As science gains a better understanding of the ageing process, a fascinating group of proteins called sirtuins is coming to the fore in longevity research. Although they work behind the scenes, they are among the most important regulators of cellular health and ageing processes. They can be described as invisible guardians of youth, watching over our metabolism, immunity and DNA integrity.
In this article, we will take a closer look at what sirtuins are, what role they play in the body and, most importantly, how we can naturally activate their action using current scientific knowledge and lifestyle strategies.
What are sirtuins?
Sirtuins are a family of seven enzymes (SIRT1–SIRT7) that act as NAD⁺-dependent deacetylases. They work by modifying other proteins by removing acetyl groups, which changes the activity of these proteins and thus affects many biological processes.
The best-known member of this family is SIRT1, which is involved in, among other things:
- gene expression regulation,
- DNA repair,
- lipid and glucose metabolism,
- mitochondrial function,
- protection against oxidative stress,
- maintaining energy homeostasis,
- control of the circadian rhythm (together with the CLOCK and BMAL1 proteins) [1][2].
Importantly, the activity of sirtuins is strongly dependent on the level of NAD⁺, a molecule whose amount in the body decreases with age. It is the decline in NAD⁺ that leads, among other things, to a reduction in the effectiveness of DNA repair, mitochondrial dysfunction and an increased risk of lifestyle diseases such as type 2 diabetes, atherosclerosis and neurodegenerative diseases [3].
How to activate sirtuins naturally?
Knowing how important sirtuin activity is for health and longevity, the key question becomes: how can we support them on a daily basis? It turns out that there are several proven methods – based on lifestyle and supplementation – that can increase their expression and enzymatic activity.
One of the most documented strategies is calorie restriction, especially in the form of intermittent fasting. Numerous studies have shown that periodic fasting (e.g. 16:8 or 20:4) increases NAD⁺ levels, leading to SIRT1 activation and improved cellular immunity[4]. This mechanism is similar to that of calorie restriction, which is known to prolong life in studies on many species, from yeast to mice to primates [5].
Physical activity, especially aerobic exercise, is an equally effective stimulus. Regular exercise stimulates NAD⁺ production and sirtuin activation in muscle tissue, which improves metabolism, insulin sensitivity and mitochondrial function. It has also been proven that active people have higher levels of SIRT1 in their blood and a lower risk of age-related diseases [6].
Diet is equally important, especially one rich in natural compounds that activate sirtuins, known as polyphenols. The best known is resveratrol, found in grape skins and red wine. It works by directly activating SIRT1 and increasing the expression of protective genes. However, supplementation is necessary to achieve therapeutic effects, as the doses present in the diet are too low [7].
Supplements supporting sirtuin activation
With the development of biotechnology, specific supplements have also emerged that can effectively support sirtuins, both indirectly (by increasing NAD⁺) and directly:
- Nicotinamide Riboside (NR) – a precursor of NAD⁺ with very good bioavailability. NR supplementation increases NAD⁺ levels in the blood, which in turn activates SIRT1 and improves mitochondrial function. In human studies, NR improved markers of metabolic and mitochondrial health [8][9].
- Trans-Resveratrol – a powerful antioxidant and one of the most studied SIRT1 activators. In combination with NR, it works synergistically: resveratrol activates sirtuins, and NR provides them with ‘fuel’ in the form of NAD⁺ [10].
- Spermidine – although it does not act directly on sirtuins, it supports autophagy and the expression of longevity genes, which has a positive effect on overall cellular homeostasis [11].
- Apigenin – a natural flavonoid found in parsley and chamomile, among others, which blocks the enzyme CD38 responsible for the degradation of NAD⁺. This helps maintain high levels of NAD⁺ and indirectly supports sirtuins [12].
- Coenzyme Q10 (ubiquinol) – although it does not directly affect sirtuin expression, it supports the mitochondria, which are one of the main targets of these enzymes [13].
Conclusions: youth is a strategy, not a coincidence
Sirtuins are now recognised as key therapeutic targets in the context of longevity. Their activity affects almost every aspect of cellular health: from DNA repair, through metabolism, to the regulation of oxidative stress and circadian rhythms. The good news? We have partial control over their activation – all we need to do is implement proven strategies: intermittent fasting, physical activity, a diet rich in polyphenols and supplementary supplementation.
At LLMe, we combine the latest knowledge with practical solutions. Supplements such as NR, Resveratrol, Spermidine and Apigenin are not marketing gimmicks – they provide real support for your internal ‘youth system’.
References:
- Haigis MC, Sinclair DA. Mammalian Sirtuins: Biological Insights and Disease Relevance. Annu Rev Pathol. 2010;5:253–95.
https://doi.org/10.1146/annurev.pathol.4.110807.092250 - Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab. 2014;25(3):138–45.
https://doi.org/10.1016/j.tem.2013.12.001 - Verdin E. NAD⁺ in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208–13.
https://doi.org/10.1126/science.aac4854 - Canto C, Auwerx J. Caloric restriction, SIRT1 and longevity. Trends Endocrinol Metab. 2009;20(7):325–31.
https://doi.org/10.1016/j.tem.2009.03.008 - Fontana L, Partridge L, Longo VD. Extending healthy life span—from yeast to humans. Science. 2010;328(5976):321–6.
https://doi.org/10.1126/science.1172539 - Greig FH et al. Exercise and sirtuins: a double advantage on age-related disorders? Ageing Res Rev. 2015;24(Pt B):229–38.
https://doi.org/10.1016/j.arr.2015.08.004 - Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5(6):493–506.
https://doi.org/10.1038/nrd2060 - Trammell SAJ et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7:12948.
https://doi.org/10.1038/ncomms12948 - Martens CR et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD⁺ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286.
https://doi.org/10.1038/s41467-018-03421-7 - Timmers S et al. Calorie restriction-like effects of 30 days of resveratrol supplementation. Cell Metab. 2011;14(5):612–22.
https://doi.org/10.1016/j.cmet.2011.10.002 - Madeo F et al. Spermidine in health and disease. Science. 2018;359(6374):eaan2788.
https://doi.org/10.1126/science.aan2788 - Covarrubias AJ et al. The NAD⁺ metabolism and the control of aging and longevity. Trends Biochem Sci. 2021;46(4):283–295.
https://doi.org/10.1016/j.tibs.2020.10.006 - Littarru GP, Tiano L. Clinical aspects of coenzyme Q10: An update. Nutrition. 2010;26(3):250–4.
https://doi.org/10.1016/j.nut.2009.08.008