Humans have evolved two traits that differ from other great apes and that appear to be antagonistic: slower aging despite a major increase in meat eating. The three great apes - chimpanzees, gorillas, and orangutans - and the gibbons do not live more than 60 years under the best circumstances. The longevity of humans evolved despite the higher exposure to cholesterol and other fats than in other great apes. Laboratory chimpanzees are highly sensitive to dietary fat, which causes hyperlipidemia, accelerated vascular disease, and rapid increases in myocardial infarcts. Furthermore, clinical and animal studies indicate that blood cholesterol is a risk factor in Alzheimer Disease. We conclude that the evolution of "meat-adaptive genes" was crucial to the evolution of human longevity. The hominoid lineage has been mainly vegetarian for more than 25 million years, according to evidence from dentition and the current diet of great apes. The gorilla and bonobo feed almost exclusively on fruit, leaves, and nuts. The chimpanzee is a partial exception, because some individuals hunt and eat other small mammals. However, other individuals, as well as neighboring groups, may not eat meat. During the past several million years, meat eating increased progressively, more - or less in concert with increases of brain size, longer postnatal care, and increasingly sophisticated tool manufacture and hunting strategies. Stone-age hunters clearly targeted brains and bone marrow, which provide year-around sources of fat that are used to metabolize protein. Limitations on dietary fat or carbohydrate restrict the amount of muscle that can be eaten without inducing ammonia toxicity because of the ceiling on urea production. Humans are clearly adapted to consume much more meat for energy than, for example, chimpanzees, which forage in 90 % smaller areas than present hunter-gatherers. The increased life expectancy is of particular importance to those aged 20-50, when most human hunter-gatherers are their most productive. The increase of dietary fat would be expected to select for meat-adaptive genes that reduce hyperlipidemia with associated risks to heart and brain. A rapidly emerging literature is consistent in the ability of elevated cellular cholesterol to increase production of the amyloid beta-peptide. There are also indications that elevated neuronal cholesterol is associated with NFT formation, particularly in Nieman-Pick disease, a cholesterol storage disorder. The apoE allele system could be important, because primates have only the E4 allele, which promotes higher blood cholesterol and increased risk of vascular disease and AD. The apoE4 isoform is relatively vulnerable to cleavage into a fragment that causes tau-hyperphosphorylation. Other genes may increase host resistance to infectious agents in uncooked organs (viruses and prions found in marrow and brain; enteric parasites). Muscle is also rich in metals (heme-iron, copper and zinc), which would involve genes of detoxification. It is clear that the evolution of meat-adaptive genes was required for human longevity. These adaptations also pose questions about the applicability of caloric restriction to health and aging in normal humans, i.e., those without obesity who exercise. More generally, some racial groups show different incidence of AD between national populations, which may involve the degree of vegetarianism. Thus, pursuit of evolutionary questions may also give important insights into human risk factors.
