For many people, reaching their mid-40s may bring unpleasant signs the body isn’t working as well as it once did. Injuries seem to happen more frequently. Muscles may feel weaker.

A new study, published Wednesday in Nature Aging, shows what may be causing the physical decline. Researchers have found that molecules and microorganisms both inside and outside our bodies are going through dramatic changes, first at about age 44 and then again when we hit 60. Those alterations may be causing significant differences in cardiovascular health and immune function.

The findings come from Stanford scientists who analyzed blood and other biological samples of 108 volunteers ages 25 to 75, who continued to donate samples for several years. 

“While it’s obvious that you’re aging throughout your entire life, there are two big periods where things really shift,” said the study’s senior author, Michael Snyder, a professor of genetics and director of the Center for Genomics and Personalized Medicine at Stanford Medicine. For example, “there’s a big shift in the metabolism of lipids when people are in their 40s and in the metabolism of carbohydrates when people are in their 60s.”

Lipids are fatty substances, including LDL, HDL and triglycerides, that perform a host of functions in the body, but they can be harmful if they build up in the blood.

The scientists tracked many kinds of molecules in the samples, including RNA and proteins, as well as the participants’ microbiomes.

The metabolic changes the researchers discovered indicate not that people in their 40s are burning calories more slowly but rather that the body is breaking food down differently. The scientists aren’t sure exactly what impact those changes have on health.

Previous research showed that resting energy use, or metabolic rate, didn’t change from ages 20 to 60. The new study’s findings don’t contradict that.

The changes in metabolism affect how the body reacts to alcohol or caffeine, although the health consequences aren’t yet clear. In the case of caffeine, it may result in higher sensitivity. 

It’s also not known yet whether the shifts could be linked to lifestyle or behavioral factors. For example, the changes in alcohol metabolism might be because people are drinking more in their mid-40s, Snyder said.

For now, Snyder suggests people in their 40s keep a close eye on their lipids, especially LDL cholesterol.

“If they start going up, people might want to think about taking statins if that’s what their doctor recommends,” he said. Moreover, “knowing there’s a shift in the molecules that affect muscles and skin, you might want to warm up more before exercising so you don’t hurt yourself.”

Until we know better what those changes mean, the best way to deal with them would be to eat healthy foods and to exercise regularly, Snyder said.

Dr. Josef Coresh, founding director of the Optimal Aging Institute at the NYU Grossman School of Medicine, compared the new findings to the invention of the microscope.

“The beauty of this type of paper is the level of detail we can see in molecular changes,” said Coresh, a professor of medicine at the school. “But it will take time to sort out what individual changes mean and how we can tailor medications to those changes. We do know that the origins of many diseases happen in midlife when people are in their 40s, though the disease may occur decades later.”

The new study “is an important step forward,” said Dr. Lori Zeltser, a professor of pathology and cell biology at the Columbia University Vagelos College of Physicians and Surgeons. While we don’t know what the consequences of those metabolic changes are yet, “right now, we have to acknowledge that we metabolize food differently in our 40s, and that is something really new.”

The shifts the researchers found might help explain numerous age-related health changes, such as muscle loss, because “your body is breaking down food differently,” Zeltser said.

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