The progress of a human being through life might be thought of as a mostly gradual succession of changes from the ovum to the grave.
But if you wake up one morning, look in the mirror, and wonder when you suddenly grew so much older, you may not be imagining things. According to new research into the molecular changes associated with aging, humans experience two drastic lurches forward, one at the average age of 44 and the other at the average age of 60.
“We’re not just changing gradually over time; there are some really dramatic changes,” says geneticist Michael Snyder of Stanford University, senior author of the study.
“It turns out the mid-40s is a time of dramatic change, as is the early 60s. And that’s true no matter what class of molecules you look at.”
Aging is complex, and associated with growing risks of diseases of all kinds. Snyder and his colleagues have been investigating the biology of aging to better understand what changes occur and how, in order to better mitigate and treat these ailments. To this end, they have been tracking a group of 108 adults, who have been donating biological samples every few months over several years.
They noticed that in some conditions, such as Alzheimer’s and cardiovascular disease, risk doesn’t rise gradually with time, it escalates sharply after a certain age. So they wanted to take a closer look at the biomarkers of aging to see if they could identify related changes.
Using the samples from their cohort, the researchers have been tracking different kinds of biomolecules. The different molecules studied include RNA, proteins, lipids, and gut, skin, nasal, and oral microbiome taxa, for a total of 135,239 biological features.
Each participant submitted an average of 47 samples over 626 days, with the longest-serving participant submitting 367 samples. This wealth of data resulted in more than 246 billion data points, which the researchers then processed, looking for patterns in the changes.
Several previous studies have found non-linear changes in molecular abundances that can be linked to aging in rats and humans. Studies of fruit flies, mice, and zebrafish have also pointed to a stepwise aging process in those species.
Snyder and his colleagues noticed that there’s a very clear change in the abundances of many different kinds of molecules in the human body at two distinct stages. Around 81 percent of all the molecules in their study showed changes during one or both of these stages. Changes peaked in the mid-40s, and again in the early 60s, with slightly different profiles.
The mid-40s peak showed changes in molecules related to the metabolism of lipids, caffeine, and alcohol, as well as cardiovascular disease, and dysfunctions in skin and muscle. The early 60s peak was associated with carbohydrate and caffeine metabolism, cardiovascular disease, skin and muscle, immune regulation, and kidney function.
The first peak, the mid-40s, is typically when women start undergoing menopause or perimenopause, but the researchers ruled this out as a main factor: men, too, also underwent significant molecular changes at the same age.
“This suggests that while menopause or perimenopause may contribute to the changes observed in women in their mid-40s, there are likely other, more significant factors influencing these changes in both men and women,” explains metabolomicist and first author Xiaotao Shen, formerly of Stanford, now at Nanyang Technological University Singapore.
“Identifying and studying these factors should be a priority for future research.”
The researchers note that their sample size is pretty small, and they tested limited biological samples, from people between the ages of 25 and 70. Future research could help delve further into this phenomenon, studying it in more granular detail, across a wider range of subjects, to better understand how the human body changes over time.
The research has been published in Nature Aging.
