Scientists have found that the human body undergoes two dramatic bouts of rapid physical transformation on a molecular level, with the shifts in abundance of more than 135 000 types of molecules and microbes relating to age not occurring gradually, but clustered around 44 and 60.
For many, middle age is associated with midlife crises and internal tumult, but according to the recent research, it is also when the human body undergoes these changes, reports The Washington Post.
In the study, scientists at Stanford University tracked age-related changes in more than 135 000 types of molecules and microbes, sampled from more than 100 adults. They discovered that shifts in their abundance, either increasing or decreasing in number, did not occur gradually over time, but clustered around two ages.
“Obviously you change throughout your entire life. But there are two major periods when there are lots of changes. One is when people hit their mid-40s, and the second in their 60s,” said Michael Snyder, a geneticist at Stanford University who co-wrote the study. On average, the changes clustered around the ages of 44 and 60.
Markers of age increase sporadically
The peer-reviewed study, published in the journal Nature Ageing, offers further evidence that the markers of age do not increase at a steady pace, but more sporadically. The focus on molecular change could also offer future researchers a clue into the drivers of age-related diseases, although it is too early to say precisely how molecular change is related to ageing.
“When people become old, the molecules in their bodies change,” said Xiaotao Shen, a computational biologist at Singapore’s Nanyang Technological University who co-wrote the study while at Stanford. “What we don’t know is what drives this change.”
The findings also underscore the importance of a person’s lifestyle once they enter their 40s, the scientists said – advising people to improve their diet and exercise at this age, when the body begins to change.
Swabs and observation
Every three to six months, the scientists took oral, skin and nasal swabs, as well as blood and stool samples, from 108 adults. On average, participants were observed for a relatively short period, with a median of less than two years. The participants were aged 25 to 75, healthy and from diverse ethnic backgrounds.
The scientists then analysed 135 239 different molecules and microbes, including RNA, proteins and metabolites, from the samples, forming 246bn data points from across the time span. A statistical analysis revealed that most of observed molecules – 81% – did not fluctuate in number continuously, but changed around two ages significantly.
“In the mid-40s and 60s, that seems to be where most changes were occurring,” said Snyder.
As part of the study, the scientists observed changes in molecules and microbes including proteins, metabolites and lipids, which are related to cardiovascular function, the immune system, metabolism, and skin and muscle.
Differences between the two ages
Changes in molecules related to cardiovascular disease, the metabolism of caffeine, and skin and muscle were observed at both ages, the scientists found, but there were also some differences between the two ages.
For participants in their mid-40s, for example, marked changes included those observed in molecules related to the metabolism of alcohol and lipids (or fats). For those in their 60s, notable fluctuations were observed in molecules related to immune regulation, kidney function and the metabolism of carbohydrates.
Snyder said the molecular changes observed in the 60s was not surprising. “A lot of age-related diseases kick in then: cardiovascular disease, cancer,” he pointed out.
But the changes observed in the 40s, Snyder said, were initially surprising. After breaking down the study’s results by sex, the authors found that the shift was also observed in men in their mid-40s, discounting the possibility that the dramatic changes could be accounted for solely by the onset of menopause or peri-menopause in women.
“In hindsight, it makes intuitive sense,” Snyder said, referring to the molecular shifts observed in both sexes in the mid-40s. “People who do a lot of exercise realise when they hit their 40s that they’re not quite the same as they were in their 20s.”
The exact reason these molecular changes cluster at the mid-40s and 60s is unclear. But the study’s authors say their findings show that from their 40s, people stand to gain particular benefits from taking care of their health. This includes having regular medical check ups – at least twice a year when they’re in their 40s, Shen suggested, as well as making lifestyle adjustments.
“For example, if you know that your carbohydrate metabolism is going off, there’s something you can do about that: changing your diet,” said Snyder, who generally advises people in their midlife to exercise and eat a healthy diet.
“We found that the metabolism ability for alcohol and coffee decreases at around 40 and 60,” Shen said, suggesting that people at these ages would benefit from reducing their consumption of both.
Some people who could once drink multiple cups of coffee a day and had no trouble sleeping may suddenly find in their 40s that a single cup of coffee is enough to inhibit a good night’s sleep, he added.
Age-related diseases
David Clancy, a lecturer in biogerontology at England’s University of Lancaster who was not involved in the research, said that the study can help offer an insight into the causes of ageing by identifying which molecules are directly linked to age-related diseases. “Ultimately, of course, this might help identify therapeutic targets,” he said.
The molecules analysed in this study, Clancy said, are often linked to age-related diseases and characteristics such as thrombosis and cardiovascular disease, skin and muscle stability, immune senescence, kidney function and carbohydrate metabolism.
The authors cautioned that it was possible some of the observed molecular changes, like the ability to metabolise alcohol, could be related to behavioural changes that take place around the same age, as opposed to factors relating directly to age biology.
The researchers also noted that the length of the study was too short for tracking changes that unfold over decades. Longer-term research, they say, could offer better insight into how observed molecular changes align with longer-term changes in functional capacities, disease occurrences and mortality hazards. The number of participants was also relatively small.
Researchers hope to better understand the factors driving these molecular changes, Shen said. “If we can find the drivers of these changes, we may even be able to find ways to slow or even reverse the drivers of the ageing at these two time points.”
Study details
Nonlinear dynamics of multi-omics profiles during human ageing
Xiaotao Shen, Chuchu Wang, Xin Zhou, Wenyu Zhou, Daniel Hornburg, Si Wu &
Michael Snyder.
Published in Nature Ageing on 14 August 2024
Abstract
Ageing is a complex process associated with nearly all diseases. Understanding the molecular changes underlying aging and identifying therapeutic targets for aging-related diseases are crucial for increasing healthspan. Although many studies have explored linear changes during aging, the prevalence of aging-related diseases and mortality risk accelerates after specific time points, indicating the importance of studying nonlinear molecular changes. In this study, we performed comprehensive multi-omics profiling on a longitudinal human cohort of 108 participants, aged between 25 years and 75 years. The participants resided in California, United States, and were tracked for a median period of 1.7 years, with a maximum follow-up duration of 6.8 years. The analysis revealed consistent nonlinear patterns in molecular markers of aging, with substantial dysregulation occurring at two major periods occurring at approximately 44 years and 60 years of chronological age. Distinct molecules and functional pathways associated with these periods were also identified, such as immune regulation and carbohydrate metabolism that shifted during the 60-year transition and cardiovascular disease, lipid and alcohol metabolism changes at the 40-year transition. Overall, this research demonstrates that functions and risks of aging-related diseases change nonlinearly across the human lifespan and provides insights into the molecular and biological pathways involved in these changes.
Nature Ageing article – Nonlinear dynamics of multi-omics profiles during human ageing (Open access)
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