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Evolution of the Human Lifespan and Diseases of Aging: Roles of Infection, Inflammation, and Nutrition

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Evolution of the Human Lifespan and Diseases of Aging: Roles of Infection, Inflammation, and Nutrition Evolution of the human lifespan and diseases of aging: Roles of infection, inflammation, and nutrition Caleb E. Finch1 Davis School of Gerontology and the University of Southern California, Los Angeles, CA 90089 Edited by Stephen Curtis Stearns, Yale University, New Haven, CT, and accepted by the Editorial Board October 12, 2009 (received for review August 25, 2009) Humans have evolved much longer lifespans than the great apes, 11) (Fig. 1). In healthy populations of humans and lab animals, which rarely exceed 50 years. Since 1800, lifespans have doubled the acceleration of mortality is preceded by increasing morbidity again, largely due to improvements in environment, food, and med- from chronic degenerative disease (2, 10). For wild chimpan- icine that minimized mortality at earlier ages. Infections cause most zees, typical early mortality rates are 20% per year in infancy, mortality in wild chimpanzees and in traditional forager-farmers within the range of hunter-gatherers, then decreasing to a qmin with limited access to modern medicine. Although we know little of about 3.5% per year in preadult ages. The chimpanzee life of the diseases of aging under premodern conditions, in captivity, expectancy at birth (LE0) is about 13 years, whereas those chimpanzees present a lower incidence of cancer, ischemic heart reaching adulthood (age 15) have about 15 years of further life disease, and neurodegeneration than current human populations. expectancy (6, 11) (Table 1). Very few have survived beyond age These major differences in pathology of aging are discussed in 50, even in captivity with modern veterinary care (13). In con- terms of genes that mediate infection, inflammation, and nutrition. trast, human mortality after the early years is much greater, with Apolipoprotein E alleles are proposed as a prototype of pleiotropic >2-fold longer LE0 and >3-fold lower qmin, even with limited fl ’ genes, which in uence immune responses, arterial and Alzheimer s access to medicine (Table 1). Since 1800, the LE0 in developed disease, and brain development. nations rose progressively to >70 years. Only recently has sur- vival to >90 been well documented; currently, centenarians are chimpanzee | pathology about 0.01%–0.02% in developed nations (14). Two key factors in human life expectancy are the delayed mortality rate accel- umans have the longest life spans of any primate. Even under eration and lower qmin (Fig. 1). The qmin merits attention in the conditions of high mortality experienced by hunter- human evolution (10): even in populations with high infectious H burdens and neonatal mortality, the human q is >50% lower foragers, the human life expectancy at birth (LE0) is twice that of min wild chimpanzees. This inquiry considers the demographics and than wild chimpanzees (Table 1). As discussed later, this appa- pathology of aging in humans and great apes as an approach to rent species difference may be due to stronger immune re- understanding how aging processes evolved with longer life- sponses. Since 1800, the industrialized countries have further spans. I argue that immune functions and nutrition have been of lowered qmin by 25-fold (12). major importance in the evolution of aging and longevity. Causes of Mortality. There is frustratingly little information on Evolving Demographics of Aging diseases of aging in wild chimpanzees and in hunter-foragers for comparison with modern populations. The following summary The human LE0 has doubled during over an evolutionary span of about 300,000 generations from a great ape ancestor shared with necessarilyincludesindividual observations aswell aslargerstudies. chimpanzees (1, 2). Then during the last 200 years during in- Infections. The main cause of mortality throughout human evolu- tion until the 20th century must have beeninfections, asobserved in dustrialization and in <10 generations, the LE0 has doubled again (3, 4), allowing major increases in older ages. The lifespans of wild chimpanzees and 20th-century hunter-foragers. Longitudinal intermediate species during human evolution cannot be known, studies of the Gombe chimpanzees (Tanzania) since 1960 by Goodall and colleagues identified infections in the majority of because the spotty skeletal evidence at hand allows only general deaths (67%) for all ages (Table 2) (15). The oldest individuals estimates of age classes. According to tooth wear, early modern frequently had prolonged diarrhea (16, p 104). Infected wounds H. sapiens and H. neanderthalensis had a larger proportion of from accidents or fighting were also a common secondary cause of older adults than prior Homo species and Australopithecus (5). death (see note to Table 2). The accelerating mortality rates of Turningfrom thehugegapbeforehistorical times,wemaymodel chimpanzees soon after age 20 (Fig. 1) implies decreasing resist- earlier H. sapiens demographics by preindustrial populations for ance to infections with aging, as well as synergies of infections with which there is good demographic data: Sweden from 1751 (3, 4) other myocardial damage, discussed below. and 20th-century hunter-foragers (6–8). Both lived under un- The Gombe chimpanzees cannot be considered a pristine pop- hygienic conditions with high burdens of infection and limited ulation because of their exposure to pathogens from local humans access to effective medicine. Their high mortality at early ages of and domestic animals (e.g., mange, polio, and tuberculosis). A 10%–30% restricted the LE to 30–40 years. Despite low survival, 0 recent SIVcpz infection (chimpanzee-derived simian immuno- half of those reaching age 20 reached 60 (LE of 40 years). Thus, 20 deficiency virus) has been transmitted vertically and horizontally, most hunter-gatherers survive beyond menopause, unlike wild with >10-fold higher mortality in carriers and lower fertility and chimpanzees (7–9). The greater survival to later ages allowed the evolution of stable multigenerational support of the young, a uniquely human trait among primates (7–9). This paper results from the Arthur M. Sackler Colloquium of the National Academy of Mortality across the lifespan forms a J-shaped curve in most Sciences, “Evolution in Health and Medicine” held April 2–3, 2009, at the National Academy mammalian populations: the high early age mortality declines to a of Sciences in Washington, DC. The complete program and audio filesofmostpresentations minimum (qmin) at the approach of adulthood, followed at are available on the NAS web site at www.nasonline.org/Sackler_Evolution_Health_Medicine. midlife by exponential accelerations of mortality in association Author contributions: C.E.F. wrote the paper. with increased chronic degenerative disease and dysfunctions The authors declare no conflict of interest. that collectively define senescence (2, 10). Humans differ from This article is a PNAS Direct Submission. S.C.S. is a guest editor invited by the wild chimpanzees by their lower mortality in juvenile and adult Editorial Board. ages, and by the later onset of mortality rate acceleration (6, 8, 1To whom correspondence should be addressed. E-mail: cefi[email protected]. 1718–1724 u PNAS u January 26, 2010 u vol. 107 u suppl. 1 www.pnas.org/cgi/doi/10.1073/pnas.0909606106 Downloaded by guest on September 26, 2021 100 deaths. In national data for England and Wales of 1861, for Ache example, infections caused 25% of female deaths before age 40 90 Hadza (24). Almost all deaths before age 5 were due to infections (9, 24, 80 Hiwi 25). The much lower qmin for humans than chimpanzees (Table 1) 70 )%( s )%( !Kung suggests corresponding differences of immunological functions, 60 as described later. Data on cause of death for juvenile ages are r Chimp ovivruS 50 needed to evaluate the contribution to mortality from trans- missible infections, septic wounds from in-group aggression and 40 accidents, and from predation to which subadults are more vul- 30 nerable by smaller size and lack of experience. 20 Exposure to chronic infections and inflammation has major fi 10 rami cations for aging processes through 2 main fronts: immu- nosenescence and synergies with chronic diseases that have 0 fl 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 in ammatory components. In brief, immunosenescence involves Age depletion of the limited pool of naïve T cells acquired during maturation. During antigenic exposure across life, the pool of − memory T cell (CD8+ CD28 T cells) increases progressively, at 22 Ache F least in part from antigenic stimulation by common infections e.g., 20 CMV, HSV, influenza (2, 26–28). A subgroup of elderly with the Ache M 18 “immune risk” phenotype for higher mortality have relative de- + 16 Chimp F pletion of CD28 T cells and memory T cells with telomere ero- )Y/%( ytilatroM launnA ytilatroM )Y/%( sion, increased cytokine expression, and other markers of cellular 14 Chimp M immunosenescence. Because HIV is associated with accelerated 12 memory T-cell accumulation and frailty (29), it is predicted that 10 immunosenescence will be accelerated in the hunter-gatherers 8 with high infectious loads (Table 2). 6 The associations of high early mortality and shorter life 4 expectancy in historical populations give important clues to early human evolution in highly infectious environments. Crimmins and 2 I examined Sweden and several other 19th-century European 0 populations that had high early age mortality from infections. The 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 correlations of mortality before age 5 with mortality at age 70 were Age much stronger for birth cohorts than for the periods (5, 25). We proposed a "cohort morbidity hypothesis" in which survivors of Fig. 1. Demographic comparisons of wild chimpanzees with human pop- early infections carried higher inflammatory loads, which promote ulations living under poor hygiene and with little access to medicine. [Re- chronic diseases with inflammatory components, such as car- produced with permission from ref. 6 (Copyright 2000, John Wiley & Sons).] fi diovascular disease. Atherosclerosis, for example, begins before (A) Survival curves.
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