater communication and collaboration among comparative gerontologists and ornithologists, in the hope that the study of aging in birds will lead to an integrated understanding of physiological aging processes well grounded in an evolutionary paradigm.

Donna J. Holmes

Papers

Comparative biology of aging in birds: an update

Birds as Animal Models for the Comparative Biology of Aging: A Prospectus

The Evolution of Senescence and Post-Reproductive Lifespan in Guppies (Poecilia reticulata)

Birds as long-lived animal models for the study of aging.

The evolution of avian senescence patterns : implications for understanding primary aging processes