de Afonso Bonotto NC, Musachio E, Felin GD
… +4 more, Felin GD, Schwanke CHA, da Cruz IBM, Barbisan F
Oxid Med Cell Longev
· 2026 · PMID 42133650
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This narrative review discusses the relationship between structural changes in the skin and mitochondrial function during aging and evaluates emerging therapeutic interventions targeting mitochondrial dysfunction. An ana...This narrative review discusses the relationship between structural changes in the skin and mitochondrial function during aging and evaluates emerging therapeutic interventions targeting mitochondrial dysfunction. An analysis of 49 scientific articles published between 2015 and 2025 was conducted using descriptors including "skin aging," "mitochondrial dysfunction," "oxidative stress," and "cutaneous senescence," and articles were retrieved from PubMed, Scopus, and ScienceDirect. Additional research was conducted using terms related to therapeutic interventions, including "mitochondrial therapies AND skin aging OR cutaneous aging." Original research articles were included based on thematic relevance, recency, and scientific rigor. The reviewed studies suggest that oxidative stress, mainly from mitochondrial metabolism, is a primary cause of skin cell senescence. Mitochondrial dysfunction emerges as a central mechanistic hub linking oxidative stress, mitochondrial genome instability, chronic low-grade inflammation (inflammaging), and the senescence-associated secretory phenotype (SASP) to age-related structural and functional skin alterations. Mitochondria maintain skin homeostasis through cell proliferation, differentiation, and genetic material synthesis. With advancing age, mitochondrial DNA copy number declines significantly, while reactive oxygen species production increases, thereby compromising cellular energy metabolism. Emerging mitochondrial-targeted therapeutic strategies, including nicotinamide adenine dinucleotide (NAD) precursors, coenzyme Q10 supplementation, senolytics, and modulators of mitochondrial quality control, show promising effects on skin aging parameters in preclinical and early clinical studies. However, current evidence is based on small clinical trials with short follow-up periods, and long-term safety data remain limited. Therefore, while mitochondria are not the sole source of oxidants, growing evidence indicates that oxidative stress-driven mitochondrial dysfunction represents a priority pathogenic mechanism in skin aging. The clinical translation of mitochondrial-targeted therapies represents an innovative opportunity for anti-aging strategies, although the validation of standardized biomarkers and longitudinal safety investigations remains critical for clinical implementation.
Chobsuay N, Chonpathompikunlert P, Srivilai J
… +4 more, Malakul W, Limpeanchob N, Aimjongjun S, Tunsophon S
Oxid Med Cell Longev
· 2026 · PMID 42083443
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High-fat diets (HFDs) are a key contributor to obesity and promote oxidative stress and inflammation, which are associated with muscle atrophy and insulin resistance (IR). Passiflora edulis exhibits anti-obesity, antioxi...High-fat diets (HFDs) are a key contributor to obesity and promote oxidative stress and inflammation, which are associated with muscle atrophy and insulin resistance (IR). Passiflora edulis exhibits anti-obesity, antioxidant, and anti-inflammatory effects. The study aimed to investigate the potential benefit of P. edulis f. flavicarpa (PF) extract in preventing obesity-associated muscle atrophy and IR. The PF extract effectively inhibited cholesterol micelle solubility with an IC of 3431 µg/mL and decreased fat accumulation in 3T3-L1 adipocytes. Furthermore, this study investigated a model of HFD-induced IR and muscle atrophy in rats. Thirty-five male Sprague-Dawley (SD) rats were induced with obesity by HFD and were administered 250 and 500 mg/kg/day of PF extract. Rats fed with an HFD were associated with fat accumulation and oxidative stress, which promoted inflammation, muscle damage, muscle atrophy, and IR in obese rats. However, administration of PF extract effectively mitigated these effects. The PF extract decreased fat accumulation in white adipose tissues and gastrocnemius (GAS) muscle by inhibiting fat absorption and synthesis, particularly Cd36 and Hmgcr. The PF extract also notably reduced oxidative stress-induced muscle inflammation and damage via elevating nuclear factor erythroid 2-related factor 2 (Nrf2) and reducing nuclear factor kappa B (NF-κB) expressions. Additionally, PF extract was found to mechanistically prevent muscle atrophy by inhibiting Fbxo32, Trim63, and B-cell lymphoma 2 (BCL2)-associated X (Bax) expressions, while enhancing Bcl2 expression. We also found that PF extract mitigated muscle IR by upregulation of the insulin receptor substrate-1/phosphatidylinositol-3 kinase/protein kinase B (IRS-1/PI3K/AKT) pathway and Slc2a4 expression. The findings indicate that PF extract can prevent skeletal muscle loss and IR in obesity by modulating oxidative stress, inflammation, and activating IRS-1/PI3K/AKT signaling pathway.
Jiang X, Jiang T, Pan Z
… +4 more, Chen C, Ji X, Wang X, Zong W
Oxid Med Cell Longev
· 2026 · PMID 42057475
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PURPOSE: This study aimed to investigate the effect of ginsenoside Rb1 (Gs-Rb1) on endothelial cell (EC) pyroptosis in atherosclerosis (AS). METHOD: ApoE mice and mouse aortic endothelial cells (MAECs) were used as resea...PURPOSE: This study aimed to investigate the effect of ginsenoside Rb1 (Gs-Rb1) on endothelial cell (EC) pyroptosis in atherosclerosis (AS). METHOD: ApoE mice and mouse aortic endothelial cells (MAECs) were used as research subjects. An in vivo AS model was established by feeding ApoE mice a high-fat diet (HFD) for 3 months, followed by intragastric administration of Gs-Rb1 at 40 mg/kg/day for 3 months. Pathological changes were evaluated by hematoxylin-eosin (HE) and Oil Red O staining. Caspase-1 expression was detected by immunofluorescence. Pyroptosis-related protein and mRNA levels were measured by Western blotting and RT-PCR. Inflammatory factors (IL-18 and IL-1β) and LDH were quantified by ELISA. For in vitro experiments, MAECs were stimulated with oxidized low-density lipoprotein (ox-LDL, 150 μg/mL) to induce pyroptosis, followed by treatment with Gs-Rb1 (60 or 80 μg/mL) for 12 h. Cell death was assessed by flow cytometry. RESULT: Gs-Rb1 significantly reduced aortic plaque area in mice. It decreased the expression of pyroptosis-related proteins (caspase-1, cleaved caspase-1, GSDMD, and NLRP3) and mRNA levels in aortic tissues. Serum levels of LDH, IL-18, and IL-1β were also significantly reduced. In vitro, Gs-Rb1 reduced cell death rate and inhibited pyroptosis in endothelial cells (ECs). CONCLUSION: This study confirms the therapeutic effect of Gs-Rb1 on AS at both animal and cellular levels. Inhibition of EC pyroptosis may be the key mechanism underlying the anti-atherosclerotic effects of Gs-Rb1.
Zia B, Alshehhi MHA, Sheikh A
… +3 more, Mirza S, Subramanya SB, Ojha SK
Oxid Med Cell Longev
· 2026 · PMID 41952468
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Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent for treating various malignancies, autoimmune diseases (AIDs), and inflammatory disorders. Despite its therapeutic efficacy, long term or h...Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent for treating various malignancies, autoimmune diseases (AIDs), and inflammatory disorders. Despite its therapeutic efficacy, long term or high-dose MTX treatment is associated with a significant risk of hepatotoxicity, leading to MTX-induced liver injury (MTX-LI). The pathogenesis of MTX-LI involves multiple mechanisms, including oxidative stress, mitochondrial dysfunction, inflammation, and altered metabolic processes, which collectively contribute to hepatocellular damage and fibrosis. Clinically, MTX-LI manifests as elevated liver enzymes, hepatic steatosis, and, in severe cases, cirrhosis, posing a challenge to treatment regimens. To mitigate MTX-LI, a growing body of research has focused on exploring therapeutic and/or preventive potential and pharmacological mechanisms of phytochemicals and pharmaceuticals. Phytochemicals, including flavonoids, terpenoids, alkaloids, and polyphenols, exhibit hepatoprotective effects attributed to their antioxidant, anti-inflammatory, and antiapoptotic properties that can counteract MTX-induced hepatic damage. Additionally, various pharmaceutical agents possessing antioxidants and anti-inflammatory properties and favorably modulate metabolic pathways have shown promise in reducing the severity or progression of of MTX-LI. The phytochemicals or pharmaceuticals showed beneficial in MTX-LI primarily act by scavenging reactive oxygen species (ROS), modulating inflammatory pathways, and improving liver regeneration. Integrated together, its apparent that naturally occurring many phytochemicals as well as synthetic agents of pharmaceutical relevance are capable of preventing or alleviating MTX-LI. However, the optimal strategies for integrating these agents into clinical practice require further investigations to highlight safety and efficacy in humans followed by pharmacological rationale of their possible use in therapeutics. Future directions should focus on elucidating the precise molecular mechanisms, establish safety and efficacy in humans, conducting regulatory toxicology studies and randomized clinical trials, and developing combination therapies for promotion as protective agents or adjuvants to maximize efficacy and minimize adverse effects.