Harnessing the power of a metabolite produced in the kidneys and absorbed from certain foods can mimic the health benefits delivered by exercise, regulating inflammation and promoting an array of anti-aging processes without any physical activity.
A team of scientists led by the Institute of Zoology of the Chinese Academy of Sciences has uncovered how the naturally produced metabolite betaine acts as a "molecular proxy" for actual exercise. So when administered at a level seen in people who are highly active, it can stall – and potentially even reverse – aging in kidney, vascular and immune cells.
While we're yet to find a silver bullet that delivers the widespread health benefits of exercise without the physical investment, it hasn't stopped researchers from trying. There have been some promising developments in recent years, and GLP-1 receptor agonist drugs have shown that we're rapidly discovering new ways to manipulate natural processes in our favor.
In a study that spanned six years, the researchers mapped intricate molecular activity of 13 young, healthy males who undertook both intensive, high-effort workouts and more enduring exercise such as long-distance running, to see what these two modes of physical activity could be triggering. What they found was that, surprisingly, the kidneys appeared to play a key role in shielding cells from natural aging processes.
And yes, it's worth pointing out that the study cohort was restricted to just males, which the researchers acknowledge is the key limitation of their findings.
Nonetheless, the team discovered that, in endurance trainers, certain biomarkers of inflammation and cellular aging were much lower than control samples. (Meanwhile intensive, short bursts of exercise, on the other hand, triggered more cellular distress including cortisol spikes and oxidative stress.)
In endurance trainers, the researchers noticed how sustained exercise dialed down the transcription factor ETS proto-oncogene 1 (ETS1), which is a DNA-binding protein that plays a big role in regulating cellular processes including immunity and ribosomal biogenesis – which is closely tied to how well cells age. And there was also a boost in betaine synthesis in the kidneys, which was not a target of the study. They noticed that betaine levels rose significantly in the bloodstream of older individuals after regular exercise, which through further analysis appeared closely tied to improvements in muscle strength, metabolism and mitochondrial health. So this led them to ask: What if betaine isn't a passive biomarker of exercise but plays an important role in the health benefits of working out?
The team homed in on this metabolite, administering oral doses to aged mice – an animal model that could best mirror humans – and then assessed changes in muscle strength, endurance, mitochondrial function, inflammatory markers and gene expression. They found that these older animals showed significant improvements in those same health markers that otherwise resulted from endurance training. They also had reduced inflammation and enhanced tissue regeneration.
Essentially, betaine mimicked the systemic effects of exercise, even though the mice weren’t physically active.
"This resolves the exercise paradox," said Professor LIU Guanghui, a co-corresponding author of this study. "Acute exercise initially triggers a survival-oriented inflammatory response and oxidative stress via the IL-6/cortisol pathway. However, long-term exercise suppresses inflammation and oxidative damage through kidney-generated betaine."
Betaine is a naturally occurring compound found in foods like beets, spinach and whole grains, and plays an important role in cell protection, detoxification, muscle performance and mitochondrial function – all crucial in longevity. Boosted levels, in the older mice, enhanced these anti-aging processes much like they did in the endurance trainers.
While broader, more inclusive studies are needed, these findings hold great potential for the safe supplementation of betaine for people who are unable to reap the benefits through physical activity.
"Unlike exercise-induced signaling molecules from muscle and other organs,betaine – a kidney-derived metabolite identified in our study – showed anti-inflammatory and geroprotective potential," the researchers noted. "Our study delineated the molecular blueprint through which exercise reshapes human physiology, providing mechanistic insights into its health benefits. The identified exercise-induced factors, including betaine, offer potential for developing 'exercise in a pill' to promote healthy aging."
The study was published in the journal Cell.
Source: Chinese Academy of Sciences