What does the research say about sirtuins?

Sirtuins are a family of histone deacetylase enzymes that depend on nicotinamide adenine dinucleotide (NAD+) for their catalytic activity. In the research literature they are referred to by the abbreviation SIRT, with individual family members numbered; SIRT1 and SIRT3 are the members most frequently named in the metabolic and mitochondrial work covered here. They are classified as histone deacetylases and are grouped with telomerase, matrix metalloproteinases, antioxidant enzymes, CD44, tyrosinase, microphthalmia-associated transcription factor and melanocortin receptors among the molecular targets reviewed in modern cosmetic science, where they are discussed in relation to DNA repair and gene expression [1]. The evidence block supplied for this page does not give a sequence, molecular formula or molecular weight for any sirtuin, so none is stated here.

The work centres on the sirtuin family as a node within nutrient-sensing and NAD+-dependent signalling, particularly the SIRT1 and SIRT3 members and their involvement in mitochondrial biogenesis, energy expenditure, oxidative metabolism and insulin sensitivity [2].

Research Studies

Sirtuins as molecular targets in skin biology research

A review of molecular targets in modern cosmetic science lists histone deacetylases, and sirtuins in particular, alongside telomerase, matrix metalloproteinases, antioxidant enzymes, CD44, tyrosinase, microphthalmia-associated transcription factor and melanocortin receptors. The review frames these macromolecules as points of targeted modulation in research on skin aging, pigmentation, inflammation and tissue regeneration, and links them to processes including DNA repair and gene expression [1]. This is a review of targets rather than a report of an intervention in a defined population.

Sirtuin activation and metabolic endpoints in obesity research

A registered trial record describes obesity as a chronic, multifactorial disease with metabolic, cardiovascular and psychosocial complications, and notes that long-term effectiveness of lifestyle-based weight-management strategies remains limited. It identifies the sirtuin family, particularly SIRT1 and SIRT3, as a target of interest because of involvement in mitochondrial biogenesis, energy expenditure, oxidative metabolism and regulation of insulin sensitivity, and refers to bioactive compounds that activate sirtuins, including nicotinamide riboside [2]. The record is a trial description; it does not report outcomes.

Nicotinamide riboside and pterostilbene in amyotrophic lateral sclerosis

Two registered trial records describe a combination of nicotinamide riboside (NR) and pterostilbene in amyotrophic lateral sclerosis. Both state that research from the investigators' department showed increased activity in histone deacetylation enzymes (sirtuins), together with increased access to NAD, can delay disease progression; NR is described as a means of increasing cellular access to NAD and pterostilbene as a sirtuin stimulator. The stated aim is to study whether the combination can inhibit neurodegeneration in ALS [4][5]. The population described is people with ALS. These are trial records, not reports of results.

Nicotinamide riboside and pterostilbene in muscle regeneration in elderly humans

A registered trial record states that successful skeletal muscle regeneration depends on a functional pool of muscle stem cells, termed satellite cells, which remain quiescent in adulthood and undergo proliferation and self-renewal in response to muscle damage. It notes that during aging there is a loss of satellite cell quiescence and that satellite cells more readily enter an ageing state that impairs their function. The record states that animal studies have revealed a common denominator for increasing satellite cell function and activity, namely sirtuin activation, and that natural stimulators of sirtuins include nicotinamide riboside, an NAD+ precursor, and the polyphenol pterostilbene. The study described aims to investigate this in elderly humans [6]. The animal-only portion of that rationale is stated as such in the source.

Comparison of the registered sirtuin-related trial records

Sirtuins within nutrient-sensing networks in adult stem cells

A review of nutrient-sensing pathways reports that mTOR, AMPK, sirtuins and insulin/IGF-1 signalling act as central regulators of adult stem cell fate by dynamically modulating cellular metabolism, and proposes a framework integrating these pathways into a network that dictates metabolic transitions [7]. This is a review-level synthesis rather than a study in a named population.

NAD+ availability and sirtuin-linked enzymes in cardiovascular research

A review of nicotinamide adenine dinucleotide in cardiovascular disease describes NAD+ as an important redox cofactor with a major role in energy metabolism, and surveys current understanding of NAD+ in cardiovascular disease, including activation of the rate-limiting enzyme nicotinamide phosphoribosyltransferase [8]. Sirtuins are NAD+-dependent, so this literature is relevant to their biology, but the review is not a sirtuin intervention study.

Sirtuins in ovarian aging research

A review of aging and longevity mechanisms reports that ovarian aging is characterised by progressive follicular reserve depletion, mitochondrial dysfunction, oxidative stress and endocrine decline, and examines molecular mechanisms driving ovarian aging alongside emerging strategies to preserve reproductive longevity [9]. Sirtuins appear within this mechanistic literature as part of the broader aging framework rather than as the subject of a reported trial.

Where the evidence sits

• Review-level and target-mapping material: references [1], [7], [8] and [9].
• Registered trial descriptions without reported outcomes: references [2], [4], [5] and [6].
• Animal-only rationale, stated as such by the source: the satellite cell and sirtuin activation findings cited in [6].
• No in vitro findings are reported in the evidence supplied for this page.

If you are reading this for personal health reasons

The materials described on this page are supplied for laboratory research use only. We do not provide dosing information, medical guidance or recommendations for personal use of any compound. Anyone considering a compound for themselves should speak to a licensed clinician.

Sources

• [1] Molecular Targets in Modern Cosmetic Science — https://europepmc.org/article/PMC/PMC13567315
• [2] Sirtuin Activators and Weight Loss — https://clinicaltrials.gov/study/NCT07802548
• [3] Mitochondrial-Derived Peptides as Therapeutics and Biomarkers for Combating Vascular Aging and Associated Cardiovascular Diseases — https://europepmc.org/article/PMC/PMC12951053
• [4] A Trial of Nicotinamide/Pterostilbene Supplement in ALS: The NO-ALS Extension Study — https://clinicaltrials.gov/study/NCT05095571
• [5] The NO-ALS Study: A Trial of Nicotinamide/Pterostilbene Supplement in ALS — https://clinicaltrials.gov/study/NCT04562831
• [6] Effect of Nicotinamide Riboside and Pterostilbene Supplementation on Muscle Regeneration in Elderly Humans — https://clinicaltrials.gov/study/NCT03754842
• [7] Nutrient-sensing pathways in adult stem cells: Orchestrating homeostasis, aging, and disease — https://pubmed.ncbi.nlm.nih.gov/42546460/
• [8] Role of nicotinamide adenine dinucleotide in cardiovascular disease — https://pubmed.ncbi.nlm.nih.gov/42047243/
• [9] Mechanistic insights into aging and longevity: Implications for ovarian function and health — https://pubmed.ncbi.nlm.nih.gov/41833148/