Pai KK, Shetye S, Patil R
… +4 more, Acharya S, Kulal KS, Patil A, Kamath SU
Oxid Med Cell Longev
· 2026 · PMID 42358203
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BACKGROUND: Nutrition is a key modifiable factor supporting mitochondrial health and is essential for ovarian function and women's health across the life course. From menarche to menopause, mitochondrial efficiency under...BACKGROUND: Nutrition is a key modifiable factor supporting mitochondrial health and is essential for ovarian function and women's health across the life course. From menarche to menopause, mitochondrial efficiency underpins physiological balance. The menopausal transition is particularly critical, as hormonal and neuroendocrine changes are associated with impaired mitochondrial function and increased risk of age-related disorders. AIM: This review aimed to systematically review and synthesize the available evidence on mitochondrial function across in vitro, animal, and human studies and to evaluate the potential protective role of vitamins and nutrients in maintaining mitochondrial health, with attention to sex-specific findings. METHODS: A systematic search was conducted across multiple electronic databases. Forty-six eligible studies were identified and critically reviewed for evidence on mitochondrial function, sex-based differences, and nutritional influences. RESULTS: Mitochondrial dysfunction may contribute to the pathophysiology of age-related disorders, including osteoporosis, cardiovascular disease, neurodegenerative conditions, and cancer. Nutritional factors are crucial for preserving mitochondrial integrity. Vitamins C, E, and D, NAD + precursors such as nicotinamide riboside, coenzyme Q10, MitoQ, fucoxanthin, and cabergoline reduce oxidative stress, enhance mitochondrial biogenesis, support electron transport chain activity and ATP production, and maintain redox balance. These actions promote mitochondrial resilience and cellular energy metabolism. Evidence further indicates that women, particularly during the menopausal transition, exhibit heightened vulnerability to mitochondrial dysfunction, highlighting the relevance of nutrition-based interventions. CONCLUSION: Optimizing dietary intake of vitamins, antioxidants, and mitochondrial cofactors is a cost-effective, accessible strategy to support mitochondrial health and reduce age-related disease risk in women.
Oxid Med Cell Longev
· 2026 · PMID 42298951
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Myofibroblasts are morphologically similar cells with diverse origins that exhibit characteristics of both fibroblasts and smooth muscle cells. Following insults, myofibroblasts play critical roles in tissue reintegratio...Myofibroblasts are morphologically similar cells with diverse origins that exhibit characteristics of both fibroblasts and smooth muscle cells. Following insults, myofibroblasts play critical roles in tissue reintegration and restitution. However, their prolonged presence and activity impede physiological recovery, leading to persistent or progressive tissue complications, as evidenced in corneal fibrosis and opacification. Reactive oxygen species (ROS) are key signaling intermediates in various cellular events, playing critical roles in the physiology of myofibroblasts. However, when dysregulated, these molecules can engage in misinstructive manners with myofibroblasts, directing these cells toward pathogenic states and behaviors. In brief, dysregulated ROS pathologically modulate myofibroblast differentiation, extracellular matrix (ECM) remodeling, and immune evasion, maintaining self-perpetuating cycles of myofibroblast survival. The mediation of ROS promotes maladaptive intra and extracellular responses that contribute to myofibroblast persistence by enhancing ECM stiffness, increasing resistance to apoptosis, inducing senescence, and impairing immune clearance. ROS-mediated alterations in ECM components, most notably in proteoglycans (PGs) and glycosaminoglycans (GAGs), further dysregulate the ECM and make it more conducive to myofibroblast persistence. Additionally, ROS-induced immune privilege mechanisms prevent the proper clearance of myofibroblasts. Therefore, targeting ROS collectively offers promising therapeutic potential for mitigating their pathological presence and behavior, thereby enhancing overall corneal recovery following insults.
Nadeb M, Aghaei SS, Komeili-Movahed T
… +1 more, Afkhami H
Oxid Med Cell Longev
· 2026 · PMID 42273782
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The present document highlights the significance of microbial lipids as new generation anticancer, antitumor, and antioxidant compounds. It focuses on the diverse nature of the action of these lipids in cancer treatment,...The present document highlights the significance of microbial lipids as new generation anticancer, antitumor, and antioxidant compounds. It focuses on the diverse nature of the action of these lipids in cancer treatment, especially polyunsaturated fatty acids (PUFAs). These mechanisms include membrane disruption, apoptosis/necrosis, DNA damage modifying histone and gene expression, angiogenesis inhibition, cell proliferation/cycle regulation, migration, invasion, metastasis, differentiation, reversal of drug resistance, and immune system modulation. The text also discusses the economical biosynthesis of these lipids via microbial fermentation, chemosynthesis, and other synthesis techniques. The versatility of PUFAs is described in detail in the following areas of study including signal transduction and inflammation. While microbial lipids offer potential cost-effectiveness due to scalable fermentation processes, it is important to note that specific clinical dosage regimens and comprehensive pharmacoeconomic comparisons with standard chemotherapeutic agents are still under investigation. Current estimates suggest lower long-term costs if optimized dosing is achieved, but further clinical trials are required to validate these economic benefits.
Rethineswaran V, Hong YJ, Jang WB
… +7 more, Choi J, Lim HJ, Park S, Lee EJ, Ha JS, Yun J, Kwon SM
Oxid Med Cell Longev
· 2026 · PMID 42267664
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Mitochondria are intracellular organelles that regulate cell survival and death. Hyperglycemia modulates the functioning of the mitochondria in endothelial cells. We discovered that high-glucose (HG) treatment reduces FU...Mitochondria are intracellular organelles that regulate cell survival and death. Hyperglycemia modulates the functioning of the mitochondria in endothelial cells. We discovered that high-glucose (HG) treatment reduces FUN14 domain-containing 1 (FUNDC1) expression in endothelial cells. FUNDC1 expression in the mitochondria inhibits the proteasomal degradation of cytochrome C oxidase IV (COX-IV) and regulates mitochondrial complex I and IV activities as well as ATP synthesis under normal conditions. The FUNDC1 depletion in HG contexts affects mitochondrial complex I and IV activity as well as ATP synthesis and promotes mitochondrial damage through the loss of mitochondrial membrane potential and the production of reactive oxygen species (ROS). BAM15 is a mitochondrial uncoupler that increases mitochondrial function and endothelial survival. Cotreatment with HG and BAM15 increased the FUNDC1 protein expression level and the mitochondrial translocation of FUNDC1 in HG-treated cells. The BAM15-induced upregulation of FUNDC1 expression increased the mitochondrial expression of COX-IV, complex I and IV activity, and ATP synthesis. Our findings suggest that FUNDC1 expression in endothelial cells under hyperglycemic stress plays a crucial role in limiting vascular damage and apoptotic cell death. We discovered a mechanism through which BAM15 protects endothelial cells through FUNDC1-mediated mitophagy and metabolic regulation. Targeting FUNDC1 via mitochondrial uncoupling is a promising therapeutic strategy for treating diabetic vascular diseases.
Phang HJ, Arciniega AM, Bergstorm J
… +4 more, Avalon NE, Glukhov E, Gerwick WH, Molina AJA
Oxid Med Cell Longev
· 2026 · PMID 42198997
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While mitochondria are recognized as promising therapeutic targets for common pathologies of aging, existing drug discovery platforms fail to capture the adequate physiological and biological contexts necessary to identi...While mitochondria are recognized as promising therapeutic targets for common pathologies of aging, existing drug discovery platforms fail to capture the adequate physiological and biological contexts necessary to identify translatable, clinically-relevant leads. The goal of this study was to identify marine natural products that modulate mitochondrial function using a screening pipeline leveraging primary human cells in a cell-based phenotypic primary screen. Using this approach, we identified leptochelin A, a recently described metallophore, as a candidate hit with strong potency and efficacy towards the inhibition of mitochondrial function. Using high-resolution respirometry and fluorescence imaging, we validated the mitochondrial-modulatory ("mito-modulatory") effects of leptochelin A and found that it inhibits multiple pathways in the electron transfer system (ETS) while having little effect on mitochondrial mass or superoxide production. It also increases mitochondrial ATP levels, though this may be attributable to a parallel increase in glycolysis. Our findings demonstrate the utility of phenotypic screening using human primary cells to identify novel mitochondrial modulators with translational potential. Leptochelin A's ability to inhibit mitochondrial function without imposing significant toxicity, coupled with its metal-chelating properties, make it a unique compound with therapeutic potential for aging and age-related disorders. Screening strategies focused on mitochondrial respiration can serve as a platform for the advancement of drug discovery within the pharmacology space of human aging.
Atasoy T, Sajedi H, Khodadadi D
… +4 more, Tozoğlu B, Güler MŞ, Aka ST, Babaei M
Oxid Med Cell Longev
· 2026 · PMID 42152587
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NOD-like receptor protein 3 (NLRP3) inflammasome-driven neuroinflammation contributes to Alzheimer's disease (AD) progression, yet effective strategies to target this pathway are limited. We investigated whether aerobic...NOD-like receptor protein 3 (NLRP3) inflammasome-driven neuroinflammation contributes to Alzheimer's disease (AD) progression, yet effective strategies to target this pathway are limited. We investigated whether aerobic exercise performed in a fasted state, rather than the fed state, would potentiate β-hydroxybutyrate (BHB)-dependent inhibition of NLRP3 inflammasome signaling. Twenty-month-old male Wistar rats were randomly assigned to five groups: AD, AD + intermittent fasting (ADIF), AD + aerobic exercise (ADAE), ADIF + aerobic exercise (ADIFAE), and sham-injected control (SC). AD-like pathology was induced by bilateral intrahippocampal injection of amyloid-β (Aβ). The IF regimen consisted of a daily 14-h fast (06:00-20:00). Exercise consisted of moderate-intensity treadmill running (5 days/week for 4 weeks), either in the fed state or after ∼12.5 h of fasting. Aβ injection impaired spatial learning and memory, elevated soluble Aβ (sAβ), malondialdehyde (MDA), NF-κB, NLRP3, caspase-1, interleukin-1β (IL-1β), and IL-18, and reduced superoxide dismutase (SOD) activity and brain-derived neurotrophic factor (BDNF) expression in the hippocampus (p < 0.05). Both IF and exercise partially reversed cognitive impairments by reducing sAβ and oxidative stress, increasing BHB, suppressing NF-κB/NLRP3 signaling, and restoring BDNF (p < 0.05), while fasted-state exercise produced significantly larger effects than either intervention alone (p < 0.05). Our findings suggest that performing exercise in a fasted state provides complementary metabolic, anti-inflammatory, and cognitive benefits that exceed those of either intervention alone. This combined regimen may represent a promising nonpharmacological strategy for targeting metabolic-immune and neurotrophic pathways relevant to AD progression.