All posts

The Science of Longevity: Exploring the Benefits of Longevity Supplements

Updated:
The Science of Longevity: Exploring the Benefits of Longevity Supplements

Introduction

Longevity, the timeless pursuit of a prolonged and vibrant life, fuels human curiosity and scientific exploration. Advancements in longevity science have unveiled promising avenues for extending our lifespan and improving our quality of life. One of these avenues is using supplements - a topic transforming how we approach aging. Ingredients obtained from fruits, vegetables, and indeed from within our bodies can contribute to the treatment of age-related ailments and improve longevity outcomes.

In this blog, we will explore the science behind some ingredients that have emerged as essential to longevity, including nicotinamide mononucleotide (NMN), resveratrol, fisetin, spermidine, vitamin D, and curcumin. Furthermore, we will explore some considerations to consider when deciding whether to use supplements and what lies ahead for longevity science. This blog aims to provide a comprehensive glimpse into the potential advantages of longevity supplements for your well-being and vitality.

Unlocking the Secrets of Longevity: An Overview

Pursuing longevity has evolved into a profound societal aspiration in the modern era. The desire to lead longer, healthier lives has ignited a global fascination, prompting a reimagination of aging and well-being. The field of longevity science, dedicated to understanding and extending the human lifespan, is currently experiencing a remarkable surge in research and breakthroughs. Recent years have witnessed significant progress, with discoveries centered around fundamental processes such as cellular senescence, epigenetic modifications, and genetic factors, that impact the rate of aging. Advances in regenerative medicine, precision nutrition, and personalized therapies have also contributed to this progress. Notable breakthroughs include the identification of specific genes associated with longevity, such as the FOXO and SIRT genes, as well as the exploration of caloric restriction mimetics and senolytic drugs to target aging-related cellular damage (1–4). The role of lifestyle factors, such as diet, exercise, and stress management, in promoting longevity has also gained substantial attention (5).

As a result of these advancements, life expectancy has shown a positive trajectory (6) (Figure 1). The shift towards health consciousness has contributed to this trend. While challenges remain, the convergence of cutting-edge research and a societal focus on health suggests a promising future for extending the human lifespan and promoting healthy aging.

Figure 1: Global life expectancy 2022. Based on data from the United Nations Population Division Estimates (6).

Certain compounds have emerged as potential longevity enhancements. Vitamin D, renowned for its role in bone health, is also being studied for its potential to mitigate age-related ailments (7). Curcumin, a bioactive compound found in turmeric, shows promise in supporting cellular health and combating oxidative stress (8). The realm of longevity science is in a constant state of evolution, continuously reinforcing the importance of molecules and supplements in retarding the aging process for both animals and humans. Resveratrol, NMN, Spermidine, and Fisetin are the primary constituents with scientifically substantiated capabilities to enhance longevity and promote overall health.

NMN: Fueling Cellular Energy

NMN is at the forefront of the longevity revolution, a molecule gaining traction for its pivotal role in cellular energy production through the nicotinamide adenine dinucleotide (NAD+) pathway. NAD+ is a coenzyme essential for various cellular processes, and its levels decline with age (9). NMN acts as a precursor to NAD+ and promotes the rejuvenation of this vital coenzyme, in turn reinvigorating cellular energy production (10).

Animal studies have shown that NMN supplementation can enhance mitochondrial function, the cellular powerhouses responsible for energy production, have a positive impact on cardiovascular health, improve age-related physiological markers, such as glucose tolerance, physical endurance, and muscle function, and improve DNA repair and integrity (10–14) (Figure 2). Furthermore, NMN may assist in protecting from neurodegenerative diseases, with animal studies indicating a protective role of NMN from oxidative stress, inflammation, and age-related damage (15). NMN has also been shown to enhance insulin sensitivity in prediabetic women, regulate glucose metabolism, and reduce inflammation, which are crucial factors in maintaining metabolic health (16).

Figure 2: Potential impact of NAD+ boosters such as NMN on human health via NAD+ signaling pathways (17).

Resveratrol: The Red Wine Molecule for Healthier Ageing

Nestled within the skin of red grapes lies a powerful longevity secret: resveratrol. This natural compound has intrigued researchers and health enthusiasts alike, driven by its likeness to the “French Paradox” – a phenomenon where moderate red wine consumption appears incongruent with lower cardiovascular risk (18) (Figure 3). Resveratrol is a type of STAC that stands for “Sirtuin Activating Compound” (19). Sirtuins are a protein that regulates various processes, including aging, metabolism, and stress responses (20). Resveratrol also exhibits antioxidant and anti-inflammatory properties, promoting cellular health by reducing harmful free radicals and modulating the inflammatory response (21). Research suggests that resveratrol might bolster heart health by promoting healthy blood vessel function, regulating blood pressure, and mitigating arterial stiffness (22). Moreover, resveratrol’s influence isn’t confined to the heart; emerging studies hint at its positive impact on cognitive function, potentially reducing cognitive decline (23).

 

Figure 3: Physiological and pathological effects of resveratrol in organisms. (18)

Fisetin: Nature’s Anti-Ageing Agent

Present in strawberries, apples, and onions, this plant-based flavonoid embodies a palette of potential benefits beyond its colorful origins (24) (Figure 4). Fisetin's prowess against aging unfolds through its capacity to counteract oxidative stress and inflammation, the dual forces driving the aging process (25). Fisetin also takes on the challenge of cellular senescence, where cells lose function and division capabilities. Recent studies propose that fisetin has seno-therapeutic activity in mice and human tissues, which may yield potential health benefits (26). A remarkable synergy has also emerged between fisetin and brain health. Its neuroprotective attributes have captivated researchers seeking cognitive preservation with age (27). Fisetin's influence on pathways related to neuronal resilience sparks optimism about its potential to safeguard mental acuity.

Figure 4: Concentration of fisetin measured in different vegetables and fruits (24).

Spermidine From Cellular Housekeeping to Longevity

Spermidine, a key player in cellular rejuvenation, operates through autophagy, which acts as cellular maintenance, clearing damaged components (28) (Figure 5). Spermidine enhances autophagy promoting cellular vitality and minimizing clutter. This mechanism shows potential in curbing age-related decline and preventing diseases. Research suggests spermidine's benefits, with animal studies indicating improved heart health and lifespan, and it is recommended as a potential therapeutic strategy for neurological disorders (29–31).

Figure 5: The impact of spermidine on the aging process and cardiovascular well-being. (a): As individuals age, the susceptibility to cardiovascular ailments rises, leading to heightened hypertrophy and diminished diastolic function. (b) Research has shown that administering spermidine through diet to mice mitigates the likelihood of cardiovascular disease (CVD) and mortality as they age. This effect is attributed to heightened autophagy, enhancing cardiomyocyte fitness, and reducing the risk of CVD and age-related death (28).

Choosing the Right Longevity Supplements: Considerations and Precautions

When choosing longevity supplements, practicality should guide your decisions. Prioritize reputable sources that adhere to rigorous testing and quality standards. Combining various supplements, including vitamins, can complement your overall well-being effectively. However, their impact is fully maximized when integrated with a balanced lifestyle. Incorporate them into a healthy diet, regular exercise, and sensible daily habits. Evaluating the levels of vitamins and minerals gained from your diet is also recommended. If you are receiving sufficient levels, then there may be less need to utilize supplements. 

The Future of Longevity Science: What Lies Ahead

In the realm of longevity science, promising research areas have unfolded. Among these, senolytics and gene therapy have emerged as potential treatments for longevity support. Researchers have identified and tested several senolytic agents that exhibit remarkable efficacy in preclinical studies, demonstrating their capacity to mitigate age-related decline and improve tissue function. These agents can alleviate chronic conditions like osteoarthritis and pulmonary fibrosis (4,32). Research into gene therapy for longevity has opened unprecedented avenues for manipulating our genetic blueprint to potentially extend the human lifespan and enhance overall health span. Gene therapy involves the targeted alteration of genes to address genetic disorders, and scientists are now exploring its application to influence aging processes and treat age-related diseases (33). Another treatment known as rapamycin, an mTOR inhibitor, has also emerged as a promising treatment; however, it is important to note that it is prescription only and requires a doctor’s consultation before use (34).

Conclusion

In summary, our exploration into longevity supplements has illuminated the potential of key ingredients—NMN, resveratrol, fisetin, and spermidine—to bolster longevity and overall well-being. NMN's role in cellular energy production rejuvenates vitality, while resveratrol's multifaceted benefits extend from cardiovascular health to cognitive preservation. Fisetin's anti-aging prowess and its synergy with brain health highlight its promise. Spermidine's cellular maintenance mechanisms can potentially prevent age-related decline and diseases. In our quest for healthier, more fulfilling lives, informed choices are paramount. Prioritize reputable sources and consult experts when considering supplementation. By staying attuned to cutting-edge research, we empower ourselves to make proactive strides toward longevity.

If you want to optimize your health and longevity, check out the MASI Premium range of longevity supplements. MASI provide NMN to help restore cellular vitality, Resveratrol to fight against oxidative stress, Spermidine to help fight aging by restoring the healthy process of autophagy in the body, and Fisetin to help our bodies maintain their youthful vitality by eliminating harmful senescent cells that promote the aging process.

Author Biography

This article was written by Dr. Sarah King (PhD). Dr King is a longevity researcher who specialised in molecular and cellular biology, specifically cell aging and fate as related to NAD signalling during her PhD. She is also a senior medical writer for Co-Labb.

References

  1. Martins R, Lithgow GJ, Link W. Long live FOXO : unraveling the role of FOXO proteins in aging and longevity. Aging Cell. 2016 Apr;15(2):196–207.
  2. Zhao L, Cao J, Hu K, He X, Yun D, Tong T, et al. Sirtuins and their Biological Relevance in Aging and Age-Related Diseases. Aging Dis. 2020;11(4):927.
  3. Shintani T, Shintani H, Sato M, Ashida H. Calorie restriction mimetic drugs could favorably influence gut microbiota leading to lifespan extension. GeroScience [Internet]. 2023 Jun 30 [cited 2023 Aug 16]; Available from: https://link.springer.com/10.1007/s11357-023-00851-0
  4. Nambiar A, Kellogg D, Justice J, Goros M, Gelfond J, Pascual R, et al. Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability. eBioMedicine. 2023 Apr;90:104481.
  5. Dyer KA. Daily healthy habits to reduce stress and increase longevity. J Interprofessional Educ Pract. 2023 Mar;30:100593.
  6. United Nations Population Division. World Population Prospects 2022 [Internet]. Available from: https://population.un.org/wpp/Download/Standard/Mortality/
  7. Bruyère O, Cavalier E, Souberbielle JC, Bischoff-Ferrari HA, Beaudart C, Buckinx F, et al. Effects of vitamin D in the elderly population: current status and perspectives. Arch Public Health. 2014 Dec;72(1):32.
  8. Bielak-Zmijewska A, Grabowska W, Ciolko A, Bojko A, Mosieniak G, Bijoch Ł, et al. The Role of Curcumin in the Modulation of Ageing. Int J Mol Sci. 2019 Mar 12;20(5):1239.
  9. Schultz MB, Sinclair DA. Why NAD + Declines during Aging: It’s Destroyed. Cell Metab. 2016 Jun;23(6):965–6.
  10. Shade C. The Science Behind NMN—A Stable, Reliable NAD+ Activator and Anti-Aging Molecule. Integr Med. 2020;19(1):12–4.
  11. Whitson JA, Bitto A, Zhang H, Sweetwyne MT, Coig R, Bhayana S, et al. SS‐31 and NMN: Two paths to improve metabolism and function in aged hearts. Aging Cell [Internet]. 2020 Oct [cited 2023 Aug 15];19(10). Available from: https://onlinelibrary.wiley.com/doi/10.1111/acel.13213
  12. Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr. 2021 Jan 2;18(1):54.
  13. Klimova N, Long A, Kristian T. Nicotinamide mononucleotide alters mitochondrial dynamics by SIRT3‐dependent mechanism in male mice. J Neurosci Res. 2019 Aug;97(8):975–90.
  14. Hong W, Mo F, Zhang Z, Huang M, Wei X. Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Front Cell Dev Biol. 2020 Apr 28;8:246.
  15. Ramanathan C, Lackie T, Williams DH, Simone PS, Zhang Y, Bloomer RJ. Oral Administration of Nicotinamide Mononucleotide Increases Nicotinamide Adenine Dinucleotide Level in an Animal Brain. Nutrients. 2022 Jan 12;14(2):300.
  16. Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021 Jun 11;372(6547):1224–9.
  17. Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018 Mar;27(3):529–47.
  18. Catalgol B, Batirel S, Taga Y, Ozer NK. Resveratrol: French Paradox Revisited. Front Pharmacol [Internet]. 2012 [cited 2023 Aug 15];3. Available from: http://journal.frontiersin.org/article/10.3389/fphar.2012.00141/abstract
  19. Curry AM, White DS, Donu D, Cen Y. Human Sirtuin Regulators: The “Success” Stories. Front Physiol. 2021 Oct 21;12:752117.
  20. Grabowska W, Sikora E, Bielak-Zmijewska A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology. 2017 Aug;18(4):447–76.
  21. Meng T, Xiao D, Muhammed A, Deng J, Chen L, He J. Anti-Inflammatory Action and Mechanisms of Resveratrol. Molecules. 2021 Jan 5;26(1):229.
  22. Dyck G, Raj P, Zieroth S, Dyck J, Ezekowitz J. The Effects of Resveratrol in Patients with Cardiovascular Disease and Heart Failure: A Narrative Review. Int J Mol Sci. 2019 Feb 19;20(4):904.
  23. Cicero AFG, Ruscica M, Banach M. Resveratrol and cognitive decline: a clinician perspective. Arch Med Sci. 2019;15(4):936–43.
  24. Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: A Dietary Antioxidant for Health Promotion. Antioxid Redox Signal. 2013 Jul 10;19(2):151–62.
  25. Jiang K, Yang J, Xue G, Dai A, Wu H. Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis. J Inflamm Res. 2021 Jul;Volume 14:2963–78.
  26. Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018 Oct;36:18–28.
  27. Hassan SSU, Samanta S, Dash R, Karpiński TM, Habibi E, Sadiq A, et al. The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress. Front Pharmacol. 2022 Oct 10;13:1015835.
  28. Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010 May;221(1):3–12.
  29. De Cabo R, Navas P. Spermidine to the rescue for an aging heart. Nat Med. 2016 Dec;22(12):1389–90.
  30. Filfan M, Olaru A, Udristoiu I, Margaritescu C, Petcu E, Hermann DM, et al. Long-term treatment with spermidine increases health span of middle-aged Sprague-Dawley male rats. GeroScience. 2020 Jun;42(3):937–49.
  31. Ghosh I, Sankhe R, Mudgal J, Arora D, Nampoothiri M. Spermidine, an autophagy inducer, as a therapeutic strategy in neurological disorders. Neuropeptides. 2020 Oct;83:102083.
  32. Gil TH, Zheng H, Lee HG, Shin JW, Hwang SW, Jang KM, et al. Senolytic drugs relieve pain by reducing peripheral nociceptive signaling without modifying joint tissue damage in spontaneous osteoarthritis. Aging. 2022 Aug 15;14(15):6006–27.
  33. Yu J, Li T, Zhu J. Gene Therapy Strategies Targeting Aging-Related Diseases. Aging Dis. 2022;0.
  34. Mannick JB, Lamming DW. Targeting the biology of aging with mTOR inhibitors. Nat Aging. 2023 May 4;3(6):642–60.
Written and Reviewed by: MASI ANTI-AGING SCIENCE