As society progresses and our understanding of aging evolves, various anti-aging strategies continue to emerge.

However, regardless of the method, three fundamental factors remain essential: sleep, diet, and exercise. Scientific research has confirmed that these elements, as regenerative medicine adjuvants, play a crucial role in slowing down aging.¹ Yet, sleep disorders have become a major health concern across all age groups.

Adults suffer from poor sleep due to social pressures, heavy workloads, and unhealthy lifestyles, while older adults experience declining sleep quality due to illness and medication use.² Younger individuals are particularly prone to chronic sleep deprivation and circadian rhythm disruptions, making circadian rhythm a key aspect of sleep improvement.³

Circadian rhythm regulation: The foundation of healthspan

Sleep quality is closely linked to the biological clock, an internal mechanism that regulates physiological and behavioral activities in alignment with environmental cycles. Among these rhythms, the circadian rhythm is particularly critical and is influenced by factors such as light exposure, food intake, stress levels, physical activity, and social environment.⁴

However, as people age, the precision and stability of their biological clock gradually decline. This manifests in lengthened circadian gene oscillation cycles and reduced amplitude.

Studies indicate that older adults frequently experience an ‘advanced phase shift’, where their sleep and wake times occur one to two hours earlier than younger individuals.⁵ This reflects intrinsic changes in the biological clock rather than mere behavioral adjustments.

Additionally, the amplitude of circadian rhythms in melatonin and cortisol diminishes significantly, potentially increasing the risk of metabolic disorders, neurodegenerative diseases, and other health issues.⁵

Urolithin A: A novel regulator of cellular circadian rhythm

A 2024 study suggests that Urolithin A can regulate circadian rhythms in various cell types, effectively improving sleep quality, and mitigating modern lifestyle-induced ‘social jet-lag’, such as shift work, jet lag, and irregular sleep schedules.⁶

✨ Urolithin A regulates intestinal barrier circadian rhythm

Research demonstrates that Urolithin A influences the mRNA expression rhythms of clock genes in Caco-2 cells, affecting expression levels, amplitude, phase peaks, and curve fitting.⁶ Both in vitro and in vivo models indicate that Urolithin A can restore circadian rhythm disturbances caused by inflammation induced by TNF-α and IL-17A, improving the rhythmic expression of tight junction and clock genes.

✨ Urolithin A improves circadian regulation in senescent cells

Experimental data shows that Urolithin A enhances the amplitude of Bmal1 expression in senescent cells.⁷ The underlying mechanism likely involves the stabilization of SIRT1 protein, enhancing its deacetylation activity, which promotes PER2 deacetylation and degradation.⁷ This, in turn, modulates CLOCK/BMAL1 activity and reinforces BMAL1 rhythmic expression.⁷

Enhancing energy during the day, improving sleep at night

Unlike melatonin supplementation, which can be linked to grogginess, excessive drowsiness or dizziness upon waking, Urolithin A supports sleep quality without these effects.⁸

Animal studies demonstrate that Urolithin A improves cellular energy levels and enhances grip strength in sleep-deprived mice, outperforming caffeine in this regard.⁷ This effect is likely attributed to Urolithin A’s ability to boost NAD+ levels and activate SIRT1, thereby maintaining cellular energy homeostasis.⁹

NAD+ is a crucial coenzyme for cellular metabolism and energy balance. A 2020 study shows that Urolithin A supplementation can significantly elevate NAD+ levels, with animal studies indicating an increase of up to 50%. Notably, its NAD+ boosting capability is comparable to a fivefold dose of nicotinamide riboside (NR).¹⁰

Furthermore, Urolithin A activates SIRT1, a NAD+-dependent deacetylase that plays a pivotal role in cellular stress responses and metabolic regulation. Like other NAD+ precursors such as nicotinamide mononucleotide (NMN) and NR, Urolithin A exerts its health benefits by enhancing SIRT1 activity.¹¹

Urolithin A has been scientifically validated for its multiple health benefits, making it a premium ingredient choice for dietary supplements.

Figure 1: Potential health benefits of Urolithin A.¹²⁻¹⁷

Ongoing clinical research: Unlocking the full potential of Urolithin A

Urolithin A is a naturally occurring metabolite produced by gut microbiota from dietary ellagitannins found in fruits such as pomegranates and certain nuts. With its growing recognition for health benefits, its quality and standardization can be a challenge.

A 2024 study conducted by the National University of Singapore analyzed five commercially available Urolithin A supplements and found significant discrepancies between labeled and actual ingredient content, with deviations ranging from -15.5% to +28.6%.¹⁸ This variation is likely due to the lack of standardized quality control measures in the relatively new Urolithin A market.

Figure 2: Urolithin A comparison from different sources

Pioneering high-quality Urolithin A development

Bonerge, a leader in longevity ingredient innovation, was among the earliest manufacturers to invest in Urolithin A research and production. After three years of process optimization, Bonerge has established rigorous quality standards and launched StanYouth Urolithin A, ensuring superior ingredient purity and efficacy.

Figure 3: StanYouth Urolithin A

Beyond raw material quality, Bonerge is actively advancing clinical research on Urolithin A. In October 2024, the company initiated clinical trials exploring its potential applications in skin health and anti-aging, with results expected in February 2025.

Figure 4: Ongoing beauty-from-within supplementation clinical trial

Urolithin A is poised to become a cornerstone in health management and longevity science. As consumers increasingly seek clinically validated, high-quality supplements, industry leaders like Bonerge continue to drive innovation.

Beyond Urolithin A, Bonerge has also introduced other promising longevity ingredients such as Fisetin, and S-equol, further expanding the frontiers of health optimization. By maintaining a commitment to scientific rigor and quality assurance, Bonerge is shaping the future of healthspan enhancement through groundbreaking research and next-generation longevity solutions.

References

[1] Ghanemi, A.; et al. Medicines. 2022; 9(1):7.
[2] Grandner, M.; et al. Aging Health. 2012; 8(3): 219-221.
[3] Sandalova, E.; et al. GeroScience. 2024; 46(5): 5075-5083.
[4] Zitting, K.M.; et al. Sci Rep. 2018; 8(1):11052.
[5] National Institute of General Medical Sciences. Circadian Rhythms.
[6] Hood, S.; et al. J Clin Invest. 2017; 127(2):437-446.
[7] Du, Y.; et al. Nutrients. 2024; 16(14):2263.
[8] Kuatov, R.; et al. Nutrients. 2025; 17(1):20.
[9] Mayo Clinic. Adult Health.
[10] Zhu, H.; et al. Mol Nutr Food Res. 2024; 68(7):e2300599.
[11] Ghosh, N.; et al. Sci Rep. 2020; 10(1):20184.
[12] Guo, X.; et al. Sci Rep. 2012; 2:640.
[13] Yasuda, T.; et al. Sci Rep. 2024; 14(1):15706.
[14] Yu, Z.H.; et al. J Agric Food Chem. 2022; 70(38):11981-11993.
[15] Tao, H.; et al. Front Pharmacol. 2022; 13:875611.
[16] Liu, J.; et al. Tissue Eng Regen Med. 2022; 19(1):151-159.
[17] Feng, Z.H.; et al. Front Pharmacol. 2022; 13:806284.
[18] Jiao, P.; et al. Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(8):5765-5777.

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