Sci. Aging Knowl. Environ., 26 May 2004
Vol. 2004, Issue 21, p. pe22
[DOI: 10.1126/sageke.2004.21.pe22]

PERSPECTIVES

Declining Immunity with Age in the Wild

Donna Holmes, and Steven Austad

The authors are in the Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA. E-mail: electric{at}uidaho.edu

http://sageke.sciencemag.org/cgi/content/full/2004/21/pe22

Key Words: acquired immunity • antibodies • birds • humoral immunity • parasites

An oft-repeated story among gerontologists--particularly those usually confined to sheltered labs or offices--is that senescence is seldom seen among animals in the wild. At the first hint of physical decay, as the story goes, "nature red in tooth and claw" quickly finishes off the aged, leaving only the young and fit. But to those of us who have spent time in the field--for example, tracking aged opossums showing clear signs of arthritis, cataracts, and infertility, or watching previously virile male elk and pronghorn antelope lose their harems to younger "studs" yet survive for years afterward--this idea comes as a considerable surprise.

Not Dead Yet

It's true that animals in the natural world only rarely live to the advanced stage of decrepitude found in an elderly laboratory mouse grown too feeble to totter across its cage. But to the attentive field biologist, subtle signs of senescence are often apparent and even quantifiable. In a recent article in the Journal of Evolutionary Biology, for example, separate teams of European ornithologists documented reliable aging-related declines in humoral immunity in two different songbird species, the barn swallow (Hirundo rustica) and the collared flycatcher (Ficedula hypoleuca) (1, 2). These two research groups have decades of combined experience monitoring reproduction and other life-history parameters in literally thousands of banded individual birds. Their bodies of work represent some of the more sophisticated attempts among recent efforts by ecologists and field zoologists to incorporate reliable measures of aging into studies focused primarily on mating systems, sexual selection, life-history trade-offs, or other subjects traditionally included in the discipline called "behavioral ecology."

Aging-related physiological declines, including aspects of both innate and acquired immunity, are well documented in laboratory animals and humans [see (3) for a recent SAGE KE Perspective on this topic]. Less well understood, however, are specific fitness deficits associated with advancing age in wild animal populations subject to a full range of natural hazards, such as climatic extremes, infectious disease, and fierce competition for food and mates (4). What can banding and monitoring studies of wild bird populations tell us about aging in nature? In this Perspective we discuss the significance of these two studies, as well as other recent ones that examine wild bird populations to address questions about aging. We also cover some of the pitfalls, as well as the promise, associated with using natural avian populations to test hypotheses about basic mechanisms of aging.

Fly Now, Die Later

The idea that sexually reproducing organisms are forced to perform an evolutionary juggling act, constantly balancing costs and benefits of reproducing immediately against maximizing the chances of survival in order to reproduce in the future, is one of the central tenets of life-history theory (5, 6). The fundamental idea is that populations of small animals, such as wild mice, in which individuals are statistically likely to be killed by cold, starvation, or predators, will be coaxed quickly by natural selection to reproduce (as Chicagoans used to vote) early and often. Animal populations in this menacing, Hobbesian world experience little evolutionary encouragement for investing in the sustained somatic maintenance required for a long, healthy life. On the other hand, animals less vulnerable to environmental hazards, such as those that can fly away from food and water shortages, diseases, and particularly dangerous predators--including swallow, flycatchers, and many bats--should be relatively free of selection pressure to reproduce rapidly. In these cases, natural selection is likely to favor the production of fewer, but higher-quality, young. Young born under this evolutionary regimen will reap the benefits of more parental attention in the form of longer feeding, possible training in foraging techniques, or (as is the case for most biogerontologists) university educations.

Consider this contrast: A wild mouse is born into a litter of five to seven siblings after about 3 weeks' gestation, receives maternal milk for another 3 weeks, and is expected to be on its own, earning a living and reproducing by 2 to 3 months of age. A typical bat, however, is born as an "only child" after a 2-month pregnancy. That youngster may then remain in the nursery colony for 4 to 5 more months, and is not likely to produce its own young for a year or more--an age rarely attained by mice in nature. Songbirds also typically reproduce for the first time at 1 year of age. As a rule, slow-reproducing animals, such as bats and birds, typically also enjoy longer lives and slower aging than do early and frequent reproducers.

As predicted by this evolutionary scenario, maximum documented longevities derived using mark-and-recapture records from migratory bird populations differ substantially from those of small rodents. In many wild populations studied to date, even small songbirds can routinely live more than 6 to 8 years in nature (they survive even longer in the lab) (Fig. 1), whereas mice and rats typically live only a few months in nature and almost never see a second year of life. Bird species that mature and reproduce most slowly (including seabirds, such as albatrosses, terns, and gulls) tend to be among the longest-lived, with some species holding longevity records of more than 75 years.



View larger version (9K):
[in this window]
[in a new window]
 
Fig. 1. Life-spans and approximate lifetime energy expenditures in mice, humans, and some typical birds. c, record from captivity. Data from (7-10). Records for most wild birds are based on banding records from the field and probably underestimate potential life span in captivity. For instance, the longest-lived wild starling was captured at 15 years of age, whereas it lives more than 20 years in captivity. Most longevities were validated using similar values from more than one large sample for a given species. Lifetime energy expenditures were calculated using published estimates of basal or resting metabolic rates. Adapted from (11).

 
Evolutionary biologists also generally assume that, within the life-span of a single organism, the struggle to stay alive and reproduce is energetically costly and inherently risky (12). Risks associated with reproduction probably include the hazards of attracting and competing for mates (for example, greater rates of predation and accident, or reduced foraging ability). Costs presumably include the energetic and biochemical liabilities associated with the production of hormones, noisy songs, flashy ornaments, and nest-building, in addition to spending less time eating and recovering from these other stresses. Increased energy expenditure could also result in a more rapid accumulation of harmful metabolic by-products such as reactive oxygen species, plus compromised immune surveillance against disease or parasites.

Growing Old on the Wing

Birds generally age more slowly than mammals of similar size, despite their higher metabolic rates--but they do age, as these current papers demonstrate. Diseases of aging for birds are well documented by clinical veterinary and zoo data, and are generally similar to those of mammals. For instance, birds develop cardiovascular disease, cancer, cataracts, and arthritis, as well as experience waning fertility. Evidence of senescence in wild bird populations--including flycatchers and swallows--has been mounting steadily since the early 1990s. A number of research groups have reported age-related decreases in survivorship and reproductive success (13-15). Other indications of aging include higher parasite loads in older birds and reduced fitness of offspring produced by aging parents. Survival data gathered on barn swallows and collared flycatchers show one type of evidence for aging: increased death rate (Fig. 2).



View larger version (15K):
[in this window]
[in a new window]
 
Fig. 2. Survival in barn swallows and collared flycatchers, the two bird species featured in the articles under discussion. Solid lines are drawn from the data; dashed lines represent hypothetical age-independent mortality. When survival falls below the dotted lines, it represents an age-related increase in mortality consistent with aging. [Adapted from (17, 18)]

 
Humoral Immunity and Avian Aging: Biogerontology Meets Natural History

The ability of an individual to mount an effective immune response obviously will depend on its overall fitness, which will, in turn, hinge on age, nutritional status, and many other factors. The Saino and Cichon (1, 2) teams each measured slightly different aspects of the humoral component of acquired (also sometimes referred to as "adaptive") immunity (see "Immunity Challenge"). This category of immune responses consists of a suite of relatively delayed but specific defenses against particular pathogens or other antigens, which are then "remembered" in subsequent exposures (1, 2). Humoral immunity consists of the generation of antigen-specific antibodies by B lymphocytes, but also is required for effective responses of some T lymphocytes as well. Humoral or antibody-mediated immune responses defend chiefly against viral and bacterial infections.

One established way to determine the vigor of the humoral response is to challenge the immune system by injecting an antigen (either nonspecific or specific), and subsequently measuring the formation of antibodies. In fact, this is the basis for the use of medical vaccines against certain diseases, such as smallpox. Saino and his colleagues (2) drew small blood samples from individually banded Italian barn swallows of different ages (1- to 5-year-old males and females). They then injected these same birds subcutaneously with a vaccine containing a specific antigen for the virus that causes Newcastle disease (NDV). They monitored the formation of NDV-specific antibodies by collecting blood from as many of these same birds 2 weeks after this "primary" immunization.

The following breeding year, they recaptured and revaccinated as many of these birds as possible, taking blood samples both at the time of this "secondary" vaccination as well as 2 weeks afterward, to measure the secondary immune response. This means that they not only assessed age-related differences in antibody formation in response to the first vaccination, but also the change in antibody titers a year later, both before and after a secondary vaccination.

Barn swallows can live 5 to 7 years in nature, but males generally live longer than females. Both parents participate in feeding nestlings. Regardless of where they were in rearing their young, from incubating to hatching or fledging, and despite the relatively small numbers of birds included in each age group, breeding swallows showed trends toward declining humoral responses--both primary and secondary--with advancing age. These trends were more likely to be statistically significant for females. On average, three-year-old females still mounted a primary antibody response over half that of one-year-old females. Both sex and aging effects were more marked with respect to the secondary response, which was considerably lower overall in females than in males, as were initial antibody titers prior to secondary vaccination the second year of the study. Four-year-old females' secondary responses to NDV vaccination averaged only about a third of those of two-year-olds. As the authors point out, faster immunosenescence in females is consistent with the fact that females invest more time and energy than males in incubating and feeding offspring.

The Cichon (1) group took a slightly different approach to measuring humoral immunity. Focusing only on females, they challenged the immune systems of nesting young, middle-aged, and old birds (1, 3, and 5 to 6 years old, respectively) in their study population on Gotland Island, Sweden, by injecting a suspension of sheep red blood cells (SRBCs) into the peritoneal cavity. SRBC is a standard, nonspecific antigen that is obviously foreign to the avian immune system. Of 79 birds treated in this way, 56 were recaptured 6 days later, and their humoral responses were quantified by measuring hemagglutination, the characteristic clumping of red blood cells that occurs when blood antibodies respond to an antigen.

Their results suggest overall differences between young and old birds, and middle-aged and old birds, but not between young and middle-aged ones. Old females showed antibody titers that were only about half those of younger breeders. A second line of evidence that old birds in the sample were experiencing aging was the trend for old females to have fledglings that were lower in body mass than those of young and middle-aged birds. This probably reflects a decreased maternal ability to provide food for their young in the nest.

A Wild Bird in the Hand: Promises and Pitfalls of Studying Avian Aging in the Field

How important are age-related declines in this type of antibody response to birds in the wild? How much more susceptible to pathogens are birds that mount fewer antibodies to sheep cells or to NDV? Does declining humoral immunity indicate a declining ability of female birds to raise fit offspring late in life? Do the sexes differ over their lifetime in immunocompetence? The two studies we have described here only begin to address these issues. There are still far too few data to address the contribution that physiological deficits, such as blunted immune responses, make to senescence-related mortality in the wild.

In wild animals, seasonal changes in breeding status may be an even more important influence on immunocompetence than are age-related changes. For instance, Lozano and Lank (16) examined cell-mediated immunity in another, longer-lived bird species, the ruff (Philomachus pugnax). These authors measured birds' responses (delayed hypersensitivity) to the mitogenic irritant phytohemagglutinin. Whereas only a marginally significant age-related decline in male cellular immune response was observed, there was a markedly higher response in nonbreeding male ruffs relative to male ruffs monitored during the breeding season, irrespective of age. Male ruffs defend small territories during breeding; hence, the stress of combat could compromise immune function. Cold and food limitation have also been shown to inhibit immunocompetence in other bird species (19, 20). Therefore, environmental stresses may be more important for understanding variation in immune function among wild animals than are the effects of senescence.

The field approach used in the Cichon (1) and Saino (2) studies is one method for longitudinally monitoring aging-related fitness changes under real selective pressures, such as those that promote infectious disease resistance, overall physical condition, reproductive output, and predator avoidance. This approach relies on the ability to quantify and repeatedly measure some biomarker of aging in substantial numbers of wild individuals in a natural setting. The statistical approaches currently used by avian demographers are in many cases robust and sophisticated, taking into account the numerous potential biases inherent in this type of data (such as confounding mortality with failure to return to the study area). Bird studies have other advantages as well: Because birds lay eggs, the effect of reproduction on aging can be experimentally manipulated by transferring eggs from one nest to another.

On the other hand, studies of the effects of aging in wild animal populations have obvious drawbacks for investigating basic mechanisms of aging. The natural habitat of a wild bird is far removed from the cosseted, specific-pathogen-free lives enjoyed by inbred mice in the carefully controlled longitudinal studies of aging favored by most gerontologists. Animals in the wild are subject to the full range of natural diseases and other hazards of living in the wild. This means that intrinsic causes of aging (endogenous physiological declines) will be virtually impossible to distinguish from extrinsic factors (predation or disease, for example). And populations of wild organisms are outbred and extremely variable genetically, further confounding our ability to get a handle on the genetic basis of aging.

What's more, birds of different age classes that survive the stress of experimental treatments may not be representative of a population at large. For some reason, survival rates--the number of birds alive after a specified period of time, divided by the number alive at the beginning of the experiment--in the antigen-challenged swallows in the Saino et al. study (2) were dramatically higher than those of the population as a whole. The longest-lived animals in a wild population have already passed through a significant selective "bottleneck." Their very failure to die means that they have resisted most natural sources of mortality to an exceptional degree, suggesting that they may be genetically exceptional relative to the population at large.

Nonetheless, studies such as those discussed here represent an important link between laboratory biogerontology and natural history. Species that are long-lived for their body size and metabolic rates, such as small birds, may well prove to have special biochemical adaptations for preventing aging-related cellular and molecular damage. Moreover, wild, outbred strains of animals, including rodents and birds, are known in many cases to be longer-lived than their domesticated counterparts. Within a given strain or species, animals live longer in the lab, where they are protected and well fed. However, inbred animals typically are bred for rapid maturation and high fecundity, traits generally correlated with shorter life-spans. For example, wild mouse strains developed by Austad and Miller are significantly longer-lived and slower-aging than inbred C57BL6 laboratory mice (21) (see "Give Me Liberty or Give Me an Early Death"). Ultimately, the discovery of the means of prolonging our own lives may depend, in part, on understanding the molecular basis of longevity in our wild, feathered friends.


May 26, 2004
  1. M. Cichon, J. Sendecka, L. Gustafsson, Age-related decline in humoral immune function in Collared Flycatchers. J. Evol. Biol. 16, 1205-1210 (2003).[CrossRef][Medline]
  2. N. Saino, R. P. Ferrari, M. Romano, D. Rubolini, A. P. Møller, Humoral immune response in relation to senescence, sex and sexual ornamentation in the barn swallow (Hirundo rustica). J. Evol. Biol. 16, 1127-1134 (2003). [CrossRef][Medline]
  3. E. Wollscheid-Lengeling, R.-J. Müller, R. Balling, K. Schugart, Maintaining your immune system--one method for enhanced longevity. Sci. Aging Knowl. Environ. 2004, pe2 (2004).[Abstract/Free Full Text]
  4. R. A. Miller, The aging immune system: primer and prospectus. Science 273, 70-74 (1996).[Abstract/Free Full Text]
  5. G. C. Williams, Pleiotropy, natural selection and the evolution of senescence. Evolution 11, 398-411 (1957). [Abstract/Full Text] [CrossRef]
  6. M. R. Rose, Evolutionary Biology of Aging (Oxford Univ. Press, Oxford, UK, 1991).
  7. R. C. Lasiewski, W. R. Dawson, A re-examination of the relation between standard metabolic rate and body weight in birds. Condor 69, 13-23 (1967).[CrossRef]
  8. P. L. Altman, D. S. Dittmer, Eds., Biology Data Book (Federation of American Societies for Experimental Biology, Bethesda, MD, 1972).
  9. V. M. Gavrilov, V. R. Dolnik, Basal metabolic rate, thermoregulation and existence energy in birds: world data. Acta XVIII Congr. Int. Ornithol. 1, 421-466 (1982).
  10. J. R. Carey, D. S. Judge, Longevity Records: Life Spans of Mammals, Birds, Amphibians, Reptiles, and Fish (Odense Univ. Press, Odense, Denmark, 2002).
  11. D. J. Holmes, M. A.Ottinger, Birds as long-lived animal models for the study of aging. Exp. Gerontol. 38, 1365-1375 (2003).[CrossRef][Medline]
  12. D. A. Roff, The Evolution of Life Histories (Chapman & Hall, New York, 1992).
  13. L. Gustafsson, T. Pärt, Acceleration of senescence in the collared flycatcher Ficedula albicollis by reproductive costs. Nature 347, 279-281 (1990).[CrossRef]
  14. A. P. Møller, F. DeLope. Senescence in a short-lived migratory bird: age-dependent morphology, migration, reproduction and parasitism. J. Anim. Ecol. 68, 163-171 (1999).[CrossRef]
  15. N. Saino, R. Ambrosini, R. Martinelli, A. P. Møller, Mate fidelity, senescence in breeding performance, and reproductive trade-offs in the barn swallow. J. Anim. Ecol. 71, 309-319 (2002).[CrossRef]
  16. G. A. Lozano, D. B. Lank, Seasonal trade-offs in cell-mediated immunosenescence in ruffs (Philomachus pugnax). Proc. R. Soc. London B. Biol. Sci. 270, 1203-1208 (2003).[Medline]
  17. A. P. Møller, T. Szép, Survival rate of adult barn swallows, Hirundo rustica, in relation to sexual selection and reproduction. Ecology 83, 2220-2228 (2002).
  18. L. Gustafsson, personal communication.
  19. M. Hoi-Leitner, M. Romero-Pujante, H. Hoi, A. Pavlova, Food availability and immune capacity in serin (Serinus serinus) nestlings. Behav. Ecol. Sociobiol. 49, 333-339 (2001).[CrossRef]
  20. E. Svensson, L. Råberg, C. Koch, D. Hasselquest, Energetic stress, immunosuppression and the costs of an antibody response. Funct. Ecol. 12, 912-919 (1998).[CrossRef]
  21. R. A. Miller, J. M. Harper, R. C. Dysko, S. J. Durkee, S. N. Austad, Longer life spans and delayed maturation in wild-derived mice. Exp. Biol. Med. 227, 500-508 (2002).[Abstract/Free Full Text]
Citation: D. Holmes, S. Austad, Declining Immunity with Age in the Wild. Sci. Aging Knowl. Environ. 2004 (21), pe22 (2004).








Science of Aging Knowledge Environment. ISSN 1539-6150