Sirtuins – silent guardians of youth

As science increasingly understands aging processes, a fascinating group of proteins has come to the forefront of longevity research – sirtuins. Although they work in hiding, they are among the most important regulators of cellular health and aging processes. We can say they are invisible guardians of youth that watch over our metabolism, immunity, and DNA integrity.

In this article, we will take a closer look at what sirtuins are, what their role in the body is, and – most importantly – how we can naturally activate their function, 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. Their action involves 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 participates in:

  • regulation of gene expression,
  • DNA damage repair,
  • lipid and glucose metabolism,
  • mitochondrial function,
  • protection against oxidative stress,
  • maintenance of energy homeostasis,
  • control of circadian rhythm (together with CLOCK and BMAL1 proteins) [1][2].

Importantly, sirtuin activity is strongly dependent on the level of NAD – a molecule whose amount in the body decreases with age. It is precisely the decline in NAD that leads to reduced DNA repair efficiency, mitochondrial dysfunction, and increased risk of lifestyle diseases such as type 2 diabetes, atherosclerosis, or 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 daily? It turns out there are several proven methods – based on lifestyle and supplementation – that allow us to increase their expression and enzymatic activity.

One of the most well-documented strategies is caloric 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, which leads to SIRT1 activation and improved cellular resilience[4]. This mechanism resembles the action of caloric restriction, known for extending lifespan in studies across many species – from yeast, through mice, to primates [5].

woman training with ropes

Equally effective stimulus is physical activity, especially aerobic in nature. Regular exercise stimulates NAD⁺ production and sirtuin activation in muscle tissue, improving metabolism, insulin sensitivity, and mitochondrial function. It has also been proven that active individuals have higher SIRT1 levels in blood and lower risk of age-related diseases [6].

    Equally important is diet – especially rich in natural sirtuin-activating compounds, i.e., polyphenols. The most famous is resveratrol, present in grape skins and red wine. Its action involves direct SIRT1 activation, as well as increased expression of protective genes. However, to achieve therapeutic effects, supplementation is necessary – because dietary doses are too low [7].

    Supplements supporting sirtuin activation

    With the development of biotechnology, specific supplements have emerged that can effectively support sirtuins, both indirectly (by increasing NAD) and directly:

    • Nicotinamide Riboside (NR) – NAD⁺ precursor with very good bioavailability. NR supplementation increases NAD⁺ levels in 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 – powerful antioxidant and one of the most frequently studied SIRT1 activators. Combined with NR, it acts synergistically: resveratrol activates sirtuins, and NR provides them with "fuel" in the form of NAD⁺ [10].
    • Spermidine – although it doesn't act directly on sirtuins, it supports autophagy and longevity gene expression, positively affecting overall cellular homeostasis [11].
    • Apigenin – natural flavonoid found in parsley and chamomile, which blocks the CD38 enzyme – responsible for NAD⁺ degradation. This helps maintain high NAD⁺ levels and indirectly supports sirtuins [12].
    • Coenzyme Q10 (ubiquinol) – although it doesn't directly affect sirtuin expression, it supports mitochondria, which are one of the main targets of these enzymes [13].

    Conclusions: youth is strategy, not chance

    Sirtuins are now recognized as key therapeutic targets in the context of longevity. Their activity affects nearly every aspect of cellular health: from DNA repair, through metabolism, to regulation of oxidative stress and circadian rhythm. Good news? We have partial control over their activation – just implement proven strategies: intermittent fasting, physical activity, diet rich in polyphenols, and complementary supplementation.

    At LLMe, we combine the latest knowledge with practical solutions. Supplements such as NR, Resveratrol, Spermidine, or Apigenin are not marketing – they are real support for your internal "youth system".

    Bibliography and sources

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      https://doi.org/10.1146/annurev.pathol.4.110807.092250
    2. 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
    3. Verdin E. NAD⁺ in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208–13.
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    4. Canto C, Auwerx J. Caloric restriction, SIRT1 and longevity. Trends Endocrinol Metab. 2009;20(7):325–31.
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    5. Fontana L, Partridge L, Longo VD. Extending healthy life span—from yeast to humans. Science. 2010;328(5976):321–6.
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    6. 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
    7. 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
    8. 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
    9. 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
    10. 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
    11. Madeo F et al. Spermidine in health and disease. Science. 2018;359(6374):eaan2788.
      https://doi.org/10.1126/science.aan2788
    12. 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
    13. 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
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    This text was developed with the support of OpenAI (ChatGPT) artificial intelligence, based on a broad review of scientific research and available sources in medical and popular science literature.
    This article is for informational purposes only and does not replace medical advice. Consult a specialist before starting supplementation.