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Nutraceuticals and Healthy Aging: Molecular Mechanisms and Therapeutic Perspectives
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Nutraceuticals and Healthy Aging: Molecular Mechanisms and Therapeutic Perspectives

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: 20 August 2026 | Viewed by 5893

Special Issue Editor

Dr. Francesca Uberti

E-Mail Website
Guest Editor
Laboratory of Physiology, Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale, UPO, 13100 Vercelli, Italy
Interests: absorption mechanism; anti-inflammatory properties; antioxidant defence; bioavailability; brain ageing; cartilage inflammation; cell pain signalling; cognitive decline; food supplement; gut microbiome; gut-brain axis; high molecular weight hyaluronic acid; in vitro study; inflammatory bowel syndrome; intestinal absorption; mental disorder; natural extracts; nerve injury; neuropathic pain model; neuropathy; nutraceutical approach; oral absorption; oral probiotic formulation; oral supplementation; osteoarthritis; oxidative stress; peripheral neuraxis damage; physiology;probiotic; synergy effect; tissue degradation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Aging is a complex and multifactorial biological process associated with a progressive decline in physiological function and an increased risk of chronic diseases such as neurodegeneration, metabolic dysfunction, cardiovascular disease, skin aging, menopausal disorders, benign prostatic hyperplasia (BPH), and bone and joint diseases. In this context, interest in nutraceuticals, bioactive compounds with natural origin and with potential health benefits, has grown exponentially in recent years. This Special Issue aims to collect articles and reviews that explore the molecular mechanisms by which nutraceuticals can help promote healthy aging, delay the onset of age-related diseases, and improve quality of life in the elderly population. The goal is to provide an up-to-date, interdisciplinary overview of the role of nutraceuticals in healthy aging, integrating research from fields such as biochemistry, molecular biology, physiology, pharmacology, nutrition, and clinical medicine.

Dr. Francesca Uberti
Guest Editor

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Keywords

  • molecular mechanisms of the action of nutraceuticals on cellular aging
  • nutraceuticals and neuroprotection
  • effects of nutraceuticals on skin aging
  • nutraceuticals in the prevention or management of age-related metabolic diseases
  • interaction between nutraceuticals and gut microbiota in aging
  • nutraceuticals in bone and joint health
  • role of nutraceuticals in menopausal management
  • impact of nutraceuticals on BPH and prostate health
  • multi-target approaches of nutraceuticals in healthy aging
  • innovative nutraceutical delivery and formulation strategies to increase bioavailability
  • clinical and preclinical studies of nutraceuticals in the elderly population

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Published Papers (4 papers)

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Research

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20 pages, 2446 KB  
Article
Exploratory Effects of a Novel Nutraceutical on Senescence-Related Protein Biomarkers in Healthy Adults: A Pilot Proteomics Study
by Sarah A. Blomquist, Gregory Kelly, Christopher R. D’Adamo, Chang Han, Haleigh Parker, Sara Adães, Colin R. Gardner, Abhimanyu Ardagh, Shawn Ramer and William Scuba
Int. J. Mol. Sci. 2026, 27(10), 4406; https://doi.org/10.3390/ijms27104406 - 15 May 2026
Viewed by 353
Abstract
Cellular senescence drives aging and age-related disease through the accumulation of senescent cells and their senescence-associated secretory phenotype (SASP). Emerging evidence suggests intermittent (“hit-and-run”) senolytic interventions may improve healthspan by reducing senescent cell accumulation and the SASP. Healthy adults aged 45–79 were recruited [...] Read more.
Cellular senescence drives aging and age-related disease through the accumulation of senescent cells and their senescence-associated secretory phenotype (SASP). Emerging evidence suggests intermittent (“hit-and-run”) senolytic interventions may improve healthspan by reducing senescent cell accumulation and the SASP. Healthy adults aged 45–79 were recruited for a decentralized, single-arm pilot study (NCT06953518) evaluating 2 days of nutraceutical supplementation (Qualia Senolytic). Fingerstick blood samples and validated quality of life (QoL) questionnaire data were collected on days 0 and 7. Primary outcomes were SASP biomarkers measured by the Olink® Target 48 Cytokine panel, including tumor necrosis factor (TNF), interleukin-1 beta (IL-1β), interleukin-8 (CXCL8), and vascular endothelial growth factor A (VEGFA). Protein data were analyzed using linear mixed models and Wilcoxon signed-rank tests. Seventy-one adults enrolled and 53 (74.6%) provided paired protein samples. No significant changes occurred in primary outcomes. Exploratory unadjusted analyses revealed significant reductions in the established senescence chemokines CXCL9 and CXCL10, as well as CCL8 and CXCL11, and increases in interleukin-17F and oncostatin M. QoL significantly improved without safety concerns, though results are expectation-sensitive. Preliminary findings support the feasibility of this decentralized approach and identify candidate SASP biomarker signals in healthy adults warranting validation in randomized, placebo-controlled trials. Full article
(This article belongs to the Special Issue Nutraceuticals and Healthy Aging: Molecular Mechanisms and Therapeutic Perspectives)
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28 pages, 3173 KB  
Article
Combined Effects of Diosmin, Hesperidin, Ruscus aculeatus, Ananas comosus, and Bromelain on Endothelial Function and Gut Barrier Integrity In Vitro
by Rebecca Galla, Simone Mulè, Sara Ferrari, Claudio Molinari and Francesca Uberti
Int. J. Mol. Sci. 2025, 26(21), 10538; https://doi.org/10.3390/ijms262110538 - 29 Oct 2025
Cited by 1 | Viewed by 4163
Abstract
The endothelium, once considered merely a vascular lining responsible for selective permeability to water and electrolytes, is now recognised as a key regulator of vascular tone through the release of mediators such as oxylipins, nitric oxide, and hyperpolarizing factors. This in vitro study [...] Read more.
The endothelium, once considered merely a vascular lining responsible for selective permeability to water and electrolytes, is now recognised as a key regulator of vascular tone through the release of mediators such as oxylipins, nitric oxide, and hyperpolarizing factors. This in vitro study investigated the biological activity of Vesvein, a natural formulation containing Diosmin/Hesperidin, Ruscus aculeatus, Bromelain, and Ananas comosus, on intestinal and endothelial cells. Vesvein enhanced intestinal cell viability and preserved barrier integrity, as demonstrated by increased tight junction expression at both single and double concentrations. In endothelial cells, the compound improved parameters linked to venous insufficiency, elevating nitric oxide production by approximately 1.39-fold at a single dose and 1.65-fold at a double dose. These findings indicate a potential role for Vesvein in supporting endothelial health and vascular function in vitro. Preliminary evidence from intestinal models further suggests preserved barrier properties, which may positively influence absorption and bioavailability, thereby enhancing its vascular benefits. Full article
(This article belongs to the Special Issue Nutraceuticals and Healthy Aging: Molecular Mechanisms and Therapeutic Perspectives)
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Review

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28 pages, 2113 KB  
Review
Bat-Inspired Longevity: Immune Damage Management and Nutritional Modulation for Healthy Aging
by Sunmin Park and James W. Daily
Int. J. Mol. Sci. 2026, 27(10), 4467; https://doi.org/10.3390/ijms27104467 - 16 May 2026
Viewed by 123
Abstract
The exceptional longevity of bats challenges classical theories of inflammaging and suggests an alternative that improved resilience in responding to pathogens and cellular damage can increase longevity. Accordingly, we have developed the Core Longevity State Vector (CLSV-6) to characterize an expanded explanation for [...] Read more.
The exceptional longevity of bats challenges classical theories of inflammaging and suggests an alternative that improved resilience in responding to pathogens and cellular damage can increase longevity. Accordingly, we have developed the Core Longevity State Vector (CLSV-6) to characterize an expanded explanation for inflammaging that can be predictive of successful aging and used to develop potential strategies for successful aging. Despite high metabolic rates and persistent viral exposure, many bat species have much longer lifespans than would be predicted for mammals of their size. The increased longevity of many bat species is achieved through damage tolerance, regulated inflammasome activity, constitutive basal antiviral defenses, enhanced autophagy–mitophagy, and efficient resolution of inflammation, rather than through heightened inflammatory immunity. The CLSV-6 is introduced as a multidimensional immunotype framework integrating six conserved mechanisms that link bat immunity to bat longevity and to human healthy aging: (1) damage tolerance, (2) autophagy–mitophagy, (3) proteostasis (management of degraded proteins), (4) basal immune readiness without activation, (5) inflammasome regulation, and (6) inflammatory resolution capacity. Together, these mechanisms enable a robust antiviral defense when needed without chronic inflammation. Notably, centenarians converge toward this bat-like configuration. Studies suggest that centenarians often preserve more functional NK cells, better macrophage regulation, and improved anti-inflammatory control, with both bats and humans exhibiting reduced activation of the NLRP3 inflammasome, resulting in greater immune resilience. Building on this framework, functional foods—including polyphenols, fermented foods, and herbal extracts—are proposed as practical strategies to shift human immunity toward bat-like, CLSV-6 immunotype by enhancing cellular quality control, regulating inflammasome activity, strengthening basal antiviral readiness, and supporting inflammatory resolution, thereby redirecting longevity strategies from immune stimulation toward damage containment and repair. This review reframes longevity as an emergent property of integrated immune damage management and provides a mechanistic roadmap for nutritional interventions to engineer healthier human aging inspired by bat immunity. Full article
(This article belongs to the Special Issue Nutraceuticals and Healthy Aging: Molecular Mechanisms and Therapeutic Perspectives)
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25 pages, 399 KB  
Review
Exploring the Senotherapeutic Potential of Polyphenols in Aging and Disease: A Literature Review
by Luna Braučič Mitrovic and Khrystyna O. Semen
Int. J. Mol. Sci. 2026, 27(8), 3651; https://doi.org/10.3390/ijms27083651 - 19 Apr 2026
Viewed by 719
Abstract
Aging is associated with an increased risk of developing many age-related diseases (ARDs), which are of major global health concern. In recent years, cellular senescence, characterized by cell cycle arrest and development of a senescence-associated secretory phenotype (SASP), has emerged as a key [...] Read more.
Aging is associated with an increased risk of developing many age-related diseases (ARDs), which are of major global health concern. In recent years, cellular senescence, characterized by cell cycle arrest and development of a senescence-associated secretory phenotype (SASP), has emerged as a key mechanism of aging and ARDs and has been increasingly explored as a promising therapeutic target. Among dietary bioactive ingredients, fisetin and quercetin have gained attention because of their potential to act as senolytics and senomorphics. This narrative literature review summarizes existing evidence exploring the potential of fisetin and quercetin to modulate senescence and SASP biomarkers in animal models of aging and progeria, as well as in interventional studies involving human subjects with geriatric syndromes and/or various ARDs. It also provides a brief overview of the molecular mechanisms of senescence and attempts to identify potential drivers and barriers for the clinical translation of those nutrients. Full article
(This article belongs to the Special Issue Nutraceuticals and Healthy Aging: Molecular Mechanisms and Therapeutic Perspectives)
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