bims-mistre 2025-10-26 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–10–26
twelve papers selected by
Ellen Siobhan Mitchell, MitoQ

Ovarian aging: pathophysiology and recent developments in maintaining ovarian reserve.
Mitochondrial dysfunction, reactive oxygen species, and diabetes mellitus - A triangular relationship: A review.
Mitochondrial proteomics reveals the impact of Estrogen in enhancing energy metabolism of patient-derived fibroblast-like synoviocytes in rheumatoid arthritis.
Exploring the role of insulin resistance in bridging the metabolic syndrome and Alzheimer's disease-a review of mechanistic studies.
Mitochondrial dysfunction, a new marker warning of neuropsychiatric disorder risk: evidence from genetics and epidemiology.
Insulin resistance and cognitive decline: the metabolic mechanisms linking type 2 diabetes to Alzheimer's disease.
Genistein ameliorates glucose-induced β-amyloid toxicity, oxidative stress, and aging in the C. elegans model of Alzheimer's disease.
Schisandrin B combined with vitamin D inhibits NLRP3 inflammasome to improve cognitive dysfunction and Alzheimer's disease.
Estrogen in skeletal muscle: metabolism, mechanisms, and exercise-induced changes.
Kynurenine pathway: a possible new mechanism for exercise in the prevention and treatment of Alzheimer's disease.
Mitochondrial fatty acid oxidation is stimulated by red light irradiation.
Isoflavones improve vaginal atrophy, skin health, and sex-related hormones in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

Front Endocrinol (Lausanne). 2025 ;16 1619516

Ovarian aging: pathophysiology and recent developments in maintaining ovarian reserve.

Mana Hirano, Takako Onodera, Kazuki Takasaki, Yuko Takahashi, Takayuki Ichinose, Haruka Nishida, Haruko Hiraike, Kazunori Nagasaka.

  According to the World Health Organization, infertility has emerged as a critical public health issue, affecting approximately 48 million couples and 186 million individuals worldwide. Ovarian aging-defined by the progressive depletion and functional deterioration of the primordial follicle pool-accounts for a major proportion of female-factor infertility and has profound socioeconomic consequences. It is characterized by a decline in follicle quantity and quality, which significantly influences infertility. This phenomenon is multifaceted, involving genetic predisposition, hormonal fluctuations, mitochondrial dysfunction, oxidative stress, and ovarian microenvironment alterations. This review explores the biological mechanisms of ovarian aging, evaluates current therapeutic advances, and identifies strategies to maintain ovarian function and prolong reproductive lifespan. Recent advancements-including antioxidant and mitochondria-targeted therapies, hormonal modulation, growth factor interventions (e.g., platelet-rich plasma), mitochondrial transfer, and in vitro follicle activation-show promise for maintaining ovarian reserve. Fertility preservation strategies, such as ovarian tissue cryopreservation and transplantation, and pharmacological inhibition of follicle depletion, have expanded therapeutic options. The development of personalized treatments, refined biomarkers, and integrative strategies combining antioxidants, hormonal therapies, and novel fertility preservation techniques is essential. Therefore, translational research utilizing animal models remains crucial for validating efficacy and safety prior to clinical application. Future research should prioritize validating these emerging therapies through larger clinical trials to ensure safe, effective, and practical translation into clinical practice, ultimately prolonging reproductive lifespan and enhancing quality of life for aging women.

Keywords:  biomarker-driven; delayed parenthood; fertility preservation; follicle depletion; hormonal therapies; menopause; ovarian aging; ovarian reserve

DOI:  https://doi.org/10.3389/fendo.2025.1619516
Biomol Biomed. 2025 Oct 23.

Mitochondrial dysfunction, reactive oxygen species, and diabetes mellitus - A triangular relationship: A review.

Mia Manojlovic, Sonja Zafirovic, Dragana Tomic Naglic, Edita Stokic, Manfredi Rizzo, Jasjit S Suri, Esma Isenovic.

Diabetes mellitus (DM) disrupts cellular homeostasis and is characterized by mitochondrial structural and functional impairments similar to those found in other metabolic disorders. Mitochondrial dysfunction (MD) leads to the excessive production of reactive oxygen species (ROS), which are central to the progression of cardiovascular (CV) disease-the leading cause of mortality associated with DM. ROS-driven oxidative stress (OS) is implicated in cardiac injury in both clinical and experimental contexts. This review synthesizes recent literature on the role of MD in the development and progression of DM and its associated CV complications, highlighting disrupted pathways that regulate the balance between ROS production and antioxidant defenses. We summarize alterations in mitochondrial dynamics-including fusion, fission, and mitophagy-mtDNA damage, and impaired oxidative phosphorylation characterized by dysregulated mitochondrial membrane potential (ΔΨm), electron transport chain (ETC) defects, uncoupling, and substrate overload. Additionally, we discuss hyperglycemia-activated pathways such as polyol flux, AGE-RAGE interactions, protein kinase C/nicotinamide adenine dinucleotide phosphate (PKC/NADPH) oxidase activation, and poly(ADP-ribose) polymerase 1 (PARP-1)-mediated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibition, which contribute to inflammation, endothelial dysfunction, β-cell failure, insulin resistance, and micro/macrovascular injury. Diagnostic and biomarker strategies encompass mtDNA analysis, bioenergetic assays, metabolomics, proteomics, and imaging techniques including PET, MRI, and NIRS. Therapeutic approaches aimed at restoring mitochondrial function and mitigating OS include mitochondria-targeted antioxidants (such as MitoQ, CoQ10, SkQ1, SS-31, and Mito-TEMPO), metabolic drugs (including metformin and SGLT2 inhibitors), lifestyle modifications, and emerging gene-editing technologies. The interplay between mitochondria, ROS, and DM reflects a tightly regulated aspect of cellular physiology; while targeted and personalized strategies hold promise, they necessitate rigorous evaluation.

DOI: https://doi.org/10.17305/bb.2025.13145
Inflamm Res. 2025 Oct 22. 74(1): 146

Mitochondrial proteomics reveals the impact of Estrogen in enhancing energy metabolism of patient-derived fibroblast-like synoviocytes in rheumatoid arthritis.

Swati Malik, Debolina Chakraborty, Prachi Agnihotri, Ashish Sarkar, Lovely Joshi, Mohd Saquib, Vijay Kumar, Sagarika Biswas.

  Mitochondrial dysfunction drives Rheumatoid Arthritis (RA) progression by disturbing energy metabolism and promoting inflammation. Additionally, the female predominance of RA highlights estrogen deficiency as an important contributor to disease development. The effect of estrogen in RA has been investigated; however, its specific effects on the mitochondrial proteome and function have yet to be studied. This study investigated the effects of 17-β estradiol (E2) on the mitochondrial proteome of patient-derived RA fibroblast-like synoviocytes (RA-FLS) using Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS) analysis, followed by an assessment of key mitochondrial functional parameters and in vitro validation. The results identified an upregulated expression of two mitochondrial proteins, Acyl-CoA dehydrogenase very long chain (ACADVL) and ATP synthase subunit O (ATP5O), after E2 treatment in RA-FLS. This was further validated by increased real-time ATP production and reduced glycolytic capacity, along with increased expression of proteins related to fatty acid β-oxidation. In addition, E2 influenced mitochondrial dynamics by modulating the fission-fusion balance, resulting in improved mitochondrial morphology. E2 treatment also reduced the expression of mitophagy markers and increased mitochondrial membrane potential, indicating improved mitochondrial function. It also lowered mitochondria-centered oxidative stress by upregulating mitochondrial antioxidant enzymes. Mitochondrial proteomics analysis thus, demonstrated that E2 has the potential to enhance mitochondrial energy metabolism and alleviate mitochondrial dysfunction in RA. These findings provide a foundation for further exploration of mitochondria-targeted therapeutic approaches in RA management.

Keywords:  Energy metabolism; Estrogen; Mitochondria; Mitochondrial proteomics; Rheumatoid arthritis; Synovial fibroblast

DOI:  https://doi.org/10.1007/s00011-025-02120-6
Front Endocrinol (Lausanne). 2025 ;16 1614006

Exploring the role of insulin resistance in bridging the metabolic syndrome and Alzheimer's disease-a review of mechanistic studies.

Shilei Wang, Yuqing Shi, Rui Xin, Hailan Kang, Huazhong Xiong, Jixiang Ren.

  The association between metabolic syndrome (MetS) and Alzheimer's disease (AD) has attracted widespread attention; nevertheless, the precise mechanism of action between the two is not yet fully elucidated. This review systematically explores the complex mechanisms of insulin resistance (IR) in MetS and AD. We first detail the intrinsic mechanisms of insulin resistance and emphasize its central role in the pathophysiology of MetS. Further, we reveal the underlying mechanisms by which insulin resistance in turn triggers AD through a multidimensional pathway that promotes the accumulation of pathological products, induces blood-brain barrier dysfunction, impairs neuroplasticity, induces neuroinflammatory responses, aberrantly activates the renin-angiotensin-aldosterone system, and exacerbates oxidative stress. In addition, we summarize potential strategies for targeting IR in AD treatment and demonstrate the promising prospects for improving insulin resistance in promoting cognitive recovery. This study offers a novel theoretical framework for elucidating the intricate relationship between MetS and AD. Furthermore, it provides a scientific foundation for the formulation of preventive and therapeutic strategies for metabolic and neurodegenerative diseases.

Keywords:  Alzheimer’s disease; cognitive impairment; insulin resistance; mechanism research; metabolic syndrome

DOI:  https://doi.org/10.3389/fendo.2025.1614006
Ann Gen Psychiatry. 2025 Oct 22. 24(1): 64

Mitochondrial dysfunction, a new marker warning of neuropsychiatric disorder risk: evidence from genetics and epidemiology.

Qingan Fu, Jizhen Li, Huangxin Zhu, Qingyun Yu, Tianzhou Shen, Zhekang Liu, Yue Liu, Wei Zhou.

   BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of neuropsychiatric disorders, but its causal role remains unclear. Mitochondrial DNA copy number (mtDNA-CN) and methylmalonic acid (MMA) are well-recognized biomarkers of mitochondrial function, but their association with psychiatric disorders has not yet been fully assessed.
METHODS: We performed two-step two-sample Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data to assess causal associations between mtDNA-CN and 13 major neuropsychiatric disorders. In addition, we conducted a cross-sectional analysis using National Health and Nutrition Examination Survey (NHANES) data 2011-2014 to examine the association between serum MMA levels and cognitive impairment and depressive symptoms to further validate the correctness and robustness of the results of the MR analysis.
RESULTS: MR analysis showed a significant negative causal effect of mtDNA-CN on bipolar disorder, Alzheimer's disease, dementia, depressive symptoms, and autism spectrum disorders (OR ranged from 0.15 to 0.84, all p < 0.05). Reverse MR analysis showed that only depressive symptoms had a significant causal effect on reducing mtDNA-CN. NHANES analysis further showed that higher MMA levels were significantly associated with an increased risk of cognitive impairment (OR = 1.56, p = 0.036) and depression (OR = 1.53, p = 0.020), suggesting that mitochondrial dysfunction and neuropsychiatric disorders have a close association.
CONCLUSION: The mitochondrial function biomarkers mtDNA-CN and MMA are expected to be potential therapeutic targets for depression and cognitive dysfunction, emphasizing the need for mitochondrial function monitoring and interventions in future therapies targeting neuropsychiatric disorders.

Keywords:  Mendelian randomization; Methylmalonic acid; Mitochondrial dysfunction; MtDNA copy number; Neuropsychiatric disorders

DOI:  https://doi.org/10.1186/s12991-025-00604-7
Diabetol Int. 2025 Oct;16(4): 614-629

Insulin resistance and cognitive decline: the metabolic mechanisms linking type 2 diabetes to Alzheimer's disease.

Haya Majid, Mansi Dahalia, Shadan Hussain, Sparsh Saini, Nidhi.

   Background: Alzheimer's disease (AD) and Type 2 Diabetes Mellitus (T2DM) share overlapping pathophysiological pathways, including metabolic reprogramming, oxidative stress, and impaired cellular homeostasis.
Methods: This review explored the role of metabolism in mediating these processes and its implications for neurodegeneration and metabolic dysfunction in T2DM and AD. A detailed analysis of the current literature was performed using MESH terms on relevant databases (Google Scholar, PubMed, Embase, and Cochrane Library) to systematically observe the causes of cognitive impairment.
Results: Overexpression of Branched Chain Amino Acid (BCAA) is linked to significant disruptions in glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation, leading to reduced acetyl-CoA availability and increased production of reactive oxygen species (ROS). These metabolic disturbances contribute to dysregulated autophagy and the accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau. High glucose levels, characteristic of T2DM, exacerbate Branched Chain Amino T 1-associated dysregulation, amplifying neuronal death and oxidative damage. Interestingly, BCAA supplementation helps counteract certain negative effects by boosting ATP production, indicating a dual role in the progression of the disease. Additionally, the interactions with redox-sensitive enzymes and autophagy pathways further provide evidence of its role in regulating cellular homeostasis.
Conclusion: These findings provide a base for researchers for further research on metabolic pathway modulation, advanced biomarker discovery, precision medicine, targeted antioxidant therapies, and AI-driven predictive modelling. Novel BCAA modulators offer a promising therapeutic direction, potentially bridging the gap between metabolic and neurodegenerative disorders, providing a foundation for innovative interventions in cognitive impairment.

Keywords:  Autophagy dysregulation; Branched-chain amino acid transaminase; Cognitive impairment; Metabolism; Oxidative stress

DOI:  https://doi.org/10.1007/s13340-025-00830-0
Free Radic Biol Med. 2025 Oct 21. pii: S0891-5849(25)01277-8. [Epub ahead of print]

Genistein ameliorates glucose-induced β-amyloid toxicity, oxidative stress, and aging in the C. elegans model of Alzheimer's disease.

Jingwen Wang, Bochen Jiang, Xiaojun Lin, Jingyang Zhang, Liyang Xiong, Yuqing Feng, Wai San Cheang, Baojun Xu.

  Alzheimer's disease (AD) has been considered a kind of diabetic encephalopathy due to the shared molecular mechanisms found between type 2 diabetes mellitus (T2DM) and AD. However, the specific mechanism and therapy of diabetic encephalopathy remain underexplored, particularly the neuroprotective potential of dietary polyphenols in conditions of glucose enrichment. In this study, glucose enrichment-induced potentially harmful effects regarding (neuro)toxicity, apoptosis, oxidative stress, and impaired lipid metabolism were reported for the first time in the AD Caenorhabditis elegans model (CL4176 and CL2355). Genistein intervention prolonged the lifespan and mitigated AD-like symptoms in C. elegans. Further results from network pharmacology, RNA sequencing, RT-qPCR, and lipidomic analysis revealed that the anti-aging, antioxidative, and neuroprotective effects of genistein involve the regulation of sphingolipids, glycerophospholipids, and glycerolipids, which are likely mediated via the PI3K/AKT signaling pathway. These findings provide novel insights into the role of dietary polyphenols in preventing cognitive impairment and aging.

Keywords:  Aging; Amyloid-β; Diabetic Encephalopathy; Genistein; Lipidomics; Network pharmacology; Neurotoxicity; Oxidative stress

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.10.263
Eur J Pharmacol. 2025 Oct 17. pii: S0014-2999(25)01022-2. [Epub ahead of print]1007 178268

Schisandrin B combined with vitamin D inhibits NLRP3 inflammasome to improve cognitive dysfunction and Alzheimer's disease.

Yu Wang, Lili Deng, Lianghui Wang, Wen Liu.

   PURPOSE: This study investigates the therapeutic effects of Schisandrin B (Sch B) combined with vitamin D (VD) on cognitive dysfunction and Alzheimer's disease (AD)-like pathology in aged rats induced by a high-fat and high-sugar (HFHS) diet, with a focus on the inhibition of NLRP3 inflammasome activation as a potential mechanism.
METHODS: Eighteen-week-old male Sprague-Dawley rats were randomly assigned to five groups: Control, HFHS, HFHS + Sch B, HFHS + VD, and HFHS + Sch B + VD. After 20 weeks of treatment, metabolic parameters (body weight, fasting blood glucose, insulin resistance, lipid profiles), inflammatory markers, and hippocampal protein expression were assessed. Cognitive function was evaluated using the Morris water maze, novel object recognition, open field, and elevated plus maze tests.
RESULTS: Combined Sch B and VD markedly attenuated body weight gain, fasting blood glucose, fasting serum insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), while improving lipid profiles (TG, TC, LDL-C). Behavioral tests revealed significant improvements in spatial learning, memory, and object recognition (p < 0.01), with combined therapy outperforming monotherapy. Additionally, the combination downregulated hippocampal NLRP3 inflammasome components (ASC, cleaved caspase-1, IL-1β, IL-18) and reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).
CONCLUSION: In this HFHS diet-induced aging rat model, Sch B combined with VD improved cognitive performance and reduced AD-like lesions, likely via inhibition of NLRP3 inflammasome-mediated neuroinflammation. These findings provide mechanistic insights and support further preclinical evaluation of this combination as a potential strategy for AD prevention and intervention.

Keywords:  Alzheimer's disease; Cognitive dysfunction; NLRP3 inflammasome; Schisandrin B; Vitamin D

DOI:  https://doi.org/10.1016/j.ejphar.2025.178268
J Endocrinol Invest. 2025 Oct 21.

Estrogen in skeletal muscle: metabolism, mechanisms, and exercise-induced changes.

Yiwei Feng, Rengfei Shi.

  With the intensification of population aging, issues such as age-related skeletal muscle loss and metabolic disorders have garnered increasing attention. As the menopausal transition progresses, circulating estrogen levels decline, making locally synthesized estrogen in peripheral tissues particularly important. In addition to the ovaries, steroidogenic enzymes are present in skeletal muscle, enabling the local synthesis of myogenic estrogen. Myogenic estrogen can regulate muscle function and metabolism in an autocrine or paracrine manner within skeletal muscle tissue. Exercise, as a safe and effective non-pharmacological intervention, has been shown to regulate estrogen levels in skeletal muscle. Exercise may promote the synthesis of myogenic estrogen by enhancing the expression of estrogen precursor substances and steroidogenic enzymes in skeletal muscle, thereby improving skeletal muscle function and metabolism. This review summarizes the structure and function of estrogen receptors in skeletal muscle, the synthesis and metabolism of myogenic estrogen, the roles and mechanisms of estrogen in skeletal muscle, and the mechanisms underlying the influence of exercise on estrogen synthesis in skeletal muscle.

Keywords:  Aromatase; Estrogen; Exercise; Postmenopausal females; Skeletal muscle

DOI:  https://doi.org/10.1007/s40618-025-02726-x
Front Aging Neurosci. 2025 ;17 1617690

Kynurenine pathway: a possible new mechanism for exercise in the prevention and treatment of Alzheimer's disease.

Gangqiang Li, Shuang Li, Wenhui Zhou.

  Alzheimer's disease (AD) is the most common neurodegenerative disease in clinical practice. The kynurenine pathway (KP) is a potential intersection of factors associated with the development of AD (central nervous inflammation, glutamate excitotoxicity, and tau phosphorylation, among others). Pharmacological modulators targeting KP enzymes, such as inhibitors or agonists, and their major neuroprotective metabolites are beneficial in alleviating AD progression. Exercise significantly improves AD symptoms and also impacts KP pharmacokinetics. Promoting the production of neuroprotective active metabolites by KP may be one of the central mechanisms by which exercise improves AD symptoms. This article reviews the possible role of KP in AD neurodegeneration and AD exercise prevention and treatment.

Keywords:  Alzheimer's disease; exercise; kynurenic acid; kynurenine pathway; quinolinic acid

DOI:  https://doi.org/10.3389/fnagi.2025.1617690
FEBS Lett. 2025 Oct 18.

Mitochondrial fatty acid oxidation is stimulated by red light irradiation.

Manuel Alejandro Herrera, Camille C Caldeira da Silva, Maiza Von Denz, Mauricio S Baptista, Alicia J Kowaltowski.

  Keratinocytes are the primary constituents of sunlight-exposed epidermis. In these cells, ultraviolet (UV) A light completely inhibited oxidative phosphorylation, while equivalent doses of blue and green light preserved metabolic fluxes but reduced viability. In contrast, red light enhanced proliferation and elevated basal and maximal oxygen consumption rates for 48 h without altering protein levels of the electron transport chain. Targeted flux analysis revealed that red light specifically activates AMP-activating protein kinase (AMPK)-dependent mitochondrial fatty acid oxidation. This was accompanied by reduced levels of free fatty acids and increased acetyl-CoA carboxylase phosphorylation. Together, our results characterize wavelength-selective regulation of keratinocyte metabolism: UV/visible wavelengths induce damage, while red light triggers AMPK-dependent fatty acid oxidation, providing a mechanistic explanation for photobiomodulation in epidermal cells. Impact statement Sunlight impacts skin cells in surprising ways. While UVA harms energy production and blue/green light reduces survival, red light boosts keratinocyte metabolism. We show that red light activates AMPK-dependent fatty acid oxidation, enhancing proliferation and energy use. These findings reveal how specific wavelengths can damage or stimulate skin cells.

Keywords:  AMPK; beta oxidation; light; metabolism; mitochondria; skin

DOI:  https://doi.org/10.1002/1873-3468.70195
Menopause. 2025 Oct 21.

Isoflavones improve vaginal atrophy, skin health, and sex-related hormones in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

Mingkwan Na Takuathung, Ratchanon Inpan, Kantirat Yaja, Wilawun Ruansit, Supanimit Teekachunhatean, Nut Koonrungsesomboon.

   IMPORTANCE: Isoflavones, natural bioactive compounds with estrogen-like properties, are increasingly used by postmenopausal women to manage menopausal symptoms. However, research on their efficacy has produced inconsistent results, necessitating a comprehensive review to guide clinical practice.
OBJECTIVE: To evaluate the effects of isoflavone interventions on vaginal atrophy, skin health, and sex-related hormone levels in postmenopausal women through a systematic review and meta-analysis of randomized controlled trials.
EVIDENCE REVIEW: A systematic literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases from inception to January 2025. Eligible studies were randomized controlled trials investigating isoflavone interventions in postmenopausal women. Effect sizes were summarized as standardized mean differences (SMDs) with 95% CIs using a random-effects model. The risk of bias was assessed using the Risk of Bias 2 tool.
FINDINGS: The analysis included 47 studies comprising 2,657 participants. Isoflavone interventions significantly reduced vaginal dryness (SMD=-1.147; 95% CI, -2.077 to -0.216; P=0.016; I2=95.4%) and increased the vaginal maturation value (SMD=0.605; 95% CI, 0.087 to 1.123; P=0.022; I2=88.7%). Improvements in skin health were observed, including reduced skin roughness measure R2 (SMD=-0.209; 95% CI, -0.389 to -0.029; P=0.028; I²=0.0%) and wrinkle surface (SMD=-0.342; 95% CI, -0.560 to -0.124; P=0.002; I2=0.0%). Isoflavones also significantly increased estradiol levels (SMD=0.247; 95% CI, 0.059 to 0.435; P=0.010; I2=60.5%).
CONCLUSIONS AND RELEVANCE: Isoflavone interventions effectively manage vaginal atrophy in postmenopausal women and show potential for improving skin health and sex-related hormone levels. These findings underscore the therapeutic value of isoflavones while emphasizing the need for further research, particularly regarding their effects on skin health.

Keywords:  Isoflavones; Menopause; Postmenopausal women; Sex-related hormone; Skin health; Vaginal atrophy

DOI:  https://doi.org/10.1097/GME.0000000000002619