bims-mistre 2026-09-13 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2026–09–13
nineteen papers selected by
Ellen Siobhan Mitchell, MitoQ

Mitochondria in health and disease: cellular powerhouses, signaling centers, and drivers of dysfunction.
GPER stimulation attenuates mitochondrial dysfunction and cardiac dysfunction in ovariectomized mice with heart failure with preserved ejection fraction (HFpEF).
Mitochondrial Haplotype Shapes the Trajectory of Ovarian Aging in Genetically Heterogeneous Rats.
Mitochondrial homeodynamics in ageing: mechanisms, resilience, and interventions.
Preserved mitochondrial respiration in presence of oxidative stress and reduced mitochondrial mass after 10-day bed rest in older adults.
Targeting Mitochondria in MASLD: Comparative Evaluation of MitoQ and SS-31 (Elamipretide) in Aged Female Mice under Nutritional Stress.
Dual miRNA-Mediated Axes Act in Concert in the Antioxidant Action of Eicosapentaenoic Acid: let-7c-3p/TFAM Drives Mitochondrial Biogenesis While miR-34c-5p/SIRT1 Potentiates Enzymatic Defenses.
Reproductive lifespan in relation to diabetes mellitus and metabolic syndrome in a nationally representative population.
Mitochondrial Proteostasis Links Diabetes and Sarcopenia: Cross-Scale Convergence from Experimental Models to Human Multi-Omics.
Targeting TWEAK to enhance mitochondrial biogenesis and attenuate age-related muscle mass loss.
Epigallocatechin Gallate From Tea Delays Oocyte Aging After Ovulation in Mice.
Menopausal Hormone Therapy and Cardiovascular Risk in Midlife Women With Vasomotor Symptoms.
Menopausal Hormone Treatment as a Preventive against the Progress of Chronic Diseases in Menopausal Women.
β-Hydroxybutyrate-induced mitochondrial dysfunction and oxidative stress in BMSCs are ameliorated by mitophagy activation.
Bioinspired plant-derived extracellular vesicles enabling dual-targeting therapy for primary ovarian insufficiency.
Effects of Vitamin D Supplemental Dose in Adults with Prediabetes: A Systematic Review and Network Meta-Analysis.
Ergothioneine, collagen peptides, and sodium hyaluronate ameliorate facial skin aging via modulating oxidative stress, inflammation, and extracellular matrix homeostasis.
The Silent Vascular Shift: Endothelial Dysfunction and Cardiovascular Risk in Menopausal Women.
Mitochondrial homeostasis and aging: the mtDNA-cGAS-STING axis.

Front Cell Dev Biol. 2026 ;14 1929130

Mitochondria in health and disease: cellular powerhouses, signaling centers, and drivers of dysfunction.

Olufemi Akintayo Akinkunmi, Feyikemi Funmilayo Araba, Jessica Adaeze Chukwudebelu, Victor Ademola Adenle, Ajibola Ayomide Odeyemi, Tunmise Maryanne Akhigbe, Roland Eghoghosoa Akhigbe.

  Although the mitochondria are known as the cellular powerhouse, their function is beyond energy generation. These organelles regulate cellular metabolism, yet maintains a tightly regulated reactive oxygen species (ROS) generation and optimal redox state. In addition, mitochondria serve as mediators of physiological and pathological processes, such as maintenance of calcium balance, and control of apoptosis and mitophagy. All these make the mitochondria a major factor in both cellular and organismal regulation. However, mitochondria dysfunction may occur through many processes, including genetic mutations, increased production of ROS, metabolic failure from impaired electron transport chain activity, and dysregulated dynamics or mitophagy. Several self-perpetuating damages accumulate from these processes and influence clinical pathologies, such as aging, metabolic syndrome, cancer, neurodegeneration, and reproductive disorders. Recent studies demonstrate promising therapeutic targets for mitochondrial dysfunction. Examples include targeted antioxidants, such as MitoQ and SkQ1, to selectively neutralize mitochondrial ROS, pharmacological modulators to enhance mitochondrial biogenesis and to restore NAD+ homeostasis via PGC-1α activation, gene-editing technologies, such as mitoTALENs and mtZFNs to selectively eliminate pathogenic mitochondrial DNA mutations, and mitochondrial transplantation as a new technique to replace damaged organelles. Together, these novel approaches highlight the need for research in mitochondrial function to change the therapeutic landscape in the management of mitochondrial dysfunction-associated diseases.

Keywords:  ROS; mitochondria; mitochondrial dysfunction; mitochondrial transplantation; mitophagy; oxidative phosphorylation

DOI:  https://doi.org/10.3389/fcell.2026.1929130
Br J Pharmacol. 2026 Sep 10.

GPER stimulation attenuates mitochondrial dysfunction and cardiac dysfunction in ovariectomized mice with heart failure with preserved ejection fraction (HFpEF).

Miaomiao Qi, Runmin Sun, Qiongying Wang, Lulu Zhu, Mingze Li, Wenting Wang, Xin Fan, Jing Yu.

   BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is prevalent among postmenopausal women and is strongly linked to estrogen deficiency. G-protein coupled estrogen receptor (GPER) mediates non-genomic estrogen signalling and exerts cardiovascular protective effects. Its role in the pathogenesis of HFpEF remains unclear. This study aimed to explore whether GPER activation could attenuate mitochondrial dysfunction and cardiac damage in ovariectomized (OVX) mice with HFpEF.
METHODS: Circulating GPER levels were measured in postmenopausal women with HFpEF and healthy controls. A correlation analysis was performed to assess the associations between GPER and cardiac function. Female C57BL/6J mice underwent ovariectomy and were fed with high-fat diet and l-NAME to induce HFpEF. Mice were treated with the GPER agonist G-1 for 4 weeks. Cardiac function, histological changes, oxidative stress, mitochondrial function and mitophagy were evaluated in vivo and in vitro.
RESULTS: Serum GPER levels were significantly higher in postmenopausal women with HFpEF and correlated with NT-proBNP and E/e'. In OVX mice with HFpEF, GPER expression was up-regulated, and G-1 improved diastolic function, reduced myocardial hypertrophy and oxidative stress. Importantly, G-1 restored mitochondrial ATP production, normalized mitochondrial dynamics and promoted mitophagy in vivo and in vitro. These effects were associated with activation of the AMPK/ULK1 pathway. Inhibition of AMPK diminished the protective effects of G-1 in cardiomyocytes.
CONCLUSIONS: GPER agonist G-1 ameliorated mitochondrial dysfunction, promoted mitophagy and alleviated cardiac diastolic dysfunction in OVX mice with HFpEF, partially through the AMPK/ULK1 pathway, indicating GPER as a therapeutic target for postmenopausal women with HFpEF.

Keywords:  AMPK/ULK1 signalling pathway; G‐protein coupled estrogen receptor; heart failure with preserved ejection fraction; mitochondrial dysfunction; mitophagy; postmenopausal women

DOI:  https://doi.org/10.1111/bph.70661
Aging Cell. 2026 Sep;25(9): e70710

Mitochondrial Haplotype Shapes the Trajectory of Ovarian Aging in Genetically Heterogeneous Rats.

Subhasri Biswas, Hoang V M Nguyen, Aubrey Converse, Satoshi Matsuzaki, Michael T Kinter, Kenneth M Humphries, Willard M Freeman, Sarah R Ocañas, Arlan Richardson, Francesca E Duncan, Tommy L Lewis, Michael B Stout.

  Ovarian aging leads to permanent reproductive senescence and systemic hormonal changes that predispose women to age-associated comorbidities. Despite these observations, the intrinsic mechanisms driving age-related ovarian decline are poorly defined. Mitochondrial DNA (mtDNA) mutations and instability are strongly associated with aging; however, it remains unknown if naturally occurring mitochondrial genetic variation influences the trajectory of ovarian aging. To address this, we compared two genetically heterogeneous rat cohorts (OKC-HETB and OKC-HETW) that differ in mitochondrial haplotype on a randomized but equivalently distributed nuclear background. The OKC-HETW haplotype was associated with accelerated loss of primordial follicles and pathological remodeling marked by fibrosis, macrophage infiltration, and multinucleated giant cells. These tissue-level pathologies were paralleled by mitochondrial dysfunction, characterized by decreased respiratory complex activity, ATP production, and mtDNA copy number. Mechanistically, we identified a haplotype-specific defect in mitochondrial genome maintenance. Although TFAM expression was normal, and total TFAM protein was elevated, OKC-HETW ovaries showed reduced mitochondrial TFAM abundance, TFAM-mtDNA binding, and TOMM20, suggesting that impaired TOMM20-mediated import is associated with compromised mitochondrial genomic stability. Longitudinal transcriptomic and proteomic analyses further indicate that mitochondrial haplotype influences the rate of ovarian aging, with OKC-HETW ovaries showing accelerated activation of inflammatory and fibrotic pathways alongside suppressed proteostasis and mitochondrial function. These defects corresponded to impairments in ovulation and a trend toward worsening oocyte quality. Collectively, our findings identify mitochondrial haplotype as a heritable modifier of ovarian aging rate that acts in concert with the nuclear genome, and a putative target for preserving ovarian function and female healthspan.

Keywords:  anti‐Müllerian hormone; follicle; haplogroup; menopause; oxidative phosphorylation; rat; reproductive senescence

DOI:  https://doi.org/10.1111/acel.70710
Biogerontology. 2026 Sep 10. pii: 160. [Epub ahead of print]27(5):

Mitochondrial homeodynamics in ageing: mechanisms, resilience, and interventions.

Piotr Paweł Chmielewski.

  Mitochondria integrate bioenergetics, redox signalling, calcium handling, biosynthesis, apoptosis, and stress responses. Their contribution to ageing depends less on any single pathway than on the ability to sustain these functions through continuous maintenance, remodelling, and inter-organelle communication. This review proposes mitochondrial homeodynamics as a systems-level framework for that ability, which rests not on static preservation but on three linked capacities. Maintenance safeguards mitochondrial genome, proteome, and membrane integrity. Adaptation adjusts metabolism and remodels network and cristae architecture to match changing demand. Recovery restores function and reserve after challenge. These capacities emerge from mitochondrial quality control, network and cristae remodelling, biogenesis, mitophagy, retrograde stress signalling, and inter-organelle communication. So defined, mitochondrial dysfunction becomes a measurable loss of capacity rather than a descriptive category. Ageing erodes these capacities in tissue- and context-specific ways, which reduces physiological reserve, slows recovery after stress, and amplifies sterile inflammation. The mechanisms underlying these capacities, the biomarkers that report them, and the interventions proposed to preserve them are evaluated in turn. Exercise provides the strongest human evidence for coordinated mitochondrial and functional adaptation, whereas evidence for energy restriction, NAD+ precursors, mitophagy-supporting compounds, and mitochondria-targeted agents remains heterogeneous and endpoint-specific. No mitochondrial intervention has been shown to slow ageing or extend lifespan in healthy humans, and movement of a biomarker towards a younger reference value does not establish rejuvenation. Progress will require dynamic measures of maintenance, adaptation, and recovery, obtained in defined tissues and interpreted alongside clinically meaningful outcomes.

Keywords:  Ageing; Biomarkers; Exercise; Homeodynamics; Inflammageing; Mitochondria; Mitophagy

DOI:  https://doi.org/10.1007/s10522-026-10506-0
J Physiol. 2026 Sep 11.

Preserved mitochondrial respiration in presence of oxidative stress and reduced mitochondrial mass after 10-day bed rest in older adults.

Evgeniia Motanova, Lucrezia Zuccarelli, Evgenii Lysenko, Stefano Amoretti, Marco Pirazzini, Ornella Rossetto, Lorenza Brocca, Roberto Bottinelli, Maria Antonietta Pellegrino, Giovanni Baldassarre, Clarissa Gissi, Giovanna Lippe, Mladen Gasparini, Boštjan Šimunic, Rado Pišot, Bruno Grassi, Marco V Narici.

  Ageing affects mitochondrial integrity in skeletal muscle, and physical inactivity may further exacerbate these changes. Although mitochondrial alterations are documented in ageing and disuse independently, how disuse impacts the mitochondrial phenotype in older populations remains unclear. This work aimed to characterise how physical inactivity impacts mitochondrial function, morphology and gene expression in the skeletal muscle of older adults. Ten healthy older men (65+ years) underwent 10 days of bed rest. Skeletal muscle biopsies were collected before and after bed rest to assess mitochondrial respiration (high-resolution respirometry), H2O2 emission, mitochondrial protein expression, morphology and volume density (electron microscopy) and transcriptomic profile. Ten days of inactivity increased mitochondrial reactive oxygen species (ROS) emission under non-phosphorylating conditions but did not impair oxidative phosphorylation (OXPHOS) capacity, indicating preserved respiratory efficiency. Consistently, mitochondrial respiratory complex and supercomplex protein abundance were unchanged. Mitochondrial mass decreased, as shown by reduced mitochondrial volume density. Reduced dynamin-like protein 1 (DRP1) phosphorylation at serine 637 was observed, whereas other mitochondrial fission and fusion protein levels remained unchanged. Mitochondrial morphology remained unaltered. Transcriptomic analysis revealed >3000 differentially expressed genes, characterised by downregulation of oxidative phosphorylation genes alongside altered mitophagy, antioxidant and oxidoreductase pathways. In summary, 10-day bed rest increased mitochondrial ROS emission and reduced mitochondrial mass in older skeletal muscle despite preserved respiratory function, indicating that elevated ROS production occurs upstream of respiratory dysfunction and is potentially linked to impaired antioxidant defence and ROS clearance. These findings suggest that preserving redox balance during inactivity may be a key strategy to maintain muscle health and functional independence in ageing populations. KEY POINTS: The impact of short-term physical inactivity on mitochondrial function within the context of ageing remains poorly defined. This study examined the impact of 10-day bed rest on skeletal muscle mitochondrial function, morphology and gene expression in older adults. Short-term inactivity increased mitochondrial ROS production, accompanied by a dysregulation of antioxidant and oxidoreductase genes, indicating a reduced capacity for ROS clearance. Mitochondrial respiration was preserved under both submaximal and maximal stimulation. When normalised to mitochondrial content (citrate synthase activity), respiratory capacity increased, suggesting improved intrinsic efficiency. Mitochondrial mass was reduced, supported by decreased mitochondrial volume density assessed morphologically. Transcriptomic alterations in the mitophagy pathway suggest a potential role of altered mitochondrial degradation in this reduction. These findings indicate a transient compensatory response of ageing mitochondria to short-term disuse, suggesting that functional impairments are likely driven by cardiovascular and microvascular factors rather than mitochondrial respiration itself.

Keywords:  OXPHOS; ROS; inactivity; mitochondria; mitochondrial dynamics; oxidative metabolism

DOI:  https://doi.org/10.1113/JP291588
Physiol Res. 2026 Aug 31. 75(4): 699-714

Targeting Mitochondria in MASLD: Comparative Evaluation of MitoQ and SS-31 (Elamipretide) in Aged Female Mice under Nutritional Stress.

Di Xiao, Xingxing Cui, Sajad Ali, Changfei Li, Bin Wang.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a major cause of cirrhosis, liver cancer, and cardiovascular disease. Early mitochondrial dysfunction drives lipid imbalance, inflammation, and fibrosis. Given the lack of approved pharmacological treatments, this study compares the mitochondria-targeted agents MitoQ and SS-31 for their effects on mitochondrial function, oxidative stress, apoptosis, and inflammation in aged, nutritionally stressed mice with MASLD. Aged female C57BL/6 mice (12-14 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD. Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg/kg/day, oral), and (iv) MASLD + SS-31 (3 mg/kg/day, i.p.). Liver tissues were analyzed by western blotting for mitochondrial biogenesis and dynamics markers (PGC-1?, NRF1, and TFAM), oxidative stress regulators (SOD2, Nrf2, 4-HNE), apoptosis-related proteins (Bax, and Bcl-2), inflammatory and fibrotic mediators (NF-?B, and NLRP3), and insulin signaling proteins (p-Akt, and GLUT2). Both MitoQ and SS-31 significantly improved mitochondrial protein expression and overall liver health compared with untreated MASLD mice. MitoQ primarily enhanced mitochondrial antioxidant defenses by upregulating SOD2 and Nrf2 while decreasing 4-HNE adduct formation, reflecting reduced oxidative damage. SS-31, in contrast, more effectively preserved mitochondrial structural integrity. Both compounds attenuated inflammation by suppressing NF-?B and NLRP3 activation. They also improved insulin sensitivity by increasing p-Akt and GLUT2 expression. Histological analysis using H&E staining revealed marked reductions in hepatic steatosis. Mitochondrial dysfunction drives MASLD progression. In aged MASLD mice, MitoQ enhances antioxidant defense, SS-31 preserves integrity, and both improve insulin signaling and reduce fibrosis, supporting mitochondrial therapy for MASLD.
Cell Biochem Funct. 2026 Sep;44(9): e70298

Dual miRNA-Mediated Axes Act in Concert in the Antioxidant Action of Eicosapentaenoic Acid: let-7c-3p/TFAM Drives Mitochondrial Biogenesis While miR-34c-5p/SIRT1 Potentiates Enzymatic Defenses.

Haiqi Wang, Yanqi Lin, Yuanyuan Li, Xiaowen Wu, Jingyu Lin, Shiying Huang, Guiling Li.

  Previous transcriptomic analysis revealed that eicosapentaenoic acid (EPA) alters miRNA expression in HepG2 cells. Two key miRNA-mRNA axes mediating EPA's antioxidant effects were identified. EPA was found to downregulate let-7c-3p, which directly targets mitochondrial transcription factor A (TFAM). Inhibiting let-7c-3p or overexpressing TFAM enhanced antioxidant capacity, reduced reactive oxygen species, improved mitochondrial function, and promoted mitochondrial biogenesis. In parallel, EPA was found to upregulate miR-34c-5p, which directly targets NAD-Dependent Protein Deacetylase Sirtuin (SIRT1). This repression of SIRT1 is associated with increased activities of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. These findings indicate a dual-miRNA mechanism through which EPA alleviates oxidative stress via coordinated enhancement of mitochondrial biogenesis and enzymatic defenses.

Keywords:  SIRT1; TFAM; antioxidant defense; eicosapentaenoic acid; microRNA; mitochondrial function

DOI:  https://doi.org/10.1002/cbf.70298
BMJ Open Diabetes Res Care. 2026 Sep 07. pii: e005990. [Epub ahead of print]14(5):

Reproductive lifespan in relation to diabetes mellitus and metabolic syndrome in a nationally representative population.

AJin Cho, Yun Soo Hong, Hoon Kim.

   AIMS: The association between reproductive lifespan (RLS) and diabetes and metabolic syndrome in menopausal women remains unclear. We investigated whether a short RLS is associated with diabetes and metabolic syndrome using nationally representative US data.
METHODS: We conducted a cross-sectional analysis of menopausal women using data from the US National Health and Nutrition Examination Survey from 2007 to 2018. Weighted logistic regression models accounting for the complex survey design were used to estimate ORs and 95% CIs for diabetes and metabolic syndrome across quartiles of RLS.
RESULTS: A total of 868 postmenopausal women with a mean age of 54.1 years were included. The mean ages at menarche and menopause were 12.7 and 51.2 years, respectively. The mean RLS was 38.5 years and was categorized into quartiles (11-35, 36-39, 40-42 (reference group), and 43-50 years). Compared with the reference group, women in the second quartile had higher odds of diabetes (OR 2.23; 95% CI 1.05 to 4.73) after adjustment for age, demographic characteristics, behavioral factors, age at menarche, and family history of diabetes. In contrast, women in the shortest RLS quartile were not at increased odds of diabetes, and no significant linear trend was observed across RLS categories. No robust association was observed between RLS and metabolic syndrome. These findings were consistent in sensitivity analyses that additionally included women with surgical menopause and that further adjusted for dietary factors.
CONCLUSION: A relatively short RLS may be associated with higher odds of diabetes, although this association did not follow a clear dose-response pattern. These findings suggest that reduced lifetime estrogen exposure may contribute to cardiometabolic risk. Given the cross-sectional design, longitudinal studies are needed to support these findings.

Keywords:  Menopause; Metabolic Syndrome

DOI:  https://doi.org/10.1136/bmjdrc-2026-005990
Diabetes Metab J. 2026 Sep;50(5): 825-843

Mitochondrial Proteostasis Links Diabetes and Sarcopenia: Cross-Scale Convergence from Experimental Models to Human Multi-Omics.

Shibo Wei, Soyeon Shin, Dongryeol Ryu, Chang-Myung Oh.

  Sarcopenia in type 2 diabetes mellitus is increasingly recognized as a mechanistic consequence of chronic metabolic stress rather than mere age-related comorbidity. This review synthesizes evidence demonstrating how insulin resistance, hyperglycemia, lipotoxicity, and inflammation converge on skeletal muscle mitochondrial proteostasis to drive progressive decline. We evaluate seven pathway modules-mitochondrial dynamics, mitophagy, biogenesis, oxidative phosphorylation, nicotinamide adenine dinucleotide (NAD+)/sirtuin (SIRT)-linked regulation, protein import, and the mitochondrial unfolded protein response (UPRmt)-across an evidence map encompassing basic, clinical, and multi-omics studies. Dynamics and mitophagy represent mechanistically central quality-control nodes; their impairment permits dysfunctional organelle accumulation and promotes atrophic cascades. Direct evidence density, however, remains weighted toward oxidative phosphorylation and mitochondrial biogenesis. NAD+/SIRT-linked regulation, protein import fidelity, and UPRmt represent mechanistically upstream but comparatively underinvestigated signals. We propose a diabetes-centered framework where mitochondrial proteostasis failure mediates atrophy and reinforces insulin resistance via a self-amplifying feed-forward loop, supported by pathway responsiveness to coherent interventions. Human multi-omics data highlight network-level dysregulation rather than isolated defects, underscoring module-based biomarker strategies. Translationally, exercise remains the mechanistic cornerstone, while pathway-directed adjuncts-NAD+ precursor repletion, mitophagy modulators, and emerging pharmacotherapeutics-are warranted for patients with identifiable module-specific failure patterns.

Keywords:  Diabetes mellitus, type 2; Mitophagy; Multiomics; Muscle, skeletal; Proteostasis; Sarcopenia

DOI:  https://doi.org/10.4093/dmj.2026.0310
Sci Rep. 2026 Aug 14. pii: 28221. [Epub ahead of print]16(1):

Targeting TWEAK to enhance mitochondrial biogenesis and attenuate age-related muscle mass loss.

Zhuoya Maimaitiwusiman, Saiyare Xuekelati, Anyan Wang, Nadila Airiken, Yanbin Xu, Shuke Guo, Yining Yang, Hongmei Wang.

  Mitochondrial dysfunction is an important cause of sarcopenia, and TWEAK/Fn14, as one of the major muscle wasting cytokines, its role in the development of sarcopenia by regulating mitochondrial biogenesis remains unclear. Expression of TWEAK in old and young mice was both detected. TWEAK was silenced in C2C12 myocytes using lentiviral vectors. Immunofluorescence, western blot, real-time polymerase chain reaction (RT-PCR), and ELISA were enrolled to analyze the effects of TWEAK on myotube size, mitochondrial content, mitochondrial ROS, and inflammatory factors. Additionally, aged mice received two injections of AAV9 vectors at 15 and 17 months of age. Upon reaching 18 months of age, the effects of TWEAK knockdown on grip strength, muscle mass, and gastrocnemius muscle indices were evaluated. TWEAK/Fn14 expression was significantly increased in old mice (p < 0.001). Compared with young controls, old mice exhibited a significant decrease in grip strength (p < 0.001) and a significant increase in lean mass (p < 0.05), whereas no significant difference was observed in fat content. In DEX-treated C2C12 myotubes, TWEAK knockdown significantly increased myotube diameter, enhanced ATP content and mitochondrial quantity, upregulated protein expression of SIRT1, PGC-1α, and p-AMPK, and inhibited mitochondrial ROS, Ca2+ levels, p-p38 expression, and the secretion of inflammatory cytokines (TNF-α, IL-1β, IL-6, and iNOS). In aged mice, TWEAK knockdown did not significantly alter forelimb grip strength or lean mass, but significantly increased fat mass (p < 0.05). Mechanistically, TWEAK knockdown promoted AMPK signaling, inhibited p38 MAPK activation, enhanced mitochondrial biogenesis, and reduced serum levels of IL-1β, IL-6, and iNOS (p < 0.05), whereas serum TNF-α levels showed no significant difference. TWEAK knockdown attenuates age-related skeletal muscle mass loss and improves mitochondrial biogenesis in skeletal muscle, accompanied by modulated inflammatory factor release and altered AMPK-p38 MAPK signaling activity. However, no significant improvement in forelimb grip strength was observed in the in vivo experiment. These findings indicate that TWEAK suppression may represent a promising strategy for preserving muscle mass and metabolic homeostasis during aging, though its capacity to fully restore functional capacity requires further investigation.

Keywords:  Atrophy; Fn14; Gastrocnemius; Mitochondria; TWEAK

DOI:  https://doi.org/10.1038/s41598-026-64401-2
Food Sci Nutr. 2026 Sep;14(9): e72324

Epigallocatechin Gallate From Tea Delays Oocyte Aging After Ovulation in Mice.

Jing Lin, Hua-Chao Gao, Li-Jun Li, Miao Hu, Li-Fan Guo, Hong-Yan Guo, Xiao-Wen Jin, Peng Xu, Zhao-Jia Ge, Lei Zhao.

  In clinic, once the ovulated oocytes cannot be fertilized timely, they begin to undergo post-ovulatory aging, which impacts the embryo development and offspring health. Until now, there are no better methods to delay post-ovulatory oocyte aging. Epigallocatechin gallate (EGCG) is the most abundant bioactive component of tea polyphenols that are beneficial for alleviating the deleterious influence of environmental factors on oocyte quality. In the present study, we examined the role of EGCG in delaying oocyte aging after ovulation in vitro. Ovulated oocytes were treated with EGCG at different concentrations, and the fragmentation rate, induced by aging, was significantly reduced by EGCG at 50 μM in vitro. To further elucidate the influence of EGCG on the quality of post-ovulatory aged oocytes, we examined the spindle morphology of aged oocytes. The results showed that EGCG significantly decreased the abnormal rate of spindle morphology in post-ovulatory aged oocytes. The high level of reactive oxygen species (ROS) and mitochondrial dysfunction in post-ovulatory aged oocytes were also improved by EGCG, which might be a reason for the reduced apoptosis. The reduced sperm binding capacity of aged oocytes was increased by the addition of EGCG. These suggest that EGCG can improve the quality of post-ovulatory aged oocytes.

Keywords:  EGCG; oocyte; postovulatory aging; tea

DOI:  https://doi.org/10.1002/fsn3.72324
JAMA Intern Med. 2026 Sep 08.

Menopausal Hormone Therapy and Cardiovascular Risk in Midlife Women With Vasomotor Symptoms.

Ziyuan Wang, Sonja A Swanson, Maria M Brooks, Emma Barinas-Mitchell, Marnie Bertolet, Jared W Magnani, Rebecca C Thurston, Samar R El Khoudary.

Importance: Vasomotor symptoms in perimenopause are associated with increased future cardiovascular (CVD) risk. Most clinical trials on menopausal hormone therapy (MHT) and CVD risk have focused on postmenopausal women, with limited study of the perimenopausal period when hormonal fluctuations and symptoms are greatest. Moreover, these trials were not designed to evaluate CVD risk with MHT among women with vasomotor symptoms.
Objective: To estimate the effect of MHT on CVD risk among perimenopausal and recently postmenopausal women with vasomotor symptoms and assess the extent to which timing of MHT use relative to menopause and race and ethnicity modify this effect.
Design, Setting, and Participants: Cohort data from the Study of Women's Health Across the Nation (SWAN, 1997-2017)-a multiethnic, multicenter, longitudinal study of the menopause transition-were used to emulate a sequence of target trials. Eligible participants were women who self-reported any vasomotor symptoms (ie, hot flashes and/or night sweats over the past 2 weeks) and who were CVD-free, with no prior MHT use. Data were analyzed from January 2023 to December 2025.
Exposure: MHT use (systemic estrogen with/without progestogens, verified from medication containers).
Main Outcomes and Measures: CVD events (myocardial infarction, stroke, heart failure, and revascularization) were self-reported. CVD-related death was recorded from death certificates.
Results: Of 2737 women who reported any vasomotor symptoms, 755 initiated MHT (mean [SD] age, 53.7 [4.6] years) over the 20-year follow-up period, during which 224 fatal and nonfatal CVD events occurred. Overall, the estimated adjusted hazard ratio (aHR) of CVD events for MHT initiation vs noninitiation was 0.78 (95% CI, 0.62-0.98). The estimated aHR was 0.73 (95% CI, 0.58-0.93) and 1.53 (95% CI, 0.66-3.52) among women initiating MHT 10 or fewer years vs more than 10 years from the onset of menopause, respectively (P value for interaction: .02). Race and ethnicity modified the MHT initiation effect, with Black women showing protective effect (aHR, 0.51; 95% CI, 0.33-0.81), while no clear effects were observed in White women or women of other races (P value for interaction = .007).
Conclusions and Relevance: The presented results are pooled from all target trials and found that MHT initiation during perimenopause or recently postmenopausal women with vasomotor symptoms was estimated to reduce CVD risk by 22%. Benefits were more pronounced in Black women and women who initiated MHT within 10 years of menopause onset. However, all estimates warrant caution given the potential for residual confounding. Given the inconsistency of the cardiovascular benefits and the need to consider overall risk-benefit balance, these findings should not be used to support MHT for CVD prevention.

DOI: https://doi.org/10.1001/jamainternmed.2026.2922
J Menopausal Med. 2026 Aug;32(2): 65-74

Menopausal Hormone Treatment as a Preventive against the Progress of Chronic Diseases in Menopausal Women.

Jae Yeon Woo, Frederick Nicholas Naftolin.

  This review aimed to summarize the biological rationale for the protective effects of estrogen, the robust evidence supporting the benefits of menopausal hormone therapy (MHT), and the evolving regulatory and historical context shaped by the reinterpretation of the Women's Health Initiative data. This study outlines the risk-benefit profile of contemporary MHT regimens and presented a modern clinical framework for the use of MHT as a preventive strategy to support metabolic, cardiovascular, and skeletal health across and beyond the menopausal transition. Moreover, this review emphasized that menopausal symptoms should be recognized as a critical biological inflection point necessitating proactive intervention. Furthermore, the 2025 FDA regulatory shift reinforces the safety and efficacy of individualized MHT when initiated within the "window of opportunity," providing a definitive strategy for long-term prevention of chronic diseases in healthy women.

Keywords:  Drug labeling; Estradiol; Estrogens; Hormones; Menopause

DOI:  https://doi.org/10.6118/jmm.26001
Front Cell Dev Biol. 2026 ;14 1926968

β-Hydroxybutyrate-induced mitochondrial dysfunction and oxidative stress in BMSCs are ameliorated by mitophagy activation.

Tao Tang, Jing Zhou, Xianbo Jia, Jiahao Shao, Meigui Wang, Siqi Xia, Shuai Chen, Wenqiang Sun, Jie Wang, Songjia Lai.

  Ketosis is a common metabolic disorder in periparturient dairy cows and is characterized by elevated circulating BHBA concentrations. Although the effects of ketosis on hepatic metabolism have been extensively studied, its impact on skeletal muscle remains poorly understood. This study investigated the effects of BHBA on bovine muscle satellite cells (BMSCs) and the role of mitochondrial quality control in BHBA-induced cellular injury. BHBA treatment significantly inhibited BMSC proliferation, promoted apoptosis, increased intracellular and mitochondrial ROS accumulation, reduced antioxidant enzyme activities, and impaired mitochondrial membrane potential in a dose-dependent manner. BHBA also disrupted mitochondrial ultrastructure, altered the expression of mitochondrial respiratory chain genes, promoted mitochondrial fission, and suppressed mitophagy. Similar effects were observed in C2C12 myoblasts, indicating that the detrimental effects of BHBA on myogenic cells are conserved across different cellular models. Notably, activation of mitophagy alleviated BHBA-induced oxidative stress, reduced ROS accumulation, improved antioxidant capacity, and enhanced ketone body metabolism, whereas inhibition of mitophagy exacerbated these alterations. These findings demonstrate that BHBA directly induces oxidative damage and mitochondrial dysfunction in myogenic cells. Impaired mitophagy contributes to the progression of cellular injury, whereas enhancement of mitochondrial quality control confers protection. This study provides new insights into the cellular mechanisms underlying skeletal muscle metabolic dysfunction during bovine ketosis and identifies mitophagy as a potential therapeutic target.

Keywords:  ROS; ketone body metabolism; ketosis cow; mitochondrial function; skeletal muscle

DOI:  https://doi.org/10.3389/fcell.2026.1926968
Mater Horiz. 2026 Sep 08.

Bioinspired plant-derived extracellular vesicles enabling dual-targeting therapy for primary ovarian insufficiency.

Yaoqin Mu, Xinyi Zhang, Keyi Ye, Qiuyue Liao, Wei Yang, Jun Dai, Fan Xia, Kezhen Li.

Extracellular vesicles (EVs) have emerged as promising therapeutic agents for restoring ovarian function and fertility in chemotherapy-induced premature ovarian insufficiency (POI). However, their limited ovarian targeting capacity and inefficient mitochondrial delivery have substantially constrained their therapeutic efficacy. Here, we present a biomimetic, dual-targeted EV platform derived from Lycium barbarum (TPP-GCM-LBEVs) and demonstrate its therapeutic potential in a mouse POI model. Hybridization with granulosa cell membranes (GCMs) confers intrinsic ovarian-homing capability, whereas subsequent surface conjugation with triphenylphosphonium (TPP) promotes mitochondrial targeting following cellular uptake. TPP-GCM-LBEVs efficiently target granulosa cells and their mitochondria in vitro and in vivo, with cellular internalization mediated predominantly by caveolae- and lipid-raft-dependent endocytosis. Subsequently, TPP-GCM-LBEVs restore mitochondrial ultrastructure and bioenergetic function in granulosa cells, thereby re-establishing ovarian redox and metabolic homeostasis. This mitochondrial rescue enhances the paracrine metabolic support provided to oocytes, thereby improving oocyte quality and developmental competence. Consistent with these effects, treatment with TPP-GCM-LBEVs rescues follicular development, ovarian endocrine function, and natural fertility in POI mice. Collectively, this cross-species, dual-targeted, plant-derived EV strategy provides a translatable and effective therapeutic framework for POI, with broader implications for mitochondria-associated reproductive ageing.

DOI: https://doi.org/10.1039/d6mh01330a
Nutr Rev. 2026 Sep 10. pii: nuag109. [Epub ahead of print]

Effects of Vitamin D Supplemental Dose in Adults with Prediabetes: A Systematic Review and Network Meta-Analysis.

Wenxuan Wu, Yanyang Han, Jingxin Yang, Huidi Zhang, Yuting Li, Yining Sun, Yichun Hu, Lichen Yang.

   CONTEXT: It is evident that the supplementation of vitamin D has been identified as a potential intervention strategy with the objective of reducing the incidence of type 2 diabetes (T2D). However, the optimal dosage of vitamin D supplementation to improve prediabetes in intervention studies remains to be elucidated.
OBJECTIVE: The objective of this study was to evaluate the effects vitamin D supplement dose in adults with prediabetes, by conducting a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs).
DATA SOURCES: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to March 2025.
DATA EXTRACTION: An NMA of multiple doses, including low (LDS) (<1000 IU d-1), medium (MDS) (1000-2000 IU d-1), high (HDS) (2000-4000 IU d-1), and extremely high (EHDS) (≥4000 IU d-1) dosing strategies, was conducted.
DATA ANALYSIS: Our NMA of 21 RCTs suggested that, compared with control, LDS decreased fasting blood glucose (FBG) and was ranked as the most effective in decreasing FBG (surface under the cumulative ranking curve = 87.9%). In terms of decreasing fasting insulin (FIN) level, EHDS (mean difference [MD] = -0.30; 95% CI -0.56 to -0.03) was more effective than control. And EHDS (MD = -2.82; 95% CI, -5.06 to -0.57) was more efficacious than LDS in reducing the homeostasis model assessment for insulin resistance (HOMA-IR) value. The EHDS was the top-ranked strategy in reducing FIN, HOMA-IR, HOMA of β-cell function, 2-h postload glucose, and new-onset T2D, and for improving normal glucose regulation.
CONCLUSION: The findings suggest that vitamin D supplementation at different doses in adults with prediabetes may improve glycemic parameters in different dimensions. However, there are few low-dose studies, and more high-quality studies are needed to confirm this.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD420251108418.

Keywords:  glycemic control; network meta-analysis; prediabetes; vitamin D supplementation

DOI:  https://doi.org/10.1093/nutrit/nuag109
Front Nutr. 2026 ;13 1888269

Ergothioneine, collagen peptides, and sodium hyaluronate ameliorate facial skin aging via modulating oxidative stress, inflammation, and extracellular matrix homeostasis.

Zhiqing Zhou, Lingling Zhao, Lei Chen, Xuanxiang Zhao, Xinwei Li, Xuying Luo, Bin Zhang, Jianyin Miao, Feitong Liu.

   Background: Skin aging involves intrinsic chronological aging and extrinsic photoaging, characterized by impaired barrier function, extracellular matrix (ECM) degradation, and chronic inflammation.
Methods: This study evaluated anti-aging efficacy and mechanisms of ergothioneine (EGT), collagen peptides (CP) and sodium hyaluronate (NaHA) using an ex vivo human skin model and a clinical trial.
Results: Ex vivo results showed that the EGT+CP+NaHA triple combination (TC) attenuated UV-induced epithelial thinning and collagen fiber disruption. Mechanistically, TC enhanced antioxidant capacity by up-regulating Nrf2 and SOD2 expression, modulated the senescence-associated secretory phenotype (SASP) via restoring TGF-β1 and suppressing IL-1α, IL-6, and MMP1 levels, and preserved ECM integrity by reversing reductions in collagen I, III, IV, VII, XVII, and hyaluronic acid (HA) contents. Clinically, oral TC to Chinese women improved skin hydration, elasticity, and barrier function, while reducing the number, depth, area, and volume of crow's feet wrinkles, nasolabial folds and marionette lines.
Conclusion: These findings demonstrate that TC exerts multifaceted anti-aging effects by targeting oxidative stress, inflammatory pathways, and ECM homeostasis, providing a scientific basis for the development of novel oral nutricosmetics for facial skin anti-aging.

Keywords:  anti-aging; collagen peptides; ergothioneine; extracellular matrix homeostasis; facial skin aging; oral nutricosmetic; oxidative stress; sodium hyaluronate

DOI:  https://doi.org/10.3389/fnut.2026.1888269
Cardiovasc Hematol Disord Drug Targets. 2026 Aug 29.

The Silent Vascular Shift: Endothelial Dysfunction and Cardiovascular Risk in Menopausal Women.

Arti Saini, Inderjeet Verma, Ruby Bhatia.

   BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death among women worldwide, with the risk significantly increasing after menopause. Hormonal changes during menopause influence the pathophysiology of endothelial dysfunction and atherosclerosis. Lowering levels of estrogen causes vascular hardening, decreased nitric oxide bioavailability, and a sharpened inflammatory response, which may contribute to increased cardiovascular risk during middle life in women. To review the role of endothelial health in cardiovascular risk among postmenopausal women, discuss the underlying mechanisms, and explore current management strategies aimed at reducing the incidence and impact of coronary artery disease.
METHODS: A comprehensive literature search via PubMed, Scopus, and Web of Science (2015-- 2025) via search strings (menopause OR perimenopause OR postmenopause) AND (endothelial dysfunction OR endothelial function OR nitric oxide OR vascular inflammation) AND (cardiovascular disease OR atherosclerosis OR cardiovascular risk) was conducted, with a focus on large epidemiological cohorts, randomized controlled trials, and mechanistic studies.
RESULTS: Postmenopausal women have a higher risk of developing CVD, and they have comparatively deteriorated endothelial dysfunction.
DISCUSSION: Compared with men, women experience unique changes in lipid profiles, metabolic syndrome, and fat distribution during and after menopause, which increase their cardiovascular risk. Traditional risk factors, such as hypertension, diabetes, smoking, physical inactivity, and obesity, also affect women differently. Hormonal changes during menopause further influence the pathophysiology of endothelial dysfunction and atherosclerosis. Lifestyle interventions, such as structured exercise, show promise for reducing risk, but evidence supporting the use of phytoestrogens and nutraceuticals is limited and heterogeneous.
CONCLUSION: Menopause is a high-risk critical phase of increased cardiovascular risk through endothelial dysfunction. Multifaceted prevention measures, such as primary early intervention and individualized responses, are necessary to minimize long-term morbidity and mortality.

Keywords:  Postmenopausal; cardiovascular risk; coronary vascular disease; endothelial dysfunction; quality of life; transition period; treatment

DOI:  https://doi.org/10.2174/011871529X448903260820091109
Front Immunol. 2026 ;17 1917296

Mitochondrial homeostasis and aging: the mtDNA-cGAS-STING axis.

Ling Wang, Zhengwei Zhang, Binbin Xia, Jun Li, Hongmei You.

  Aging and its associated diseases have become an increasingly severe global health challenge, not only significantly exacerbating the global disease burden but also posing a continuous threat to public health systems worldwide. During the aging process, the aberrant release of endogenous mitochondrial DNA (mtDNA) is a key trigger for the activation of the cGAS-STING innate immune pathway. Existing research has confirmed that the overactivation of the cGAS-STING pathway is the core molecular mechanism driving the senescence-associated secretory phenotype (SASP), chronic inflammation, and organ functional decline. Notably, the mechanisms of mtDNA release and the activation characteristics of the cGAS-STING pathway exhibit significant organ-specificity. Different tissues mediate mtDNA leakage through specific pathways, such as mitochondrial permeability transition, oxidative damage, and defective mitophagy, thereby differentially regulating downstream inflammatory signals. Given the central driving role of the aberrantly activated mtDNA-cGAS-STING axis in age-related organ damage, targeting this pathway has emerged as a promising therapeutic strategy for the systemic mitigation of aging-associated chronic inflammation. This review systematically elucidates the molecular basis of the mtDNA-cGAS-STING pathway, delves into its organ-specific activation mechanisms, and critically evaluates current intervention frameworks and clinical prospects, aiming to provide a theoretical basis and innovative perspectives for the precision prevention and clinical management of age-related diseases.

Keywords:  aging; cGAS-STING; immunity; mitochondria; mtDNA

DOI:  https://doi.org/10.3389/fimmu.2026.1917296