Since , lifespans have doubled again, largely due to improvements in environment, food, and medicine that minimized mortality at earlier ages. Infections cause most mortality in wild chimpanzees and in traditional forager-farmers with limited access to modern medicine. Although we know little of the diseases of aging under premodern conditions, in captivity, chimpanzees present a lower incidence of cancer, ischemic heart disease, and neurodegeneration than current human populations.
These major differences in pathology of aging are discussed in terms of genes that mediate infection, inflammation, and nutrition. Humans have the longest life spans of any primate. Even under the conditions of high mortality experienced by hunter-foragers, the human life expectancy at birth LE 0 is twice that of wild chimpanzees. This inquiry considers the demographics and pathology of aging in humans and great apes as an approach to understanding how aging processes evolved with longer lifespans. I argue that immune functions and nutrition have been of major importance in the evolution of aging and longevity.
The human LE 0 has doubled during over an evolutionary span of about , generations from a great ape ancestor shared with chimpanzees 1 , 2. The lifespans of intermediate species during human evolution cannot be known, because the spotty skeletal evidence at hand allows only general estimates of age classes.
According to tooth wear, early modern H. Turning from the huge gap before historical times, we may model earlier H. Both lived under unhygienic conditions with high burdens of infection and limited access to effective medicine. Despite low survival, half of those reaching age 20 reached 60 LE 20 of 40 years.
Mortality across the lifespan forms a J-shaped curve in most mammalian populations: Humans differ from wild chimpanzees by their lower mortality in juvenile and adult ages, and by the later onset of mortality rate acceleration 6 , 8 , 11 Fig. In healthy populations of humans and lab animals, the acceleration of mortality is preceded by increasing morbidity from chronic degenerative disease 2 , The chimpanzee life expectancy at birth LE 0 is about 13 years, whereas those reaching adulthood age 15 have about 15 years of further life expectancy 6 , 11 Table 1.
Very few have survived beyond age 50, even in captivity with modern veterinary care Two key factors in human life expectancy are the delayed mortality rate acceleration and lower q min Fig. The q min merits attention in human evolution As discussed later, this apparent species difference may be due to stronger immune responses.
Since , the industrialized countries have further lowered q min by fold Demographic comparisons of wild chimpanzees with human populations living under poor hygiene and with little access to medicine. At all ages after infancy, chimpanzees have higher mortality than the Ache and show acceleration of mortality at least 20 years earlier. There is frustratingly little information on diseases of aging in wild chimpanzees and in hunter-foragers for comparison with modern populations.
The following summary necessarily includes individual observations as well as larger studies. The main cause of mortality throughout human evolution until the 20th century must have been infections, as observed in wild chimpanzees and 20th-century hunter-foragers.
The oldest individuals frequently had prolonged diarrhea 16 , p Infected wounds from accidents or fighting were also a common secondary cause of death see note to Table 2. The accelerating mortality rates of chimpanzees soon after age 20 Fig. The Gombe chimpanzees cannot be considered a pristine population because of their exposure to pathogens from local humans and domestic animals e. There may be no remaining truly isolated chimpanzee population in which to evaluate pathogen loads and mortality causes, because of increased commercial activity and warfare.
There is no detailed profile of native infectious agents in any wild primate population These human populations, although relatively isolated, also had tuberculosis and other pathogenic infections 7 that are unlikely to have been indigenous Notably unlike chimpanzees, a definitive proportion of elderly forager-farmers age 60 or older died from nonspecific senescent causes. Before the 18th century, there are no national or regional statistical data on mortality rates by age group or causes of death.
In the ancient Greco-Roman world, demographic reconstructions agree on short LE 0 ranging 20—35 years 21 , It may be concluded that few in this era lived longer than 90 years, which is the upper age limit validated in hunter-gatherer-foragers 6 , 7.
Contagious infections and septic wounds are likely to have been the major causes of death in ancient populations living under unsanitary conditions 2 , 21 , The high incidence of infectious causes of death among 20th-century hunter-gathers resembles preth-century populations, where infections, directly or indirectly, were major causes of adult deaths. Almost all deaths before age 5 were due to infections 9 , 24 , The much lower q min for humans than chimpanzees Table 1 suggests corresponding differences of immunological functions, as described later.
Data on cause of death for juvenile ages are needed to evaluate the contribution to mortality from transmissible infections, septic wounds from in-group aggression and accidents, and from predation to which subadults are more vulnerable by smaller size and lack of experience. Exposure to chronic infections and inflammation has major ramifications for aging processes through 2 main fronts: Because HIV is associated with accelerated memory T-cell accumulation and frailty 29 , it is predicted that immunosenescence will be accelerated in the hunter-gatherers with high infectious loads Table 2.
The associations of high early mortality and shorter life expectancy in historical populations give important clues to early human evolution in highly infectious environments. Crimmins and I examined Sweden and several other 19th-century European populations that had high early age mortality from infections. The correlations of mortality before age 5 with mortality at age 70 were much stronger for birth cohorts than for the periods 5 , We proposed a "cohort morbidity hypothesis" in which survivors of early infections carried higher inflammatory loads, which promote chronic diseases with inflammatory components, such as cardiovascular disease.
Atherosclerosis, for example, begins before birth, with accumulating lipids, monocytes, and local oxidative damage; "fetal programming" from maternal diet, cholesterol, and stress can influence the later progression of arterial degeneration 2 , 30 , Higher mortality of elderly to infections could also be involved in cohort effects, e. The progressive reduction of mortality at later ages in birth cohorts with better early survival is likely to involve complex interactions of atherosclerosis and immunity 2.
To further evaluate relationships between infectious exposure and accelerated aging, we examined the U. Most deaths were secondary to bacterial infections that caused severe pneumonia. This population was considered well-nourished, unlike earlier European cohorts.
Specific prenatal influences were found on later aging: Moreover, the birth cohort had lower educational achievement and was slightly shorter at WWII enlistment. Because influenza rarely invades the placenta or fetus, these effects may involve stress effects on the fetus with elevations of maternal cortisol and IL-6, and imprinting of the fetal genome reviewed in ref. Apparently, even brief maternal infections without malnutrition impair postnatal growth and accelerate cardiovascular aging.
These findings also extend the Barker theory of developmental origins of adult diseases of aging to effects of stress on the fetus from maternal infections. We cannot know the incidence of arterial disease or cancer in preth-century populations because there are no population-based clinical data.
Nonetheless, there are indications of arterial diseases in early historical human populations. For arterial disease, the oldest case is the Tyrolean iceman from 5, years ago, who died accidentally at about age 45; CT imaging showed calcification of both carotid arteries and portions of aorta and iliac artery In modern populations, arterial calcification is a high risk marker for vascular fatal events, with 4-fold more mortality in the following decade 36 , Though these scattered samples cannot inform about the prevalence of atherosclerosis in historical populations or its contribution to mortality, they suggest that advanced atherosclerosis is not a modern condition.
For chimpanzees, the only histopathological data are from captives, which in earlier decades were exposed to varying conditions of husbandry and diet, including dairy products, which are not normal for wild chimpanzees. Up thru , arterial fatty degeneration and sudden death from heart attack or stroke were widely noted as comparable to humans, as represented in these examples from a scattered literature 1.
These levels would be considered high risk for cardiovascular events in humans. Subsequent well-maintained colonies on more standardized diets are puzzlingly divergent for blood lipids: Other cardiovascular risk indicators included elevated fibrinogen, insulin, and Lp a ; the latter is a species difference, due to increased transcription of the Lp a gene Markers of oxidation in blood-cell DNA and lipids were higher, though some antioxidants were lower relative to healthy young men.
Despite these risk indicators, ischemic coronary artery disease has not been identified as the main cause of death in 3 other modern colonies, where most sudden deaths were attributed to congestive heart failure from fibrillation in association with myocardial fibrosis: Yerkes 44 , Almagordo 47 , and Southwest Foundation Ischemic arterial disease was considered minor in most sudden deaths in these well-maintained colonies, in contrast to the earlier reports. However, myocardial fibrosis was also common in early colonies 40 , Female chimpanzees from Yerkes and Southwest Foundation had more neoplasia than males, with notable prevalence of uterine leiomyomas The leiomyomas and most other tumors were benign and arose after age Remarkably, no spontaneous mammary carcinoma has been reported in the great apes.
In males 25 years and older, benign prostatic hyperplasia is common, and associated with clinical-grade blood prostate-specific antigen and urinary retention Though prostate neoplasia was not reported 52 , 54 , later ages need study. Other primate species also present a low incidence of neoplasia. In view of the absence of mammary carcinoma in chimpanzees, the documentation of mammary carcinoma in prosimians and monkeys references in ref.
Provisionally, primate colonies have lower prevalence of malignancy than most modern human populations, e. However, the above studies did not present data on the population at risk by age, needed for comparison with human populations. The surviving aging great apes are a vanishing resource because active breeding has been stopped in U. The absence of pregnancy also eliminates a protective factor for breast cancer in humans.
There may be no way to obtain autopsy data on wild populations without supporting the bushmeat trade. The paleopathology of neoplasia may only be approached in bone tumors, which persist in graveyard and fossil skeletons I have not found reports on pathologically confirmed bone tumors in prehistoric human fossils. The neuropathology of aging in great apes is also surprising. Detailed studies of brains from chimpanzee, gorilla, and orangutan of 40 years or older concur on the rarity of Alzheimer-like neurodegenerative changes of neuronal loss, neuritic plaques dense amyloid plaques with neuritic degeneration , and neurofibrillary degeneration with tau immunoreactivity 1 , 64 , Nonetheless, it was recent reported that a year-old chimpanzee died after a stroke with the classic tau-positive neurofibrillary tangles with paired helical filaments This individual also had obesity and chronic hypercholesterolemia.
Despite the neurofibrillary tangles, other brain changes were mild: Possibly, hypercholesterolemia may promote a subset of Alzheimer-like changes in chimpanzees under some circumstances. Variations of trace elements could be a factor. Lead can also promote later formation of amyloid deposits in monkeys Wild chimpanzees of 25 years have increasingly frequent decrepit appearances from bone fractures, skin wounds, tooth loss, weight loss, and difficulty climbing 16 , p Degenerative osteoarthitic changes are indicated in some samples.
Similarly, an early 20th-century sample from West Africa had prevalent erosive osteoarthritis A Gombe sample, however, had minimal spinal osteoarthritis The uncertain ages and small samples preclude comparisons with humans. Nonetheless, wild females are fertile up through at least 42 years Thus, few if any female chimpanzees survive to reproductive senescence in natural populations.
By contrast, most hunter-gatherer females reaching adulthood survive beyond menopause 6 , 8 , 9. The extended postmenopausal phase also uniquely exposes humans to osteoporotic fractures from low estrogen that are not reported for great apes. Male reproductive aging is undefined: The social hierarchies that determine access to females are dominated by prime-age adult males typically in the late teens to late twenties 16 , fig.
The indications of faster aging in chimpanzees than in humans by the earlier acceleration of mortality require corroboration by age-specific changes in pathology and organ function. Because menopause occurs at about the same age, 50, reproductive declines may be relatively delayed in female chimpanzees.
The emerging profile of pathology in aging captive chimpanzees suggests the importance of environmental and husbandry variables for myocardial and brain aging, in which blood cholesterol and trace metals could be important. The low prevalence of ischemic heart disease in modern colonies may represent improvements of husbandry, but the scattered data from earlier colonies do not allow firm conclusions.
However, for cancer and myocardial pathology, age-specific rate data are needed for comparison with human aging. Measures of cardiopulmonary function and immunosenescence in captive colonies will also be informative. Conversely, it is important to know whether the diffuse interstitial fibrosis of aging chimpanzees also occurs in some human populations. During human evolution, the diet has shifted to increased consumption of animal tissues, although plant-based foods have always been important 1 , 2 , The advantages of meat-rich diets include higher density caloric content reducing efforts in foraging and digestion , and concentrated micronutrients trace metals and polyunsaturated fatty acids required for optimum development of the musculature and nervous system.
However, increased trace metals and fat ingestion could also interact with pathogensis, as noted previously. The greater meat consumption of longer-lived humans than great ape ancestors presents a paradox because in many animal models of human disease and longevity, greater fat and caloric intake is associated with accelerated pathogenesis and shortened lifespan 1 , 2.
Similarly, caloric restriction attenuates atherosclerosis, diabetes, and neoplasia in animal models 2. Changes in diet also increased exposure to pathogens and toxins. Uncooked meat, particularly from scavenged old carcasses, would have increased exposure to infectious pathogens. Though cooking can kill most pathogens and increases the digestibility of meat and fibrous plant material 79 , cooking also accelerates nonenzymatic glyco-oxidation to form advanced glycation endproducts AGEs that are diabetogenic and proatherosclerotic in animal models and in clinical studies 80 , How did humans evolve increased longevity despite the greater fat intake and exposure to pathogens?
Finch and Stanford 1 proposed that the diet and longevity shifts during the evolution were supported by meat-adaptive genes, with tradeoffs of mortality and for ingestion of fat and toxins, and pathogen exposure. Before considering specific genes, it is notable that a small part of the DNA difference between humans and chimpanzees shows evidence of positive selection.
Evolving Demographics of Aging The human LE 0 has doubled during over an evolutionary span of about , generations from a great ape ancestor shared with chimpanzees 1 , 2. Evidence for a developmental origin and environmental link for AD. Mortality across the lifespan forms a J-shaped curve in most mammalian populations: American Cancer Society, Refresh and try again.
The genome-wide single nucleotide nt differences are 1. Genes undergoing positive selection based on the ratio of nonsynonymous: Moreover, genes associated with immunity and brain have variation clusters of highly localized groups of changes in coding regions Surprisingly, the aging-associated genes had less variation than the average, implying slower evolutionary change in the human lineage, e. The high incidence of neoplasia in humans is not explained so far by DNA sequences.
Of cancer-associated genes, the majority are almost identical in chimpanzees 88 , BRCA1 also shows evidence for positive selection at the coding level and Hardy-Weinburg disequilibrium in human populations. Influences of BRCA1 and - 2 alleles on early growth imply tradeoffs for growth and DNA repair relevant to the uniquely human pattern of early breast development with antagonist pleiotropy of later neoplasia Host defense system genes show evidence for positive selection, as noted. The most details may be available for the major histocompatibility complex MHC and sialic acid-binding Ig-like lectins Siglecs.
The MHC system is fundamental to innate and adaptive immunity: A major species difference is the loss of polymorphisms in class I A and B genes. Because the remaining MHC classes had equivalent variety, this class-specific loss of variation suggests a selective sweep There is no easy test of the adaptiveness of the numerous allele differences.
Differences in the Siglec lectin family of proteins Ig superfamily cell-surface glycoproteins have specific implications for host-defense evolution in studies from Varki and coworkers 92 , Siglecs bind the sialic acids on cell surfaces of macrophages and other immune-related cells. Siglec genes appear to have evolved very rapidly, because there is a much smaller divergence between mice and rats, which had a more distant common ancestor. Siglec-5 manipulation switched the species-type response to T-cell receptor TCR stimulation.
This species difference may be a factor in T-cell-mediated diseases, including the much milder chimpanzee disease from HIV-1 and hepatitis B or C 94 , and the apparent lack of spontaneous rheumatoid arthritis and bronchial asthma. These differences in immunoreactivity could involve the weaker expression of CD33rSiglecs of humans, relative to great apes Siglecs also modulate Streptococcus invasiveness GBS Direct species comparisons are needed of immune cell responses to specific pathogens and of transcriptomes and kinomes.
Humans also differ by the absence of N -glycolylneuraminic acid Neu5Gc , a major sialic acid of chimpanzees and other great apes 92 , A mutation that occurred early in the genus Homo , at least before 0. For example, the chimpanzee malarial parasite has a protein that binds preferentially to Neu5Gc during erythrocyte invasion, whereas that of the human parasite P. The evolving human diet could also have had a role in these complex immunological scenarios, because normal tissues have traces of Neu5Gc, which may be acquired from ingestion of red meat and milk; this could stimulate chronic inflammation induced by anti-Neu5Gc antibodies and also facilitate metastasis Lastly, I consider the apolipoprotein E ApoE alleles, which modulate chronic inflammation and many aspects of aging in brain and arteries and which Sapolsky, Stanford, and I 1 , 2 , 98 have proposed as a meat-adaptive candidate gene in the increases of the human lifespan.
Blood apoE mediates the clearance of triglyceride-rich lipoprotein components, and brain apoE transports cholesterol to neurons The uniquely human apoE3 allele spread about 0. These dates precede the emigration of modern H. In general, the apoE4 allele shortens lifespan by several years and accelerates degenerative changes in arteries and brain 2 , 99 , , , ApoE4 carriers have modestly higher total blood cholesterol, more oxidized blood lipids, and greater risk of coronary heart disease ca.
ApoE4 carriers also have worse outcomes in traumatic brain injury and some neurological conditions. One mechanism may involve heightened inflammatory responses. On a fatty diet, TR- apoE4 mice had larger adipocytes and impaired glucose tolerance ; however, obesity and diabetes have not shown consistent apoE allele associations.
Though the chimpanzee apoE has 2 amino acids like apoE4, it is predicted to function like the human apoE3 isoform because of a further coding difference that influences peptide folding , Table 3. Although chimpanzee apoE has not shown allelic variation in small samples , serum cholesterol had considerable heritability in a former breeding colony Besides influencing brain aging, apoE alleles also affect brain development. Cortical neurons of young TR- apoE4 mice have less dendritic complexity , which may be a factor in their impaired spatial memory ApoE alleles are increasingly included in studies of human development.
In MRI studies of healthy juveniles, the apoE4 carriers had a thinner entorhinal cortex As a hedge against overinterpretations of these broad effects, it may be reassuring that apoE alleles have not shown consistent associations with fertility or neoplasia 2. Given these adverse effects of apoE4 , at least in modern environments, the persistence of the allele has been proposed as the result of balancing selection, as in malarial protection by heterozygotes of hemoglobinopathies 1 , Two examples are under discussion, for which the evidence must be considered as preliminary.
In hepatitis C infections, apoE4 carriers incurred less fibrotic damage by allele dose , , whereas Brazilian slum children carrying apoE4 showed less diarrhea and associated impairments of cognitive development , Want to Read Currently Reading Read. Refresh and try again. Open Preview See a Problem?
Thanks for telling us about the problem. Return to Book Page. The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans 3. Inflammation, Nutrition, and Aging in the Evolution of Lifespans synthesizes several decades of top research on the topic of human aging and longevity particularly on the recent theories of inflammation and its effects on human health.
The book expands a number of existing ma Written by Caleb Finch, one of the leading scientists of our time, The Biology of Human Longevity: The book expands a number of existing major theories, including the Barker theory of fetal origins of adult disease to consider the role of inflammation and Harmon's free radical theory of aging to include inflammatory damage. Future increases in lifespan are challenged by the obesity epidemic and spreading global infections which may reverse the gains made in lowering inflammatory exposure. This timely and topical book will be of interest to anyone studying aging from any scientific angle.
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