“When people become old, the molecules in your body 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.

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, participations 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 some 135,239 different molecules and microbes – including RNA, proteins and metabolites – from the samples, forming 246 billion data points from across the timespan. A statistical analysis revealed that the majority 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.

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 were 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 perimenopause 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 for why these molecular changes cluster at the mid-40s and 60s is unclear. But the study’s authors say their findings show that from your 40s, people stand to gain particular benefits from taking care of their health. This includes getting regular medical check-ups – at least twice a year once you hit your 40s, suggests Shen – 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 around 40 and 60 years old,” 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 have no trouble sleeping may suddenly find in their 40s that a single cup of coffee is enough to inhibit a good night’s sleep that night, he pointed out.

David Clancy, a lecturer in biogerontology at England’s University of Lancaster, who was not involved in the research, said the study could help offer an insight into the causes of ageing by identifying which molecules were directly linked to age-related diseases. “Ultimately, of course, this might help identify therapeutic targets,” Clancy said.

The molecules analysed in this study, Clancy pointed out, are often linked to age-related diseases and characteristics like 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 – such as 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. “We don’t always know what’s cause and effect,” Snyder said, pointing out the possibility that people are simply consuming more alcohol at those ages.

The authors also cautioned 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.”