Betaine May Explain How Exercise Slows Biological Ageing

Scientists know that exercise benefits health, yet the fundamental molecular reasons for those benefits are still being worked out. A small new study conducted over a longer period may have provided an important clue, identifying the metabolite betaine as a major contributor to exercise’s positive effects.

Betaine is a small molecule present in foods including sugar beet and spinach. Although earlier research has associated it with better health, it had not previously been linked with exercise.

Betaine and the benefits of exercise

A research team led by scientists at Xuanwu Hospital, Capital Medical University, China, found that sustained exercise raises betaine levels in the body through the kidneys.

Furthermore, betaine can reproduce certain advantages of exercise, particularly the slowing of biological ageing, also known as geroprotection. This molecule may therefore have the potential to help people remain healthier for longer.

"This study gives us a fresh way to turn how our body works into something we can target with chemicals," says biophysicist Liu Guang-Hui, from the Chinese Academy of Sciences.

"It opens the door to geroprotective treatments that can tweak how multiple organs work together."

How regular running changes the body

The researchers examined exercise’s effects in 13 healthy male volunteers. They used multi-omics, an approach that tracks changes at the most fundamental bodily levels, including genes, proteins, the immune system and small molecules such as betaine.

Following one 5-kilometre run, the team observed an intense but brief stress response. By contrast, a month of routine running produced more lasting improvements in several respects: less cellular ageing and damage, alongside a healthier gut microbiome and immune system.

The kidneys of these volunteers also produced considerably more betaine, another central finding. Experiments in mice then showed that betaine inhibits an enzyme known as TBK1, which has previously been associated with inflammation and ageing in the body.

Put simply, elevated betaine is not merely an outcome of maintaining consistent, long-term exercise. These chemical increases actively help produce some of exercise’s benefits, particularly its anti-ageing effects.

"Our study delineated the molecular blueprint through which exercise reshapes human physiology, providing mechanistic insights into its health benefits," the researchers write in their published paper.

"The identified exercise-induced factors, including betaine, offer potential for developing 'exercise in a pill' to promote healthy aging."

Potential for geroprotective treatments

The researchers are not claiming that people will soon be able to take tablets in place of going to the gym. Exercise has many benefits that this research did not address, among them greater muscle strength and improved mental health.

Nevertheless, betaine and the other biological changes identified in the study could help guide the development of medicines designed to lower the risk of age-related disease and maintain the body in better condition. Such treatments could be relevant both to older people and to those unable to exercise for a range of reasons.

Substantially more research is required, involving far larger groups of people and much longer exercise periods. Even so, the discovery that betaine plays a vital role offers a promising avenue for researchers to investigate.

"This redefines 'exercise as medicine'," Guang-Hui says.

The research was published in Cell.