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Natural Bioactive Molecules for the Management of Age-Related Disorders

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 September 2024 | Viewed by 13339

Special Issue Editors

Special Issue Information

Dear Colleagues,

Over recent years, there has been a growing demand for wellbeing, improved physical appearance and healthy longevity in a large part of the world population. Cellular aging implicates alterations of several physiological mechanisms that ultimately lead to the functional decline of the organism. The major age-related disorders are not only limited to pathological conditions, including vascular inflammation and cardiovascular, neurodegenerative, rheumatic, and neuropathic diseases, but also all physical (aesthetic) alterations, such as skin wrinkles, skin spots, and hair loss.

Natural compounds have been primary resources for human disease treatment and for the preservation of a good human health state. In this scenario, there is growing interest in identifying natural molecules with potential biological effects in ameliorating or preventing age-related disorders.

In this Special Issue, we invite researchers to provide original research articles, clinical reports, and review articles related to every type of natural compound for the management of age-related disorders. We are pleased to invite articles from researchers in a wide range of fields, such as food chemistry, cosmetics, pharmacology, medicine, nutrition, and biochemistry. Our goal is to make this Special Issue a valuable collection of new knowledge in this field.

Prof. Dr. Gian Carlo Tenore
Dr. Maria Maisto
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • natural bioactive compound
  • oxidative stress
  • metabolic syndrome
  • anti-aging molecules
  • aging-related disorders
  • well-being
  • good-looking

Published Papers (6 papers)

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Research

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20 pages, 2647 KiB  
Article
NAD-Driven Sirtuin Activation by Cordyceps sinensis Extract: Exploring the Adaptogenic Potential to Promote Skin Longevity
by Ritamaria Di Lorenzo, Danila Falanga, Lucia Ricci, Antonio Colantuono, Giovanni Greco, Maura Angelillo, Fiorella Nugnes, Teresa Di Serio, Dorothea Costa, Annalisa Tito and Sonia Laneri
Int. J. Mol. Sci. 2024, 25(8), 4282; https://doi.org/10.3390/ijms25084282 - 12 Apr 2024
Viewed by 1144
Abstract
In recent years, there has been increasing interest in utilizing Traditional Chinese Medicine principles and natural bioactive compounds to combat age-related ailments and enhance longevity. A Cordyceps sinensis mycelium hydroethanolic extract (CsEx), which was standardized in cordycepin and adenosine using UHPLC-DAD, was investigated [...] Read more.
In recent years, there has been increasing interest in utilizing Traditional Chinese Medicine principles and natural bioactive compounds to combat age-related ailments and enhance longevity. A Cordyceps sinensis mycelium hydroethanolic extract (CsEx), which was standardized in cordycepin and adenosine using UHPLC-DAD, was investigated for its adaptogenic properties using in vitro assays and a double-blind, placebo-controlled clinical trial involving 40 subjects. The CsEx demonstrated activity at a concentration of 0.0006%, significantly increasing sirtuin expression (SirT1: +33%, SirT3: +10%, SirT6: +72%, vs. CTR, p < 0.05) and NAD+ synthesis in HaCat cells (+20% vs. CTR, p < 0.001). Moreover, the CsEx boosted ATP production by 68% in skin cells, correlating with higher skin energy values (+52.0% at D28, p < 0.01) in the clinical trial. Additionally, CsEx notably reduced cytosolic reactive oxygen species (ROS) by 30% in HaCaT cells (p < 0.05) and enhanced collagen production both in vitro (+69% vs. CTR, p < 0.01) and in vivo (+10% vs. D0, p < 0.01), confirmed by ultrasound examination. Furthermore, CsEx’s stimulation of fibroblasts, coupled with its antioxidant and energizing properties, led to a significant reduction in wrinkles by 28.0% (D28, p < 0.001). This study underscores Cordyceps sinensis hydroethanolic extract’s potential in regulating skin cell energy metabolism and positively influencing the mechanisms associated with skin longevity control. Full article
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17 pages, 3957 KiB  
Article
Annurca Apple Oleolite as Functional Ingredient for the Formulation of Cosmetics with Skin-Antiaging Activity
by Ritamaria Di Lorenzo, Maria Maisto, Lucia Ricci, Vincenzo Piccolo, Adua Marzocchi, Giovanni Greco, Gian Carlo Tenore and Sonia Laneri
Int. J. Mol. Sci. 2024, 25(3), 1677; https://doi.org/10.3390/ijms25031677 - 30 Jan 2024
Cited by 2 | Viewed by 1108
Abstract
The identification of natural remedies for the management of the skin aging process is an increasingly growing issue. In this context, ursolic acid (UA), a ubiquitous molecule, mainly contained in Annurca apple (AA) fruit, has demonstrated valuable cosmetic potential. To this end, in [...] Read more.
The identification of natural remedies for the management of the skin aging process is an increasingly growing issue. In this context, ursolic acid (UA), a ubiquitous molecule, mainly contained in Annurca apple (AA) fruit, has demonstrated valuable cosmetic potential. To this end, in the current study, the AA oleolite (AAO, extract in sunflower oil containing 784.40 ± 7.579 µg/mL of UA) was evaluated to inhibit porcine elastase enzymatic reactions through a validated spectrophotometric method. AAO has shown a valuable capacity to contrast the elastase enzyme with a calculated IC50 of 212.76 mg/mL, in comparison to UA (IC50 of 135.24 μg/mL) pure molecules and quercetin (IC50 of 72.47 μg/mL) which are used as positive controls. In this context and in view of the valuable antioxidant potential of AAO, its topical formulation with 2.5% (w/w) AAO was tested in a placebo-controlled, double-blind, two-arm clinical study on 40 volunteers. Our results indicated that after 28 days of treatment, a significant reduction of the nasolabial fold (−7.2 vs. baseline T0, p < 0.001) and forehead wrinkles (−5.3 vs. baseline T0, p < 0.001) were registered in combination with a valuable improvement of the viscoelastic skin parameters, where skin pliability/firmness (R0) and gross elasticity (R2) were significantly ameliorated (−13% vs. baseline T0, p < 0.001 for R0 and +12% vs. baseline T0, p < 0.001 for R2). Finally, considering the positive correlation between skin elasticity and hydration, the skin moisture was evaluated through the estimation of Trans epidermal water loss (TEWL) and skin conductance. Full article
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16 pages, 2979 KiB  
Article
The Effect of Adjuvant Therapy with Molecular Hydrogen on Endogenous Coenzyme Q10 Levels and Platelet Mitochondrial Bioenergetics in Patients with Non-Alcoholic Fatty Liver Disease
by Zuzana Sumbalová, Jarmila Kucharská, Zuzana Rausová, Anna Gvozdjáková, Mária Szántová, Branislav Kura, Viliam Mojto and Ján Slezák
Int. J. Mol. Sci. 2023, 24(15), 12477; https://doi.org/10.3390/ijms241512477 - 5 Aug 2023
Cited by 5 | Viewed by 2254
Abstract
Molecular hydrogen (H2) has been recognized as a novel medical gas with antioxidant and anti-inflammatory effects. Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increased fat accumulation in liver tissue caused by factors other than alcohol consumption. Platelet mitochondrial [...] Read more.
Molecular hydrogen (H2) has been recognized as a novel medical gas with antioxidant and anti-inflammatory effects. Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increased fat accumulation in liver tissue caused by factors other than alcohol consumption. Platelet mitochondrial function is considered to reflect systemic mitochondrial health. We studied the effect of adjuvant therapy with hydrogen-rich water (HRW) on coenzyme Q10 (CoQ10) content and platelet mitochondrial bioenergetics in patients with NAFLD. A total of 30 patients with NAFLD and 15 healthy volunteers were included in this clinical trial. A total of 17 patients (H2 group) drank water three × 330 mL/day with tablets producing HRW (>4 mg/L H2) for 8 weeks, and 13 patients (P group) drank water with placebo tablets producing CO2. The concentration of CoQ10-TOTAL was determined by the HPLC method, the parameter of oxidative stress, thiobarbituric acid reactive substances (TBARS), by the spectrophotometric method, and mitochondrial bioenergetics in platelets isolated from whole blood by high-resolution respirometry. The patients with NAFLD had lower concentrations of CoQ10-TOTAL in the blood, plasma, and platelets vs. the control group. Mitochondrial CI-linked LEAK respiration was higher, and CI-linked oxidative phosphorylation (OXPHOS) and CII-linked electron transfer (ET) capacities were lower vs. the control group. Plasma TBARS concentrations were higher in the H2 group. After 8 weeks of adjuvant therapy with HRW, the concentration of CoQ10 in platelets increased, plasma TBARS decreased, and the efficiency of OXPHOS improved, while in the P group, the changes were non-significant. Long-term supplementation with HRW could be a promising strategy for the acceleration of health recovery in patients with NAFLD. The application of H2 appears to be a new treatment strategy for targeted therapy of mitochondrial disorders. Additional and longer-term studies are needed to confirm and elucidate the exact mechanisms of the mitochondria-targeted effects of H2 therapy in patients with NAFLD. Full article
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19 pages, 2440 KiB  
Article
Dietary Walnuts Preserve Aspects of Health Span and Alter the Hippocampal Lipidome in Aged High-Fat Diet-Fed Mice
by Ardijana Novaj, Matthew G. Engel, Ruixuan Wang, Kai Mao, Xiaonan Xue, Yam Amir, Gil Atzmon and Derek M. Huffman
Int. J. Mol. Sci. 2023, 24(3), 2314; https://doi.org/10.3390/ijms24032314 - 24 Jan 2023
Viewed by 2392
Abstract
Evidence continues to accrue that aging and its diseases can be delayed by pharmacologic and dietary strategies that target the underlying hallmarks of the aging process. However, identifying simple, safe, and effective dietary strategies involving the incorporation of whole foods that may confer [...] Read more.
Evidence continues to accrue that aging and its diseases can be delayed by pharmacologic and dietary strategies that target the underlying hallmarks of the aging process. However, identifying simple, safe, and effective dietary strategies involving the incorporation of whole foods that may confer some protection against the aging process is also needed. Recent observational studies have suggested that nut consumption can reduce mortality risk in humans. Among these, walnuts are particularly intriguing, given their high content of n-3 fatty acids, fiber, and antioxidant and anti-inflammatory compounds. To this end, 12-month-old male CB6F1 mice were provided either a defined control low-fat diet (LFD), a control high-fat diet (HFD), or an isocaloric HFD containing 7.67% walnuts by weight (HFD + W), and measures of healthspan and related biochemical markers (n = 10–19 per group) as well as survival (n = 20 per group) were monitored. Mice provided the HFD or HFD + W demonstrated marked weight gain, but walnuts lowered baseline glucose (p < 0.05) and tended to temper the effects of HFD on liver weight gain (p < 0.05) and insulin tolerance (p = 0.1). Additional assays suggested a beneficial effect on some indicators of health with walnut supplementation, including preservation of exercise capacity and improved short-term working memory, as determined by Y maze (p = 0.02). However, no effect was observed via any diet on inflammatory markers, antioxidant capacity, or survival (p = 0.2). Ingenuity Pathway Analysis of the hippocampal transcriptome identified two processes predicted to be affected by walnuts and potentially linked to cognitive function, including estrogen signaling and lipid metabolism, with changes in the latter confirmed by lipidomic analysis. In summary, while walnuts did not significantly improve survival on a HFD, they tended to preserve features of healthspan in the context of a metabolic stressor with aging. Full article
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Review

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21 pages, 682 KiB  
Review
Clinical Studies Using Topical Melatonin
by Giovanni Greco, Ritamaria Di Lorenzo, Lucia Ricci, Teresa Di Serio, Eleonora Vardaro and Sonia Laneri
Int. J. Mol. Sci. 2024, 25(10), 5167; https://doi.org/10.3390/ijms25105167 - 9 May 2024
Viewed by 903
Abstract
Melatonin is ubiquitously present in all animals and plants, where it exerts a variety of physiological activities thanks to its antioxidant properties and its key role as the first messenger of extracellular signaling functions. Most of the clinical studies on melatonin refer to [...] Read more.
Melatonin is ubiquitously present in all animals and plants, where it exerts a variety of physiological activities thanks to its antioxidant properties and its key role as the first messenger of extracellular signaling functions. Most of the clinical studies on melatonin refer to its widespread oral use as a dietary supplement to improve sleep. A far smaller number of articles describe the clinical applications of topical melatonin to treat or prevent skin disorders by exploiting its antioxidant and anti-inflammatory activities. This review focuses on the clinical studies in which melatonin was applied on the skin as a photoprotective, anti-aging, or hair growth-promoting agent. The methodologies and results of such studies are discussed to provide an overall picture of the state of the art in this intriguing field of research. The clinical studies in which melatonin was applied on the skin before exposure to radiation (UV, sunlight, and high-energy beams) were all characterized by an appropriate design (randomized, double-blind, and placebo-controlled) and strongly support its clinical efficacy in preventing or reducing skin damage such as dermatitis, erythema, and sunburn. Most of the studies examined in this review do not provide a clear demonstration of the efficacy of topical melatonin as a skin anti-aging or as a hair growth-promoting agent owing to limitations in their design and/or to the use of melatonin combined with extra active ingredients, except for one trial that suggests a possible beneficial role of melatonin in treating some forms of alopecia in women. Further research efforts are required to reach definitive conclusions concerning the actual benefits of topical melatonin to counteract skin aging and hair loss. Full article
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27 pages, 6474 KiB  
Review
Vascular Ageing: Mechanisms, Risk Factors, and Treatment Strategies
by Jingyuan Ya and Ulvi Bayraktutan
Int. J. Mol. Sci. 2023, 24(14), 11538; https://doi.org/10.3390/ijms241411538 - 16 Jul 2023
Cited by 6 | Viewed by 4597
Abstract
Ageing constitutes the biggest risk factor for poor health and adversely affects the integrity and function of all the cells, tissues, and organs in the human body. Vascular ageing, characterised by vascular stiffness, endothelial dysfunction, increased oxidative stress, chronic low-grade inflammation, and early-stage [...] Read more.
Ageing constitutes the biggest risk factor for poor health and adversely affects the integrity and function of all the cells, tissues, and organs in the human body. Vascular ageing, characterised by vascular stiffness, endothelial dysfunction, increased oxidative stress, chronic low-grade inflammation, and early-stage atherosclerosis, may trigger or exacerbate the development of age-related vascular diseases, which each year contribute to more than 3.8 million deaths in Europe alone and necessitate a better understanding of the mechanisms involved. To this end, a large number of recent preclinical and clinical studies have focused on the exponential accumulation of senescent cells in the vascular system and paid particular attention to the specific roles of senescence-associated secretory phenotype, proteostasis dysfunction, age-mediated modulation of certain microRNA (miRNAs), and the contribution of other major vascular risk factors, notably diabetes, hypertension, or smoking, to vascular ageing in the elderly. The data generated paved the way for the development of various senotherapeutic interventions, ranging from the application of synthetic or natural senolytics and senomorphics to attempt to modify lifestyle, control diet, and restrict calorie intake. However, specific guidelines, considering the severity and characteristics of vascular ageing, need to be established before widespread use of these agents. This review briefly discusses the molecular and cellular mechanisms of vascular ageing and summarises the efficacy of widely studied senotherapeutics in the context of vascular ageing. Full article
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