Aging is an irreversible natural physiological process with largely unknown causes. These changes affect each organ and each person differently. That’s according to two new studies, which provide important insight into the aging process. This research is particularly relevant given the World Health Organization (WHO) estimates that 21% of the world’s population will be over the age of 60 by the mid-2050s. The two investigations — one by a Dutch group and another by a Spanish team — indicate that the signs of aging begin earlier in women, but evolve more slowly than in men. The research also finds a person’s organs do not age at the same rate.
“Little is known about the specific changes that occur with aging in humans,” said Michel Ben Ezra, a researcher at the University of Copenhagen, who is the author of the Danish study.
Pablo Burraco, the author of the Spanish study, which also involved the University of Glasgow, agrees. “They say that if someone thinks they understand aging, it’s because they don’t know,” said Burraco, who is a scientist at the Doñana Biological Station of Spain’s National Research Council (EBD-CSIC),
Both scientists are trying to unravel the mechanisms of the aging process.
Research from the Center for Healthy Aging at the University of Copenhagen, published in Biorxiv and awaiting peer review, suggests that women show the first signs of aging from the age of 19, but that the process is more gradual than in men. In men, the first signs appear later, around the age of 40, but accelerate after that point.
To reach this conclusion, the researchers analyzed markers of cellular senescence in 33 million biopsy reports from 4.9 million people of all ages between 1970 and 2018. Despite the large sample size, the data set is one of the limitations of the study. All the reports are from individuals who underwent an examination for some pathology. “The biopsies were only taken when the participants sought medical attention. Male aging may therefore appear to begin later, as men tend to seek medical help when their symptoms are more advanced than their female counterparts,” Morten Scheibye-Knudsen, the co-author of the study, told New Scientist.
Manuel Tena-Sempere, professor of physiology at the University of Córdoba in Spain, explains that menopause is likely to be the most differential factor between how men and women age. “In the case of women, there is a drastic cessation of the secretion of ovarian hormones, and this has an important repercussion in the short, medium and long term that can condition female aging,” said Tena-Sempere. “In the case of men, if there is a decrease in androgen levels, it is gradual and its impact and consequences are very different.”
The Danish study also points out that not all tissues age in the same way, a finding confirmed by the study carried out by Spanish researchers in a paper published in Proceedings of the Royal Society B. This research focused on telomeres (chromosome ends), which shorten with age.
“Telomeres,” explained Burraco, “are not coders, but they are very important when cells divide. They shorten throughout life, but also as a response to stress, so they are not markers of chronological age but of biological age.”
The study was carried out in five different tissues of the frog species Xenopus laevis. This species was chosen since its metamorphosis — from embryo to larva and adult — allows scientists to observe very rapid changes in a short period of time. “We can see how these developmental changes affect different organs, how the animals that grow faster have shorter telomeres,” said Burraco.
“The changes in the different organs respond to very different dynamics. For example, in the liver, which grows a lot throughout life, we see a shortening [of telomeres] over time,” he added. “The expected pattern is for aging to be more or less gradual. But the heart remains very stable from the beginning of life. It seems that there are mechanisms that protect telomeres from shortening. In the case of the intestine, after metamorphosis [the larva is vegetarian and the adult is carnivorous] we observe longer telomeres that we attribute to the existence of a large number of stem cells.”
Telomere shortening occurs during cell division. “Every time they divide, they are not able to replicate the original sequences and they are shortened,” explained Burraco. It is a similar to what happens when a copy is made of a copy. In the process of copying, data is lost. “The protein that is responsible for replicating telomeres, telomerase, is not able to fully complete the process.”
Another factor is the amount of stress an organ is under during its development. “For example,” explained Burraco, “free radicals that are oxidizing hit DNA and cause it to break apart.”
Identifying these processes is the first step to finding ways to delay them. In the case of the intestine, where longer telomeres were seen after metamorphosis (like in the liver), researchers found that stem cells moved to the organ and helped “remodel it,” so that it would be better adapted to a carnivore’s diet. “It is a pattern of organ rejuvenation, meaning it’s one line of investigation to explore,” said Burraco.
Gene editing has also opened the door for direct action on telomeres. But the Spanish scientist is more cautious about this option. “I think it would be possible, but the problem is finding a balance because it could lengthen life, but also cause many problems,” he said. “You have to understand how far you can go. We don’t want to be triggering uncontrolled cell reproduction, leading to cancer, for example.”
Burraco is seeking to continue his research into aging, focusing on how the increase in telomerase activity and the reduction of oxidative stress affect the process.
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