Cutting-edge trends in longevity ingredients

Aging is a complex physiological phenomenon. As defined by the World Health Organisation (WHO), it is an "irreversible, progressive, and universal decline in the function of multiple-system organs." By 2030, an estimated one in six individuals globally will be 60 years old or older. The concept of anti-aging has evolved beyond merely extending lifespan; it now emphasises promoting a healthier, more youthful quality of life, focusing on extending healthspan and rejuvenating vitality. In this article, we will delve into four advanced longevity ingredients from Bonerge.

1. Fisetin: the most promising natural senolytic for cellular homeostasis

Cellular senescence is a crucial biomarker of aging. Senescent cells enter an irreversible state of cell-cycle arrest, accompanied by significant changes in cell morphology, function, and secretory profiles. As age progresses, these senescent cells gradually accumulate in tissues and organs. Excessive senescent cells secrete the senescence-associated secretory phenotype (SASP), which disrupts cellular homeostasis, induces chronic inflammation, and impairs the body's immune surveillance mechanism¹. This, in turn, triggers tissue dysfunction and the development of various age-related health issues.

Fisetin, a plant-derived flavonoid, is naturally present in numerous fruits and vegetables, such as strawberries, apples, and persimmons. Since 2018, research from leading institutions has identified fisetin as a powerful senotherapeutic agent with two complementary modes of action^2-3:

• Senoprevention: Reducing senescent cell formation

Fisetin activates the AMPK signalling pathway, suppresses the over-activation of the mTOR pathway, and diminishes reactive oxygen species (ROS) accumulation due to its excellent antioxidant properties. These actions effectively lower the probability of senescence onset.

• Senolysis: Selective clearance of senescent cells

Fisetin selectively induces apoptosis or autophagy in senescent cells by inhibiting the p53/p21 signalling pathway. Comparative studies have demonstrated that fisetin outperforms other senolytic agents like quercetin, resveratrol, and curcumin, achieving over 68% clearance of senescent cells without harming healthy cells. 

In pre-clinical models, fisetin has been shown to reduce the burden of senescent cells in multiple tissues, including the liver, lungs, and brain, leading to improvements in overall health and lifespan⁴.

BeFisetin®: setting the gold standard for Fisetin

BeFisetin® has established a new paradigm for the quality and safety of fisetin ingredients. Through three years of meticulous optimisation, BeFisetin® has formulated robust quality standards. Notably, it is the first fisetin ingredient to obtain SA-GRAS certification, representing the highest-quality fisetin raw material in the industry.

2. Urolithin A: promoting the natural recycling of NAD+

A decline in NAD+ (Nicotinamide Adenine Dinucleotide) levels is a key indicator of the aging process. NAD+ is an essential coenzyme in the tricarboxylic acid cycle, facilitating sugar, fat, and amino-acid metabolism and energy production. It plays a pivotal role in cell metabolism, anti-aging processes, and energy homeostasis.

Urolithin A (UA) is a natural metabolite generated by gut microorganisms from ellagic acid and its derivatives. Research has demonstrated that UA supplementation can elevate NAD+ levels. It is capable of enhancing the internal cyclic metabolism of NAD, regulating intracellular NAD+ levels^5-6. In this way, it forms a feedback regulatory loop, thereby facilitating the natural recycling of NAD+.

• Urolithin A significantly elevates NAD+ levels

Studies have shown that UA supplementation can substantially increase NAD+ levels in the body. Animal research indicates an up to 50% increase in NAD+ levels. Notably, its ability to boost NAD+ is comparable to a 5-fold dose of the NAD precursor Nicotinamide Riboside (NR)⁵.

• Urolithin A enhances Sirt1 expression

Unlike direct supplementation of NAD precursors, UA increase NAD+ levels by activating SIRT. In mouse experiments, UA supplementation significantly upregulated the expression of SIRT1. SIRT1 promotes the expression of NAMPT, a key rate-limiting enzyme in the NAD+ salvage biosynthesis pathway that catalyzes the conversion of NAM to NMN, thus facilitating NAD+ synthesis⁶.

StanYouth®standing by youth with Urolithin A

StanYouth® is a high-quality branded Urolithin A ingredient, with comprehensive validation demonstrating 99% high purity. Produced through a patented process, StanYouth® strives for excellence in all quality metrics, including color, purity, density, residual solvents, heavy metals, microorganism etc.

3. S-Equol: the new generation of women's health supplement

Menopause is a natural stage in a woman's life characterised by ovarian decline and reduced estrogen levels. This often leads to symptoms such as hot flashes, night sweats, mood swings, and sleep disturbances. While hormone replacement therapy (HRT) can alleviate these symptoms, long-term use increases the risk of breast cancer by 26% and cardiovascular events by 29%⁷. Therefore, safer alternatives are urgently needed.

In the supplements market, among the common menopause supplements are soy isoflavones. These substances bind to ERβ and imitate estrogenic activity without significant side effects. S-equol, a metabolite derived from soy isoflavones, also emulates estrogenic functions. In vitro research reveals that S-equol exhibits greater permeability across the gastrointestinal tract and the blood-brain barrier (BBB) compared to soy glycosides or genistein flavonoids. Considering these characteristics, S-equol emerges as a more favourable option for promoting menopause-related health⁸.

In a double-blind, placebo-controlled trial involving menopausal women, when administered at a daily dose of 10mg for 12 weeks, S-equol significantly reduced the frequency of hot flashes by 58.7%. The severity of neck or shoulder muscle stiffness also decreased significantly in the S-equol group. In contrast, women receiving a placebo only experienced a 34.5% reduction⁹.

BongeLov® S-Equol: superior equol for menopausal health

Equol exists in two chiral forms, R-equol and S-equol. Fecal bacteria produce S-equol as the primary metabolite of soy isoflavone. BongeLov® S-equol is produced through a patented fermentation process. Leveraging its innovative patented technology, BongeLov® S-equol has achieved an ultra-high enantiomeric purity of over 99%. This exceptional quality not only ensures product quality stability but also strongly guarantees its biological activity, enabling the active ingredient to fully exert its physiological functions.

Summary

Dietary supplements are evolving from a "broad-functionality" approach to "precision-targeting of niche markets." Understanding the mechanisms of ingredients is the cornerstone of research and development. Bonerge's ingredient portfolio aligns with this trend, providing core technological support for anti-aging foods, skincare products, and medical-grade solutions by targeting different aging pathways.

About Bonerge

Bonerge Lifescience is an innovative manufacturer that offers comprehensive turnkey solutions in the nutraceutical and cosmeceutical ingredients industries. Committed to scientific rigor and quality assurance, Bonerge is at the forefront of healthspan optimisation, pioneering promising longevity ingredients such as Fisetin, Urolithin A, S-equol, Dihydroberberine, Pyrroloquinoline Quinone (PQQ), and L-Ergothionine. Through groundbreaking research and next-generation solutions, Bonerge is shaping the future of healthy aging.

Contact us at kim.c@bonerge.com to explore how we can collaborate.

Reference：

1. Lunin, S. M.; et al. (2022).  Cell Senescence and Central Regulators of Immune Response.  International journal of molecular sciences. 23(8), 4109.
2. Zhang, L.; et al. (2020).  Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence.  Frontiers in pharmacology. 11, 553690.
3. Yutong, G.; et al. (2021).  Fisetin Inhibits Doxorubicin-induced Senescence of Pulmonary Artery Endothelial Cells Through Nrf2/HO-1 and MAPK Signaling Pathways . Journal of Huazhong University of Science and Technology (Medical Science). 50(06), 685-692.
4. Yousefzadeh, Matthew J et al. “Fisetin is a senotherapeutic that extends health and lifespan.” EBioMedicine vol. 36 (2018): 18-28. doi:10.1016/j.ebiom.2018.09.015
5. Zhu, H.; et al,  Urolithin A Ameliorates Athletic Ability and Intestinal Microbiota in Sleep Deprivation from the Perspective of the Gut-Muscle Axis.  Mol Nutr Food Res. 2024;68(7):e2300599.
6. Ghosh, N.; et al.  Urolithin A augments angiogenic pathways in skeletal muscle by bolstering NAD+ and SIRT1.  Sci Rep. 2020;10(1):20184.
7. Rossouw JE, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomised controlled trial. JAMA (2002). DOI:10.1001/jama.288.3.321.
8. Sekikawa, Akira et al. “Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia.” International journal of molecular sciences vol. 23,19 11921. 7 Oct. 2022, doi:10.3390/ijms231911921
9. Sekikawa, Akira et al. “Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia.” International journal of molecular sciences vol. 23,19 11921. 7 Oct. 2022, doi:10.3390/ijms231911921