Stronger biological rhythms throughout the day may sluggish aging and extend lifespan, according to a modern study led by Peking University in China. The research establishes a link between circadian rhythms – the body’s natural internal clock – and longevity, offering potential new avenues for therapies aimed at promoting healthy aging. Maintaining a regular sleep schedule, consistent meal times, and stable daily exposure to light and darkness are recommended to support these natural rhythms.
Circadian rhythms govern a wide range of biological processes that cycle on roughly a 24-hour period, including sleep-wake cycles, body temperature, blood pressure, and cortisol secretion. The study pinpointed the paraventricular nucleus (PVN) within the hypothalamus as the brain region responsible for regulating the amplitude of these rhythms – essentially, the difference between the highs and lows of these biological processes.
Researchers Recommend Regular Sleep and Meal Schedules and Limiting Evening Light Exposure
Previous research has indicated that the amplitude of circadian rhythms tends to decrease with age. In experiments conducted with mice, stimulating the PVN with a drug restored the amplitude of circadian rhythms, reduced multiple biomarkers of aging, and extended lifespan by 12%. The findings are published in the journal Cell, and could have implications for future anti-aging interventions.
“Currently, You’ll see no approved drugs to amplify circadian rhythms in the PVN,” said Dapeng Ju, co-author of the research from Chongqing Medical University. However, “our results establish the PVN as a promising therapeutic target that can be acted upon pharmacologically; in the future, therapies could be developed to reinforce circadian rhythms in this hypothalamic circuit.”
While the research was conducted on mice, the fundamental mechanisms regulating circadian rhythms are shared among mammals, suggesting the findings may be applicable to humans. Ju emphasized that individuals can capture steps to protect their circadian rhythms. “The circadian system performs best with regularity,” he stated. “Good sleep habits are important for maintaining circadian health, as are regular meal times and avoiding excessive light exposure at night.”
These recommendations are particularly important for individuals with metabolic disorders such as diabetes or obesity, as they are especially vulnerable to disruptions in circadian rhythms, the researchers noted.
The new research “shows for the first time that modulating the circadian rhythm has a rejuvenating potential,” said Salvador Aznar-Benitah, a specialist in chronobiology at the Institut de Recerca Biomèdica de Barcelona.
The RUVBL2 Enzyme, a Candidate for Developing Drugs That Act on Circadian Rhythms
In experiments using cell cultures and laboratory tissue samples, researchers identified cordycepin as a molecule capable of amplifying circadian cycles in skin cells and liver tissue. This small molecule can cross the blood-brain barrier and reach the brain. While administering cordycepin orally to mice had no effect, injecting it into the peritoneum – a membrane in the abdomen – amplified the mice’s circadian rhythms.
Mice treated with cordycepin exhibited increased activity during wakefulness, improved glucose control and metabolism, reduced weight gain on a high-fat diet, decreased markers of oxidation and inflammation, and improved muscle, cognitive, and cardiac function.
Analysis of epigenetic markers of aging revealed that cordycepin has an anti-aging effect. The intervention extended the median lifespan of the animals by 12%, increasing it from approximately 810 to 910 days.
Researchers demonstrated that cordycepin amplifies circadian rhythms by acting on the PVN within the hypothalamus, located in the lower part of the brain. In an adult human brain, the PVN occupies a volume of between 5 and 10 cubic millimeters (equivalent to a cube 2 millimeters on a side) and is estimated to contain between 50,000 and 100,000 neurons.
“It would be premature to describe cordycepin as a therapy,” cautioned Dapeng Ju. “In our research, it is a tool to demonstrate the concept that phenotypes associated with aging can be improved.”
Looking ahead to the development of future therapies, researchers showed that cordycepin amplifies circadian rhythms by activating the RUVBL2 enzyme. Blocking this enzyme eliminated all the beneficial effects of cordycepin on circadian rhythms, but restoring RUVBL2 restored the benefits. “RUVBL2 is an important circadian regulator,” said Dapeng Ju. “Its activity as an enzyme makes it a potentially attractive target for the future development of drugs.”
“The robustness of our internal clock decreases as we age, and this is one of the main causes of loss of functionality as we acquire older,” noted Salvador Aznar-Benitah. “This study provides us with a therapeutic route that allows us to reset our internal clock and realign it with the time of day so that our tissues perform their function at the right time of day.”
