Unexpected mechanisms make us live longer and also make us sick in old age
Why do humans live longer than other primates? The traditional view is that this is due to the development of modern medicine, adequate food, and advanced health systems. However, new research shows that although the above factors have prolonged human life in the last 200 years, the tendency of human beings to live longer than other primates has existed long before. When human ancestors began to ingest more meat, they gradually evolved immune mechanisms against germs in the meat. These immune mechanisms prolong the lifespan of humans, but they also make humans pay a high price, making humans more susceptible to some diseases of the elderly in their later years.
Compared with other primates, we humans have abnormally long lives. For example, chimpanzees, the extant living species that have the closest relationship with us, have an average life expectancy at birth of only about 13 years; while infants born in the United States in 2009 have a life expectancy of 78.5 years. Why human life is much longer than other primates?
Many researchers have attributed our long life to the invention of vaccines, antibiotics, and efficient urban health systems and fresh and nutritious fruits and vegetables that are continuously available throughout the year. A lot of demographic evidence also shows that over the past 200 years, these factors have greatly prolonged human life. But Caleb Finch, a biologist at the University of Southern California in the United States, believes that the above factors, while important, are only part of the mystery of human longevity. He collected data from many disciplines including physical anthropology, primatology, genetics, and medicine, and proposed a controversial new hypothesis: The trend of human aging slowdown and longevity has long begun because of the advancement of our ancestors. A defense system that can fight various pathogens and harmful substances in the ancient environment.
If Vinci is correct, then the future research on the complex relationship between infectious diseases, host defenses, and chronic diseases of the elderly may well subvert scientists’ understanding of aging and find solutions to deal with aging.
The evolution of longevity
A study of modern hunter-gatherers shows that modern medicine and a rich food supply are not the only reason for human longevity. In 1985, Nicholas Blurton-Jones, a biological anthropologist at the University of California, Los Angeles, and an assistant drove to the isolated camp of Hadza in Tanzania. The Hazara is a nation that uses hunting and gathering to make a living. Like their ancestors, they hunt quail and wildebeests and feed on starchy roots. During the rainy season, they collect honey from the bees of African bees.
Modern hunter-gatherers, such as the Hazara in Tanzania, live in a natural environment full of parasites and germs like chimpanzees, but they live far longer than chimpanzees. This may be because humans have evolved adapted to meat. The genes.
The two researchers visited each local tent and collected basic demographic data such as the name and age of each family member. In the next 15 years, they updated these statistics again six times and recorded the names and causes of death of all the dead. In addition, Bretton-Jones also obtained some of the earlier Hazard statistics from two other researchers.
Like primitive humans and chimpanzees, the Hazara live in a natural environment full of germs and parasites. They do not have running water or a sewer system. They defecate in an area 20 to 40 meters away from the tent and do not understand medical treatment. But Breton-Jones found that the life of the Hazar was far longer than the chimpanzee.
Life expectancy at birth of Hazara is 32.7 years old. If they live to adulthood, they can live an average of 40 years longer, three times longer than adult chimpanzees. Some elders of the Hazard even lived in their 80s. Obviously, their long life span has little to do with the advancement of medicine and technology.
Hazara is not an example. In 2007, Michael Gurven of the University of California, Santa Barbara, and Hillard Kaplan of the University of New Mexico analyzed all five modern hunters with demographic data available for research. tribe. The data showed that infection accounted for 72% of all causes of death, and the mortality curve of these tribes showed a “J” shape—a child mortality rate of 30%, a low youth mortality rate, and an exponential increase after age 40. Next, Gervin and Kaplan compare these curves with those of wild and captive chimpanzees: chimpanzees entered the fast-rising old age at least 10 years earlier than humans from the hunting collection tribe. Gervin and Kaplan summarized in the paper, “Obviously, chimps age faster than humans and die sooner, even in protected captive environments.”
When did human life begin to prolong?
In order to obtain clues, Rachel Caspari, an anthropologist at the University of Central Michigan, and Sang-Hee Lee of the University of California, Riverside studied 768 ancient human remains. It belongs to four ancient human groups and spans several million years. By measuring the wear of teeth (which can be used to presume age due to the constant rate of wear caused by chewing), they estimated that in each ancient human population, young people around 15 years old and middle age around 30 years old (at that At that time, this proportion of the age is enough to become a grandparent.)
Their research shows that only in the latter part of the long prehistoric period did the 30-year-old become common. The Australopithecus that appeared in Africa 4.4 million years ago, most of them died before the age of 30. In addition, the ratio between the age of 30 and about 15 is only 0.12. In contrast, Homo sapiens who lived in Europe from 10,000 to 44 thousand years ago often lived to be over 30 years old, and the ratio of individuals around the age of 30 to about 15 years old reached 2.08.
However, it is quite difficult to calculate the average life span of early Homo sapiens populations: At that time, demographic data such as birth and death records did not exist. The earliest complete statistics that Finch and his colleague Eileen Crimmins could analyze were from Sweden in 1751. In the decades that followed, modern medicine and health systems began to emerge.
Research shows that the average life expectancy of Swedes in the mid-18th century is about 35 years. However, if you escape the threat of infectious diseases such as bacterial infections and smallpox, live through childhood and live to 20 years of age, you are expected to live for another 40 years.
These discoveries made Finch very puzzled. These 18th-century Swedes settled in large, densely populated villages, towns, and cities and faced health threats that were even greater than the small group of migratory chimpanzees. Why do these Swedes live longer? The answer seems to come from meat-rich recipes of early human ancestors, as well as genes that have evolved to protect them from all kinds of pathogenic substances.
Apart from sleeping, chimps spend most of their time collecting delicious figs and other fruits. In order to find these foods rich in fructose, they need to travel through large areas and rarely stay in one place for two consecutive days. They are good at hunting small mammals such as red colobus monkeys, but they do not actively search for these prey. They don’t eat much meat. The primatologists who studied wild chimpanzees in Tanzania calculated that meat accounts for less than 5% of chimpanzees’ one-year recipes. In a Ugandan study, animal fats accounted for only the total dry weight of chimpanzees. 2.5%.
According to Finch, the earliest recipes for human members are probably plant-based. But at some time between 2.5 million and 3.4 million years ago, our ancestors began to ingest new animal protein foods, which is very important. Several sites in Ethiopia show that people at that time had begun to use simple stone tools to slaughter large ungulates such as antelopes. They smashed bones to feed on fat-rich bone marrow; they peeled the meat off the bones and in the leg bones and Ribs left a cut mark. About 1.8 million years ago, humans began to actively hunt large beasts and brought the entire animal carcasses back to camp.
New foods rich in calories and protein are likely to promote the development of the human brain, but also increase the chance of infection by pathogens in food. Finch suspects that this risk has prompted our ancestors to develop adaptation mechanisms so that they can survive the invasion of pathogens and live longer.
As more and more meat is eaten, our ancestors are increasingly exposed to germs. Early humans consumed dead carcasses of dead animals and consumed raw meat and viscera, which increased their chances of catching infectious bacteria.
In addition, when people hunt fierce large animals, they are likely to be injured and fractured, and these wounds can cause life-threatening infections.
The cooked food that appeared about 1 million years ago also brought dangers. The smoke that comes from the burning of wood every day can inhale a lot of toxic substances and smoke particles. In addition, meat is more delicious and easier to digest after being grilled, but at the same time it also produces chemicals known as “advanced glycation end products”, which can lead to serious diseases such as diabetes.
Since then, approximately 115,000 years ago, our ancestors entered the age of agriculture and animal husbandry. This has led to new dangers – daily exposure to animals such as cattle, sheep, pigs, chickens, etc., which has increased the rate at which humans infect bacteria or viruses from animals. risks of. In addition, when humans are permanently settled in a village, sewage generated by humans and livestock can contaminate local water sources and cause the proliferation of pathogenic bacteria.
Even so, facing so many health risks, Swedes in 1751 still live longer than chimpanzees.
In order to find the cause of human longevity, Finch began to study the academic literature about human and chimpanzee genomes. Previous studies published by others have shown that about 99% of the genomes of humans and chimpanzees are the same. But Hernán Dopazo, an evolutionary biologist at the Prince Felipe Research Center in Spain, and his colleagues noticed that in the 1% of genes unique to humans, there are a lot of genes that have undergone positive To select (refers to the influence of the external environment on the species, self-regulation and transformation of the genes, elimination of genes that are not adapted to the environment, production of genes that can effectively adapt to the environment), and host defense and immunity (especially a part called inflammatory response) ) plays an important role. Forward selection makes genes that are beneficial to the survival and reproduction of humans more and more common in the population and leave a unique “mark” in the DNA sequence.
The discovery of Dopaso gave Finch’s conjecture a new basis. He thought that perhaps it was natural choice to let humans have a better immune system to resist various health threats such as microorganisms brought about by the increase of meat, thus prolonging our life span.
In a war against the bacteria, viruses, and other microorganisms that are trying to invade us, the human host defense system has two “weapons”: innate immunity and adaptive immunity. Innate immunity is the first line of defense. It responds immediately after being attacked or injured, trying to eliminate the germs and repairing the damaged tissue. It is basically the same for any “invaders”. However, adaptive immunity is the opposite. It starts slowly and takes different coping styles for different pathogens. In this way, it can establish an immune memory that provides us with life-long protection against certain “invaders”.
The inflammatory response is part of the innate immune system. When tissues are attacked by microorganisms or toxins, or when they experience trauma, an inflammatory reaction occurs. Finch points out that doctors have long noticed the inflammatory response. About 2,000 years ago, Ancient Rome’s Aulus Cornelius Celsus (Encyclopedia of De Medicina) described the inflammation in the book. Important signs: fever, redness, swelling, and pain.
Finch explained that fever comes from the “energy factory” mitochondria in our cells, which dissipate energy as heat. This is a disinfection mechanism, he explained, “A lot of bacteria cannot reproduce or reproduce at temperatures above 40°C.” Swelling, on the other hand, is the release of material from damaged cells, allowing blood cells to leak fluid into the surrounding tissue to isolate the injured area from the surrounding healthy tissue.
Vinci began to detect human-specific genetic changes associated with host defenses. He soon noticed a change in the gene encoding apolipoprotein E (APOE). This gene plays an important role in the transport and metabolism of lipids, the development of the brain, and the functioning of the immune system. In the human body, there are mainly three types (alleles), of which the genes encoding APOE e4 and APOE e3 are the most common.
The DNA sequence of APOE e4 is close to that of the chimpanzee’s APOE, which means that APOE e4 is likely to appear 2 million years ago. When humans have just evolved, it is the first apolipoprotein to affect human life.
Compared to chimpanzee apoproteins, APOE e4 differs in several important amino acid positions, greatly increasing the rate of inflammation. APOE e4 also promotes the synthesis of proteins such as interleukin-6 (which causes elevated body temperature) and tumor necrosis factor alpha (which causes fever, prevents viral replication). Because of the powerful defense system, children of early humans can easily overcome difficulties when they eat or encounter harmful microbes.
“When humans climbed down from the trees and migrated to the prairies,” Finch noticed, “The chances of them being exposed to pathogens have increased dramatically. The prairie herbivores’ dung has not crossed the knees, and humans can only walk barefoot. ”
In addition, early humans with APOE e4 may well have acquired another crucial benefit: APOE e4 promotes intestinal absorption of lipids and efficient accumulation of body fat. When wild animals are scarce and hunting is difficult, early humans with APOE e4 can use stored fat to increase their chances of survival.
Even now, children with APOE e4 have a survival advantage over children without this protein. A study of young people in impoverished families in Brazilian shantytowns found that APOE e4 carriers have a lower probability of dying from diarrheal diseases caused by E. coli or Giardia than those without APOE e4. In addition, APOE e4 carriers also scored higher on cognitive tests, probably because they were more able to absorb cholesterol (an essential component of brain neuron development). “We think that the emergence of this protein will allow people to better adapt to the environment,” Finch commented.
The cost of longevity
Overall, APOE e4 seems to be an important part of solving the mystery of human longevity. Ironically, this gene that has allowed us to live longer has “betrayed” us in our later years. When more and more human ancestors can survive to middle and old age, its negative effects emerge. Now, in Lima, Finch and an international team of cardiologists, radiologists, biologists, and anthropologists are studying the cardiovascular tissue of ancient adult mummies in search of traces of these side effects. As ambassadors of the ancient era before the birth of modern medicine, these bodies became scientists’ important materials for studying aging.
In the imaging room in Lima, the screen shows a CT scan of a mummy. The owner of the mummy used in the study lived 1800 years ago. Gregory Thomas of the Long Beach Memorial Medical Center in the United States and Randall C. Thompson of the University of Missouri School of Medicine in Kansas City have found well-preserved aortas of soft tissue and tendons.
Next, they began to focus on scanning these arteries and found white thick plaques on the screen, which is a calcified plaque in the later stages of atherosclerosis (the main cause of myocardial infarction and stroke). Obviously, the owner of this mummy suffers from arterial calcification.
Medical imaging results show that arteries with clogged arteries were found in the mummies of Hatayy, an ancient Egyptian official. This suggests that cardiovascular disease is not a modern disease, but that humans pay for an excessively “vigilant” immune system. cost.
Cardiologists have long believed that atherosclerosis is a disease that originates from modern civilization. Some of the bad habits of contemporary people, such as smoking, lack of exercise, excessive calorie intake, and weight gain, increase the risk of arteriosclerosis. In addition, several recent studies have pointed out that the incidence of atherosclerosis has increased significantly in developing countries that are gradually becoming richer and lifestyles are becoming increasingly western. However, in 2010, Thomas and his colleagues decided to verify the hypothesis that “atherosclerosis is a modern, wealthy disease” by examining the arteries of ancient human mummies with CT scans.
In Egypt, Thomas’s research team examined 52 mummies from 2,500 to 3,500 years ago. Muhammad Al-Tohamy Soliman, a biological anthropologist at the National Research Center of Egypt, deduced the age of death of each individual based on tooth and skeleton development. The medical team conducted telephone discussions on Skype every week by carefully observing the results of the scan. Eventually, cardiovascular tissues were found in about 85% of mummies.
To their surprise, 45% of them are definitely or very likely to have atherosclerosis – it is clear that this ancient group was once threatened by this disease. “We were also shocked that so many young Egyptians also suffered from atherosclerosis,” said James Sutherland, a radiologist and research team member of the South Coast Radiologic Medical Group in the United States. James Sutherland said, “The average age of their death is about 40 years old.”
In the spring of 2011, after the papers of Thomas and colleagues were published in the Journal of the American College of Cardiology, Finch immediately contacted them and proposed a new one for the high incidence of atherosclerosis. Explanation. Vinci noticed that the living environment of the ancient Egyptians was full of plagues and various infections. Previous studies have shown that a large number of ancient Egyptians were exposed to a variety of infectious diseases, including malaria, tuberculosis and schistosomiasis, a disease caused by microscopic parasites in contaminated water. Among these individuals, APOE e4 carriers, because of the stronger immune system, are more likely to survive infections during childhood.
But in the next few decades, they will continue to suffer from chronic, severe inflammation caused by bacteria – researchers believe that this will lead them to fatal diseases of the elderly, including atherosclerosis and Alzheimer’s disease. In fact, the sign of atherosclerosis, arterial plaque deposition, appears to have occurred during the healing of inflammation and wounds on the vessel wall. Finch said, “It may be a bit far-fetched to describe Alzheimer’s senile plaques as scars on the arteries, but the two components are indeed very similar.”
Thomas and colleagues invited Vinci to join their team. Thomas and Vinci intend to continue to collect data together to conduct cardiovascular examinations of ancient mummies of various civilizations. The ancient Egyptians in the first study probably came from the wealthy upper class because they had money to make them mummy after they died. Such people may be less exercised and often consume foods with higher calorie content. So the research team decided to extend the study to other different civilizations.
They analyzed the mummies of Puebloan, Utah, and Unangan, Alaska. In addition, they analyzed the scans of the mummies on the coast of Peru. These ancients lived in 1500 BC, when the Spaniards had not yet arrived.
The research team published the results of the study on the Lancet. Of the 137 mummies examined, 34% were positive or very likely to have atherosclerosis. Importantly, these scans show that the disease exists in 4 ancient populations, including the hunter-gatherer Aleutians, who mainly feed on aquatic products.
The results of these studies challenge the claim that atherosclerosis is a modern disease and provide another explanation – before modern civilization, severe chronic infections and inflammation have led to atherosclerosis. The inflammation part.
Vinci said that although APOE e4 has strengthened our inflammatory response and increased our chances of living in a sexually mature period, it also cost us an expensive price, but the time for paying the price was delayed. Myocardial infarction, stroke, Alzheimer’s disease, and other chronic diseases of the elderly. In fact, APOE e4 is likely to be an example of an “antagonistic pleiotropy”: this gene can bring benefits in the early stages of life, but in the late stage it will require the body to pay a price.
“I think these ideas are very interesting,” said Steven Austad, a biologist and gerontologist at the University of Texas Health Science Center in San Antonio, Texas. “The evidence supporting these ideas is also very interesting.”
Improve the immune system
The study also found another gene related to our life span. About 200,000 years ago, when Homo sapiens emerged in Africa, another important APOE emerged. The gene encoding APOE e3 is beneficial to 40 to 70-year-old middle-aged and elderly people and can slow down the aging process.
Today, about 60% to 90% of people own this gene. Finch points out that the APOE e3 carriers have less inflammatory response than their ancestors. In addition, they seem to be more adaptable to high-protein, high-fat diets. Overall, APOE e3 carriers have lower cholesterol levels and fewer geriatric diseases such as coronary heart disease, cognitive decline, and Alzheimer’s disease. In fact, individuals carrying APOE e3 have a life expectancy of 6 years longer than their ancestors carrying APOE e4. According to Finch, “APOE e3 may be another factor that promotes the evolution of longevity.”
However, the gene encoding APOE is not the only gene associated with the evolution of human lifespan. Ajit Varki, a professor of medicine at the University of California, San Diego, and colleagues are studying several other genes that also make it easier for us to survive and live longer. Varki’s research focuses on SIGLEC, a gene that plays a key role in host defense. These genes can synthesize a transmembrane protein (ie, the structure of this protein is inside and outside the cell membrane) and can act as a “sentinel.” Varki explained that their role is to “discriminate the enemy.” This is not easy. In order to fool these “sentinels”, infectious germs will evolve camouflage skills and carry some proteins that allow the “sentinel” to mistake the germs as “own”.
The new discovery allowed some scientists to stop and think hard. For a long time, public health systems have warned people that the lack of exercise and high calorie diets in the evening are the main causes of atherosclerosis, myocardial infarction and high incidence of stroke. But new research – especially research on ancient mummies – shows that the fact is not so simple. Human genes and excessively alert immune systems may also be the cause of these diseases. “In other words, human control of atherosclerosis may be worse than expected,” said cardiologist Thompson. “We need to adjust our thinking. Perhaps the researchers should focus on those Unknown causes of illness.”
These new discoveries have also led to the ultimate question of human life — whether humans can or should evolve to live longer and longer? Some scientists predict that infants born after the year 2000 will live to 100 years in countries where life expectancy is high in itself (for example, the United States, Canada, the United Kingdom, and Japan). But Vinci privately expressed suspicion. He said that the current tendency of human obesity, and the environmental deterioration caused by climate change, may have a serious negative impact on human life, preventing the evolution of human longevity genes.
“I think we should be cautious about this,” said Finch. “I think time will prove everything.”