According to recent studies, different parts of our body age at different rates, and the age of some organs can far exceed that of their owners. But will a deeper understanding of this phenomenon help us learn to live longer?
The situation was desperate. A 19-year-old Turkish girl with liver disease urgently needed a transplant. While waiting for her turn, she developed hepatic encephalopathy, a buildup of toxins in the blood due to liver dysfunction, which had already begun to affect her brain function. Time was running out, and the only option for transplantation was an organ that had already been rejected by several hospitals. This liver was considered unsuitable for transplant – not only because it had a cyst formed as a result of a parasitic infection, but also because its previous owner was a recently deceased 93-year-old woman. By all transplant standards, the organ was too old, especially considering that the recipient was significantly younger. But there was no other choice, and the doctors decided to go ahead with the transplant. Surprisingly, the operation, performed in 2008 at the Liver Transplant Institute in the Turkish city of Malatya, was a complete success: the young patient survived and six years later gave birth to a healthy child. When her daughter turned one, the mother was 26, and her liver was celebrating its 100th birthday. Few of us will understand what it’s like to have a liver the age of your great-grandmother.
Surprisingly, however, there is something else: how different our organs and tissues age at different rates. This difference in aging can tell us much more about the state of our body than our chronological age, which turns out to be less important. In fact, scientists are much more interested in the degree of discrepancy between your chronological age and your biological age, which indicates how old your body and its individual organs are.
The number of recipients with transplanted livers over 100 years old is steadily increasing. We explain quickly, simply, and clearly what happened, why it matters, and what will happen next. The number of episodes should remain the same. End of story: Podcast Advertising. Of course, these two factors can be related, but even intuitively it is clear that they are not always related. We all know very well that if we constantly lack sleep and eat whatever we can, we will age prematurely. Aging is often thought of as a gradual process, something that happens to the body as a whole, although at different rates for different people. However, this approach does not provide a complete picture. Research shows that a complex combination of factors (genetics, lifestyle, environmental conditions) affects different organs differently. So we can look quite youthful at the age of 38, while our kidneys will be in the condition as if they were transplanted from a 61-year-old person, as one of the studies showed. And it could be like this: a person has many wrinkles on his face, his head is bald like that of an 80-year-old man, but his heart is no older than 40. Stanford University geneticist Michael Snyder compares it to a car. “Over time, the car as a whole starts to malfunction, but its individual parts and components wear out faster than others,” he says. “If the engine starts to fail, you can fix it. If there are defects in the body, you can take the car to the body shop, where it will be repainted and patched up. And so on.”
So even if we know our overall biological age, in order to live longer and healthier, we must first realize that different organs age at different rates. However, accurately determining the biological age of an individual organ is a challenging task. Although many websites offer to estimate the age of your heart or lungs using a “calculator,” in reality, a more or less accurate picture requires a detailed study of the specific organ’s functions, tissue structures, cells, and genetic health. Meanwhile, the data collected by transplantation specialists gives us a unique opportunity to find out which organs specifically cope better with aging. Researchers who compare the age of donors with how long recipients live after transplantation have found that transplants of older organs are generally less successful. However, much depends on the specific organ being transplanted. While the success of heart and pancreas transplants decreases after the age of 40 (donor age), no difference is observed in lung transplants until the age of 65. The most resistant organ to aging is the cornea – the age of the donor does not seem to matter.
Red blood cells usually live only a few months before they are replaced by new ones. However, other types of cells, such as nerve cells, usually live with us from birth to death. Researchers at the University of Liverpool believe that the key factor in how an organ copes with age is its relative complexity, along with the degree to which it depends on the health of its blood vessels. “It is logical to assume that age-related changes in the vessels and microvessels of various organs should be a serious factor exacerbating age-related disorders,” the scientists write.
The data collected by transplantologists also raises questions about the existence of a life limit for a particular organ. For example, the liver is known for its regenerative potential, and in patients who have up to two-thirds of the organ removed, the liver regenerates almost completely to its previous size within a year. Some researchers suggest more active use of ninety-year-olds as potential liver donors, citing several successful transplants in recent years. Other scientists are following a small number of patients whose livers have reached 100 years of age after transplantation, several decades earlier than their new owners. “Some organs may be more sensitive to different aspects of our lifestyle. A very good example is the lungs and pollution,” says Richard Siaw, Director of Aging Research at the Royal College London. “The lungs age faster in people who live in big cities or places where the air is heavily polluted.” According to Siau, there are many factors that affect how we age. “What and how we eat, how and when we sleep – all of these affect our organs in different ways that we don’t fully understand,” he says.
At the microscopic level, the concept of organ aging becomes even more fuzzy. Individual cells cause most of our organs to wear out and require replacement on a regular enough basis. This means that many tissues completely regenerate over time, but the rate of regeneration varies greatly from organ to organ. A single red blood cell circulates in our veins and arteries for an average of four months, while it must be replaced in the intestines within a few days. On the other hand, most brain cells, or neurons, are not replaced with age, and they tend to age the same as the rest of the body. But in 2019, a team of scientists led by Martin Hetzer of the Salk Institute for Biological Studies (USA) discovered that neurons are not the only cells in mammals that can boast a long lifespan. It turns out that in mice, liver and pancreatic cells of the same age as the animal itself coexist with younger cells – this is called “genetic mosaicism. Since long-lived cells are more susceptible to age-related changes and wear and tear than those that exist for only a few days, the fact that such cells exist not only in the brain may give researchers clues to unraveling the mechanisms of organ aging.
No matter how resilient our organs are in the face of aging, they all gradually slow down over time. However, recent studies have shown that we can predict which organs will fail first.
People age at different rates, so the number of years we have lived does not tell us much until we understand our biological age. In 2020, Snyder and his colleagues at Stanford University identified at least 87 molecules and microbes in the body that could be used as biomarkers of aging. After studying how these markers changed in a group of volunteers during several quarterly checkups over two years, scientists concluded that people seem to age according to certain biological mechanisms. They also understood that by grouping biomarkers based on which organ or system they are most closely associated with, people could be categorized into different “stereotypes,” or types of aging. Scientists have found evidence for the existence of four different types of aging based on the body’s major aging pathways (kidney, liver, metabolism, and immunity), but they believe there are others, such as cardiovascular aging. Remarkably, researchers have been able to identify people’s “stereotypes” (which Snyder says can be reduced to a combination of genetics and environment) long before they age. If the Stanford scientists are right, young people will one day be able to get information from specialists about which specific aspects of their health they should pay special attention to as they age. “For example, if you are aging in terms of cardiovascular health, then you should monitor your levels of bad cholesterol, get your heart checked regularly, and exercise,” says Snyder. “If you are aging metabolically, watch your diet. Those who are aging in terms of liver health should try to consume less alcohol. And so on.” Critics point out that we do not yet know whether the physiological changes found in a relatively short-term study by Stanford scientists will lead to negative health consequences in the long term. But Snyder is certain that we are on the cusp of an era of a more personalized approach to preventing aging. “You can’t cut everyone with a broad brush here,” he says. “Exercise and proper nutrition in general can help, but if your heart or kidneys are worn out, you probably need a more targeted strategy.”
With the help of computer technology, scientists are able to more accurately assess the degree of biological aging. One of the methods is to study semi-permanent changes in our DNA (DNA methylation), which is thought to be influenced by our lifestyle and environment. The level of methylation changes with age – as our epigenetic processes change. This has allowed scientists to develop “epigenetic clocks,” clocks of methylation that can determine the biological age of tissues, cells, or organs. These clocks also make it possible to compare the biological age of different tissues. For example, there is evidence that female breast tissue ages faster than other tissues in the body, raising the question of whether epigenetic clocks can be used to predict the development of breast cancer.
Although regular physical activity and proper nutrition can help maintain good health into old age, a more targeted approach is also beneficial. However, some scientists point out that even if everything works exactly like this, it is far from certain that slowing down these clocks will also slow down the aging process. However we look at aging, the ultimate goal for many researchers is not just to slow the clock, but to turn back time. It appears that this is already possible at the cellular level. In March 2020, researchers at the Stanford School of Medicine reported that they were able to rejuvenate cells taken from elderly people by inducing them to produce proteins that reverse cell development to an embryonic state. After a few days, the cells looked like they were years younger. Doing the same thing with an entire organ seems much more difficult, but this study is just the first step toward new methods that will help reverse the biological clocks of cells and tissues.
Today, however, many scientists are focusing more on extending the healthy life span of older people. A recent review by Linda Partridge and colleagues at University College London focuses on drugs such as rapamycin, metformin and lithium that may help slow the onset of age-related diseases and problems. It should be noted, however, that none of these agents is capable of reversing all the numerous symptoms of aging. Other researchers agree that anti-aging products may only be able to affect the condition of specific tissues. That’s why it’s so important to understand how aging affects different organs. But no matter how differently the organs age, it makes sense to monitor them as a whole. Richard Siaw emphasizes that they are interconnected and interdependent, and that rapid aging of one inevitably affects the others. “If your joints are inflamed, it affects both your brain and your heart,” he says. “Each organ has its own aging dynamics, but they are all interconnected.”
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