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Open research questions in Sirtuins and Resveratrol in Medicine

411 gap statements mined from Sirtuins and Resveratrol in Medicine papers in our 7.9M-paper local library, which holds 1,268 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Further studies are needed to fully elucidate the mechanisms by which the C/EBPβ/AEP pathway contributes to vascular deterioration and systemic aging. Investigations into the therapeutic potential of targeting the C/EBPβ/AEP pathway in humans are warranted. Research into the role of other pathways and factors in mediating aging-related pathologies is necessary.

    Endothelial C/EBPβ/AEP pathway drives vascular deterioration and systemic aging · 2026 · DOI

  • The underlying molecular mechanisms driving vascular deterioration remain poorly understood. The role of the C/EBPβ/AEP pathway in vascular aging and systemic frailty is not well understood. There is a need for therapeutic strategies to preserve vascular integrity and mitigate systemic frailty in aging populations.

    Endothelial C/EBPβ/AEP pathway drives vascular deterioration and systemic aging · 2026 · DOI

  • One of the challenges is the limited therapeutic index of phenytoin, making it easy to reach toxic levels. Another challenge is the need to evaluate cerebellar functions and morphology in rats treated with phenytoin and dapagliflozin. The study also faces the challenge of investigating the role of the SIRT1/Nrf2/HO-1 pathway in the protective effect of dapagliflozin.

    Protective effect of dapagliflozin against phenytoin-induced cerebellar dysfunction and histological alterations in rats: the role of SIRT1/Nrf2/HO-1 pathway · 2026 · DOI

  • There is a need to investigate the protective role of dapagliflozin against phenytoin-induced cerebellar dysfunction in rats. The current study aims to fill this gap by evaluating cerebellar functions and morphology in rats treated with phenytoin and dapagliflozin.

    Protective effect of dapagliflozin against phenytoin-induced cerebellar dysfunction and histological alterations in rats: the role of SIRT1/Nrf2/HO-1 pathway · 2026 · DOI

  • The complexity of prostate cancer progression and the need for a better understanding of the underlying mechanisms. The challenge of developing effective therapeutic strategies for metastatic prostate cancer.

    Molecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression · 2024 · DOI

  • The study did not investigate the in vivo efficacy of the ASDs. The study used a limited number of polymers (PVP K30 and VA64) and did not explore other potential polymers. The study did not evaluate the long-term stability of the ASDs.

    Enhanced Antioxidant and Neuroprotective Properties of Pterostilbene (Resveratrol Derivative) in Amorphous Solid Dispersions · 2024 · DOI

  • It highlights the need for further research on the effects of resveratrol on age-related infertility, polycystic ovary syndrome, and endometriosis.

    Molecular Mechanism of Resveratrol and Its Therapeutic Potential on Female Infertility · 2024 · DOI

  • Nanoformulations may improve exposure, but depression specific clinical validation is lacking.

    Resveratrol in depression: mechanistic networks, preclinical evidence and translational perspectives · 2026 · DOI

  • Sex influences early-life immunity and infection outcomes, yet how metabolic mechanisms regulate these effects remain unclear.

    NAD metabolism mediates a sex-specific protection against early life infections · 2026 · DOI

  • SIRT7 is linked to cancer, yet its function in gastric cancer (GC) remains unclear.

    SIRT7 Mediated‐PTEN Desuccinylation Drives Gastric Tumorigenesis by Activating PI3K/AKT Pathway · 2026 · DOI

  • Despite the understanding of these outcomes, it remains unclear how glucocorticoid excess affects the metabolically critical nicotinamide adenine dinucleotide (NAD+) and related metabolites and transcripts, including redox cofactors, intermediates and biosynthetic enzymes.

    Glucocorticoid excess disrupts NAD+ homeostasis in male and female mice · 2026 · DOI

  • There is limited information, however, about the biosynthetic pathways that replenish intracellular NAD+, which is continuously turned over in undifferentiated mouse embryonic stem cells.

    Nicotinamide salvage is required for proliferation and sustaining self-renewal in undifferentiated embryonic stem cells · 2025 · DOI

  • Knee osteoarthritis (OA) and frailty share pathophysiological processes and are leading causes of disability in the geriatric population; however, effective interventions remain elusive.

    Resveratrol treatment increases sirtuin 1 levels and alleviates frailty phenotype in knee osteoarthritis patients: a randomised placebo-controlled clinical trial · 2025 · DOI

  • Myocyte enhancer factor 2A (MEF2A), a transcription factor implicated in coronary artery disease, remains unexplored in vascular redox regulation.

    Myocyte enhancer factor 2A orchestrates vascular redox homeostasis via direct transcriptional activation of SIRT1 · 2025 · DOI

  • In HCC samples, NAD-dependent deacetylase sirtuin 2 (SIRT2) levels are increased and associated with a significantly worse prognosis, but the role of SIRT2 in hepatocarcinogenesis remains controversial.

    Suppression of Hepatocellular Carcinoma by Deletion of SIRT2 in Hepatocytes via Elevated C/EBPβ/GADD45γ · 2025 · DOI

  • Whether Nicotinamide adenine dinucleotide supplementation may be beneficial for delirium has not been explored yet.

    Acute Nicotinamide Adenine Dinucleotide Supplementation via Nicotinamide Mononucleotide Does Not Rescue Functional Impairment in a Lipopolysaccharide-induced Delirium Mouse Model · 2025 · DOI

  • The relationship between SIC and protein acetylation, particularly the balance between acetylation and deacetylation in cardiomyocyte subcellular structures, as well as how nuclear–mitochondrial coordination maintains standard antioxidant stress capacity, remains unclear.

    SIRT3-FOXO3a Isoforms Forge Nuclear–Mitochondrial Links to Combat Sepsis-Induced Cardiomyopathy Oxidative Stress in Mice · 2025 · DOI

  • The largest gap is long-term safety, as NAD biology intersects with DNA repair, immune surveillance, inflammation, and cellular proliferation. There is no evidence that NAD boosters cause cancer, but it is equally improper to assume long-term safety without outcomes-based trials.

    NAD⁺ Injections and NAD Boosters: Evidence Gaps, Safety Concerns, and Public Health Implications · 2026 · DOI

  • The need for a safer alternative to mitigate MP-induced hepatotoxicity. The lack of understanding of the potential health concerns of MP exposure.

    Mitigating methylparaben hepatotoxicity: Resveratrol’s role in oxidative stress, inflammation, and apoptotic modulation · 2026 · DOI

  • Further research employing oral administration at clinically relevant doses, alongside pharmacokinetic evaluations and larger sample sizes, is essential to confirm these findings and advance the clinical translation of RES.

    Mitigating methylparaben hepatotoxicity: Resveratrol’s role in oxidative stress, inflammation, and apoptotic modulation · 2026 · DOI

  • While promising results have been observed in animal studies and some human trials, the overall evidence is mixed.

    Effects of resveratrol supplementation on inflammatory markers, fatigue scale, fasting blood sugar and lipid profile in relapsing-remitting multiple sclerosis patients: a double-blind, randomized placebo-controlled trial · 2024 · DOI

  • This paper is a narrative synthesis and does not constitute a systematic review or meta-analysis. The clinical evidence base is evolving, and future long-duration trials may change benefit–risk assessments. Specific regulatory details vary by jurisdiction; this analysis emphasises internationally relevant public health principles and widely cited regulatory evidence.

    NAD⁺ Injections and NAD Boosters: Evidence Gaps, Safety Concerns, and Public Health Implications · 2026 · DOI

  • Directed research into better treatment options with resveratrol, - Investigation of the therapeutic potential of halogenated RSV derivatives, - Exploration of the use of nanoparticles to enhance the bioavailability…

    Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It? · 2024 · DOI

  • Investigation of the in vivo efficacy of the ASDs. Exploration of other potential polymers for ASD preparation. Evaluation of the long-term stability of the ASDs. Investigation of the potential applications of ASDs in various diseases.

    Enhanced Antioxidant and Neuroprotective Properties of Pterostilbene (Resveratrol Derivative) in Amorphous Solid Dispersions · 2024 · DOI

  • Developing NAPRT inhibitors to be utilized together with NAMPT inhibitors against PH-activated tumors, - Investigating the potential of NMNAT inhibition in cancer therapy, - Exploring alternative NAD + -producing routes that could be relevant…

    Inhibitors of NAD+ Production in Cancer Treatment: State of the Art and Perspectives · 2024 · DOI

Most-cited papers in Sirtuins and Resveratrol in Medicine

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Open questions raised by papers listed on this page include: (1) Further studies are needed to fully elucidate the mechanisms by which the C/EBPβ/AEP pathway contributes to vascular deterioration and systemic aging (“Endothelial C/EBPβ/AEP pathway drives vascular deterioration and systemic aging”, 2026); (2) There is a need to investigate the protective role of dapagliflozin against phenytoin-induced cerebellar dysfunction in rats (“Protective effect of dapagliflozin against phenytoin-induced cerebellar…”, 2026); (3) Nanoformulations may improve exposure, but depression specific clinical validation is lacking (“Resveratrol in depression: mechanistic networks, preclinical evidence and…”, 2026); (4) Sex influences early-life immunity and infection outcomes, yet how metabolic mechanisms regulate these effects remain unclear (“NAD metabolism mediates a sex-specific protection against early life infections”, 2026); (5) SIRT7 is linked to cancer, yet its function in gastric cancer (GC) remains unclear (“SIRT7 Mediated‐PTEN Desuccinylation Drives Gastric Tumorigenesis by Activating…”, 2026). 411 gap statements have been mined from Sirtuins and Resveratrol in Medicine papers in our 7.9M-paper local library, which holds 1,268 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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