If you have ever felt like everything in your body is breaking down at once, it might not just be your imagination as a new study has found that many of our molecules and micro-organisms increase or decrease substantially during our forties and sixties. Researchers assessed thousands of molecules in people aged from 25 to 75, as well as their microbiomes – the bacteria, viruses and fungi that live inside us and on our skin – and found that most do not shift in a gradual, chronological fashion. The research, published in the journal <i>Nature Aging,</i> found we undergo two periods of rapid change during our lifespan, beginning at around 44 and 60. “We’re not just changing gradually over time – there are some really dramatic changes,” said Michael Snyder, PhD, chairman of genetics at Stanford University in the US, and the study’s senior author. “It turns out the mid-forties is a time of dramatic change, as is the early sixties. And that’s true no matter what class of molecules you look at.” These big changes affect our health. The number of molecules related to <a href="https://www.thenationalnews.com/health/2023/08/27/low-birth-weight-gives-clue-to-later-heart-disease/" target="_blank">cardiovascular disease</a> showed significant changes at both time points and those related to <a href="https://www.thenationalnews.com/health/2024/06/11/scientists-work-on-the-immune-system-in-space-provides-clues-on-how-to-stop-aging/" target="_blank">immune</a> function changed in people in their early sixties. The new study analysed participants who donated blood and other biological samples every few months over the span of several years. The scientists tracked molecules in these samples, including RNA, proteins and metabolites, as well as shifts in the participants’ microbiomes. The researchers traced age-related changes in more than 135,000 different molecules and microbes, for a total of nearly 250 billion data points. They found that thousands of molecules and microbes undergo shifts in their abundance, either increasing or decreasing. About 81 per cent of all the molecules they studied showing non-linear fluctuations in number, meaning that they changed more at certain ages than other times. When they looked for clusters of molecules with the largest changes in amount, they found these transformations occurred the most in two time periods: when people were in their mid-forties, and when they were in their early sixties. Scientists were surprised by the large cluster of changes in the mid-forties. At first, they assumed that menopause or perimenopause was driving large changes in the women in their study, skewing the whole group. But when they broke out the study group by sex, they found the shift was happening in men in their mid-forties, too. “This suggests that while menopause or perimenopause may contribute to the changes observed in women in their mid-forties, there are likely other, more significant factors influencing these changes in both men and women,” Xiaotao Shen, PhD, the first author of the study, said. “Identifying and studying these factors should be a priority for future research.” For people in their forties, significant changes were seen in the number of molecules related to alcohol, <a href="https://www.thenationalnews.com/health/2023/03/14/blood-caffeine-levels-clue-to-staying-slim-and-less-diabetes-risk/" target="_blank">caffeine</a> and lipid metabolism, cardiovascular disease, and skin and muscle. In those in their sixties, changes were related to carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular disease, and skin and muscle. Researchers believe some of these changes could be tied to lifestyle or behavioural factors that cluster at these age groups, rather than being driven by biological factors, Dr Snyder said. For example, dysfunction in alcohol metabolism could result from an increase in alcohol consumption in people’s mid-forties, often a stressful period of life. The team plans further work to explore the drivers of these clusters of change. The existence of these clusters points to the need for people to pay attention to their health, especially in their forties and sixties, the researchers said. This could include increasing exercise to protect your heart and maintain muscle mass at both ages, or decreasing alcohol consumption in your forties as your ability to metabolise alcohol slows. “I’m a big believer that we should try to adjust our lifestyles while we’re still healthy,” Dr Snyder said.