bims-mistre 2026-05-24 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2026–05–24
twenty-six papers selected by
Ellen Siobhan Mitchell, MitoQ

Gdf15 expression in thermogenic adipocytes regulates diet-induced weight gain in a sex-dependent manner.
Review article: Improving Mitochondrial Function: Current Therapeutic Perspectives in Neurodegenerative Diseases.
Plasma proteomics link menopause timing to brain aging and dementia risk.
Mitochondrial Function in Neurons and Glia in Health and Its Alteration in Parkinson's Disease: A Review.
A New Food Supplement Product Containing Ergothioneine Protects Against Cyclophosphamide-Induced Primary Ovarian Insufficiency in Rats.
Stevioside extends the healthspan and improves Alzheimer's disease and increases oxidative stress resistance via the mitochondrial unfolded protein response.
Mitochondria and polycystic ovary syndrome: The role of ferroptosis, inflammasomes, and endoplasmic reticulum stress.
A mechanistic digital twin of ovarian aging integrating follicular dynamics, mitochondrial decline, and lifestyle perturbations.
Creatine monohydrate for lean mass, strength, and bone density in postmenopausal women: a systematic review and meta-analysis.
17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.
Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals.
Age at menopause and risk of sarcopenia in postmenopausal women: evidence from the China health and retirement longitudinal study.
Mitochondrial Dysfunction in MASLD: Evidence in Dietary Models and Potential Therapeutic Interventions.
Effect of mitochondrial dysfunction on scar formation after spinal cord injury.
Mitochondrial Dysfunction Contributes to Endothelial Damage in Metabolic Diseases: Role of Mitochondrial DNA in Inflammation.
Legacy of Tehran Lipid and Glucose Study; Evidence on Reproductive Lifespan and Cardiometabolic Health.
Mitoredox Shifts in Mitochondrial Dysfunction.
Fisetin Supplementation Attenuates Premature Vascular Aging Induced by Doxorubicin via Suppression of Cellular Senescence and Mitochondrial Oxidative Stress.
Mitochondrial respiratory capacity in kidney podocytes is high, age-dependent, and sexually dimorphic.
Reversing diastolic dysfunction in diabetes: a mitochondrial quality control-centric pharmacological approach.
GDF15 predisposes aortic dissection through regulation of vascular smooth muscle cell proliferation and phenotypic change via the ERK/Akt pathway.
Effect of Green Tea Extract Supplementation on Substrate Utilization: A GRADE-Assessed Systematic Review and Dose-Response Meta Analysis of Randomized Controlled Trials.
Soluble Fiber Intake Restores the Estrous Cycle and Sex Hormone Alterations in APP/PS1 Female Mice.
Fucoxanthin improves stomatitis by regulating mitochondrial function and cGAS-STING signaling.
Breathing slower is not always better: Slow-paced breathing enhances heart rate variability but produces age-differential effects on emotional reactivity and memory.
Alkaloids from Dendrobium Nobile Lindl Improves Mitochondrial Function by Enhancing the Activity of v-ATPase in APP/PS1 Mice.

Mol Med. 2026 May 18.

Gdf15 expression in thermogenic adipocytes regulates diet-induced weight gain in a sex-dependent manner.

Jayashree Jena, Ayushi Sood, Joshua Peterson, Luis Miguel García-Peña, Eric T Weatherford, Pritesh Patel, Shelly Roitershtein, David A Smith, Vamsi Challa, Randy J Seeley, Renata O Pereira.

   BACKGROUND: Growth differentiation factor 15 (GDF15) is a stress-induced cytokine known to bind to its endogenous receptor GDNF-family α-like (GFRAL) in the hindbrain, thereby modulating energy homeostasis. In response to prolonged high-fat diet (HFD) feeding, Gdf15 expression is induced in various tissues, including liver and brown adipose tissue (BAT), leading to increased GDF15 serum levels. Although the liver is the primary source of circulating GDF15 during diet-induced obesity (DIO), other tissues are also required. We investigated whether BAT contributes to GDF15 circulating levels and if GDF15 induction in BAT regulates systemic metabolism during DIO.
METHODS: We generated mice with selective Gdf15 deletion in thermogenic adipocytes (KO) and subjected them to 12 weeks of HFD feeding to determine the role of BAT-derived GDF15 on systemic metabolic homeostasis in both male and female mice.
RESULTS: Unexpectedely, despite no changes in GDF15 serum levels in mice fed ad-libitum regardless of sex or genotype, female KO mice were resistant to DIO, had increased energy expenditure and improved mitochondrial fatty acid oxidation in BAT, which was prevented by ovariectomy. Conversely, male KO mice had increased body weight and adiposity upon HFD feeding, along with reduced respiratory capacity in BAT mitchondria, and increased markers of fibro-inflammation.
CONCLUSIONS: Together, our data reveal GDF15 induction in BAT is required to regulate weight gain in mice in a sex-dependent manner. Our results also suggest female sex hormones contribute to increase energy expenditure in female KO mice promoting leanness. Our study underscore the importance of rigorously addressing sex differences in GDF15 biology and pharmacology and suggests GDF15 might exert effects on energy balance and adiposity that are independent of signaling through GFRAL.

Keywords:  Brown adipose tissue; GDF15; Obesity; Sex dimorphism

DOI:  https://doi.org/10.1186/s10020-026-01505-5
Pharmacol Res. 2026 May 18. pii: S1043-6618(26)00142-8. [Epub ahead of print] 108227

Review article: Improving Mitochondrial Function: Current Therapeutic Perspectives in Neurodegenerative Diseases.

Julia Brechtel, Christine Lietz, Selin Akpinar Adscheid, Kristina Friedland.

  Mitochondrial dysfunction is considered one of the key drivers of neurodegeneration and pathological aging, characterized by impaired energy production, oxidative stress, disrupted mitophagy, and biogenesis. Because mitochondria regulate bioenergetics, redox balance, and neuronal survival, therapeutic strategies that restore mitochondrial integrity are of growing interest. This review outlines mechanisms of mitochondrial function and failure, links them to Alzheimer's and Parkinson's disease, and summarizes evidence on phytochemicals and mitochondria-targeted small molecules, which enhance biogenesis, mitophagy, respiratory efficiency, and antioxidant defence in preclinical models together with life-style interventions. Although many compounds demonstrate preventive rather than restorative benefit and clinical evidence remains limited, next-generation approaches, including nanoparticles for mitochondrial delivery, mtDNA editing, and mitochondrial transfer, suggest increasing therapeutic potential. We underline that future success will rely on improved delivery, synergistic combinations, and rigorous clinical trials. Mitochondria-directed therapies may ultimately provide disease-modifying or preventive strategies for neurodegenerative disorders.

Keywords:  Alzheimer’s Disease; Mitochondria-Targeted Therapies; Mitochondrial Dynamics; Mitochondrial Dysfunction; Parkinson’s Disease; Phytochemicals; Small Molecule

DOI:  https://doi.org/10.1016/j.phrs.2026.108227
Res Sq. 2026 May 04. pii: rs.3.rs-9499814. [Epub ahead of print]

Plasma proteomics link menopause timing to brain aging and dementia risk.

Madeline Wood Alexander, Brendan Wood, Hamilton Oh, Veronica Bot, Julia Borger, Francesca Galbiati, Keenan Walker, Susan Resnick, Heather Ochs-Balcom, Tony Wyss-Coray, Charles Kooperberg, Alex Reiner, Emily Jacobs, Jennifer Rabin, Kaitlin Casaletto, Rowan Saloner.

Earlier menopause is a risk factor for several age-related diseases, including dementia. The biological pathways linking menopause timing to later-life brain aging are not understood. Leveraging large-scale plasma proteomics in postmenopausal women from the UK Biobank (N=15,012), earlier menopause was associated with upregulation of pro-inflammatory and extracellular matrix degradation pathways, plus accelerated aging across proteomic clocks of organ and cellular aging, including brain and oligodendrocyte aging. Elevated GDF15, a canonical aging marker, was the top protein correlate of earlier menopause. We observed robust replication of menopause timing proteomic shifts in the Women's Health Initiative Long Life Study (N=1,210). In UKB, proteins associated with earlier menopause, including GDF15, exhibited concordant associations with incident dementia risk and brain atrophy, cerebral small vessel disease burden, and white matter microstructural integrity. Collectively, our findings identify proteomic signatures linking ovarian aging to brain aging, providing a framework to inform interventions to reduce dementia risk.

DOI: https://doi.org/10.21203/rs.3.rs-9499814/v1
Curr Neuropharmacol. 2026 May 15.

Mitochondrial Function in Neurons and Glia in Health and Its Alteration in Parkinson's Disease: A Review.

Monika Kaushik, Mrugendra Potdar, Prathap Madeswaraguptha, Murugesan Vanangamudi, Md Abubakar, Manoj Kumar Mishra, Sachchida Nand Rai.

   INTRODUCTION: Mitochondria play an important role in maintaining redox balance, energy, calcium, and the viability of neurons. The mitochondrial dysfunction is one of the primary sources of glial activation and dopaminergic neuron loss in Parkinson's disease (PD). The key biochemical elements of the pathogenesis of PD include impaired oxidative phosphorylation, elevated generation of reactive oxygen species (ROS), and impaired mitophagy.
METHODS: This review is a synthesis and stringent evaluation of recent experimental, clinical and genetic studies relating mitochondrial dysfunction and Parkinson's disease (PD). We examined information on bioenergetics, mitochondrial dynamics, calcium homeostasis, and interactions between neurons and glia. The molecular and therapeutic importance of therapies, such as mitophagy modulators, bioenergetic enhancers, and mitochondrial antioxidants, was investigated. The absence of Complex I, excess ROS, mitochondrial DNA damage, and nonfunctioning fusionfission cycles leads to neurodegeneration. The glial metabolic abnormalities worsen the oxidative stress and neuroinflammation, weakening the support of the neurons. The effects of impaired mitophagy are the accumulation of dysfunctional mitochondria, and the effects of calcium overload disrupt energy metabolism. Neuroprotective effects of such substances as spermidine, urolithin A, resveratrol, αlipoic acid, MitoQ, SkQ1, or CoQ10 have been shown using preclinical research. Sacrifices such as exercising and proper dieting enable the mitochondria to perform better and become stronger.
DISCUSSION: Mitochondrial dysfunction enhances the progression of PD through oxidative stress, bioenergetic breakdown, and inflammatory signalling. Attention to these related systems is an entire way to alter the direction of a disease.
CONCLUSION: PD can be treated using an increase in mitochondrial quality control, redox regulation, and metabolic efficiency. Continued studies in the framework of precision medicine are required to validate the safety and effectiveness of mitochondrial-targeted medications.

Keywords:  Astrocytes; Parkinson’s disease; calcium ions; free fatty acid oxidation; glycolysis; microglia; mitochondria; neuroinflammation; neurons; oligodendrocytes; oxidative stress

DOI:  https://doi.org/10.2174/011570159X415585260303184042
Mol Nutr Food Res. 2026 May;70(10): e70509

A New Food Supplement Product Containing Ergothioneine Protects Against Cyclophosphamide-Induced Primary Ovarian Insufficiency in Rats.

Chen Jin, Minyan Shi, Han Liu, Siling He, Huawei Zhu, Pan Wang.

Primary ovarian insufficiency (POI) is characterized by disrupted estrous cycles, impaired folliculogenesis, oxidative stress, and inflammation. In this study, a cyclophosphamide (CTX)-induced POI rat model was used to evaluate the protective effects of a nutraceutical formula (including ergothioneine, Coenzyme Q10, pyrroloquinoline quinone, hydroxytyrosol, and vitamin E) at different doses. CTX markedly prolonged the estrous cycle, reduced estrus duration, decreased ovarian weight, impaired follicular development, and elevated granulosa cell apoptosis. CTX induced oxidative stress, as evidenced by reduced catalase (CAT), superoxide dismutase (SOD) activity, and glutathione (GSH) content, alongside increased malondialdehyde (MDA) in ovarian tissue. Interventions with the product restored estrous cyclicity, increased ovarian weight, improved primordial follicle counts, and reduced atretic follicles and granulosa cell apoptosis. Hormonal balance was partially normalized, with increased E2 and AMH and reduced LH and FSH levels. Oxidative stress markers improved significantly, with higher CAT, SOD, and GSH levels and reduced MDA concentrations. Inflammatory cytokine analysis revealed that EGT and the low-dose product reduced TNF-α, IL-6, and IL-1β in skin tissue. These findings suggest that the nutraceutical formula confers multi-targeted protection against CTX-induced POI with improved ovarian function, decreased oxidative stress in the ovary, and increased the expression of genes involved in mitochondrial biogenesis.

DOI: https://doi.org/10.1002/mnfr.70509
Food Funct. 2026 May 15.

Stevioside extends the healthspan and improves Alzheimer's disease and increases oxidative stress resistance via the mitochondrial unfolded protein response.

Xiaocong Li, Yi Xiao, Fang Liu.

Increased evidence suggests that moderate activation of the mitochondrial unfolded protein response (UPRmt) can delay aging and ameliorate neurodegenerative pathologies. Stevioside (Ste), a natural zero-calorie sweetener extracted from Stevia rebaudiana, has gained global acceptance as a sugar substitute in the food industry. Accumulated studies indicate that stevioside exhibits a wide spectrum of biological effects, including anti-hyperglycemic, anti-hypertensive, anti-inflammatory, and antimicrobial activities. However, its potential roles in aging and neurodegenerative diseases remain poorly understood. In this study, the lifespan of Caenorhabditis elegans was found to be prolonged upon exposure to (1, 10, and 100 μM) stevioside in a dose-dependent manner. Furthermore, we found that stevioside extended the lifespan and healthspan in C. elegans via activation of the ATFS-1-mediated UPRmt pathway. Intriguingly, the amelioration of Alzheimer's disease-related phenotypes by stevioside was also mediated through the ATFS-1 pathway. Additionally, we found that stevioside increased the resistance of oxidative stress and reduced ROS levels and upregulated superoxide dismutase (SOD) activity in C. elegans via the ATFS-1 pathway. These results demonstrated that both the anti-aging and neuroprotective effects of stevioside in C. elegans required a functional ATFS-1-dependent mitochondrial unfolded protein response. Collectively, our work highlighted that stevioside might be a viable candidate for the prevention and treatment of aging and age-related diseases.

DOI: https://doi.org/10.1039/d6fo00251j
Int J Biol Sci. 2026 ;22(9): 4938-4955

Mitochondria and polycystic ovary syndrome: The role of ferroptosis, inflammasomes, and endoplasmic reticulum stress.

Xinyi Zhang, Tong Sun, Xinxin Wang, Yujiu Ma, Liu Cao, Jichun Tan.

  Polycystic ovary syndrome (PCOS) poses a major threat to women of reproductive age and is strongly associated with metabolic and inflammatory abnormalities. Over the past decade, tremendous progress has been made in our understanding of signaling events regulated by mitochondria. Emerging evidence underscores mitochondrial dysfunction as a central pathophysiological hub in PCOS. The intricate crosstalk among mitochondrial dysfunction, ferroptosis, inflammasomes, and endoplasmic reticulum (ER) stress creates a pathological network that underpins ovarian dysfunction, metabolic abnormalities, and chronic inflammation in PCOS, highlighting promising novel targets for diagnosis and therapeutic intervention in this complex disorder.

Keywords:  endoplasmic reticulum stress; ferroptosis; inflammasome; mitochondria; polycystic ovary syndrome

DOI:  https://doi.org/10.7150/ijbs.128537
Maturitas. 2026 May 16. pii: S0378-5122(26)00154-4. [Epub ahead of print]210 108977

A mechanistic digital twin of ovarian aging integrating follicular dynamics, mitochondrial decline, and lifestyle perturbations.

Alexandre Vallée, Anis Feki, Marine Poulain, Jean-Marc Ayoubi.

   BACKGROUND: Ovarian aging determines reproductive lifespan, yet the mechanisms driving inter-individual variability remain incompletely understood. We developed a mechanistic digital twin to investigate how follicular dynamics, mitochondrial energetics, and lifestyle-related oxidative stress jointly shape hormonal trajectories and menopause timing.
METHODS: A system of stochastic differential equations modeled primordial follicle depletion, granulosa cell growth, AMH secretion, mitochondrial decline, and the accumulation of reactive oxygen species (ROS). Smoking, obesity, and circadian disruption modulated oxidative and inflammatory pathways. We simulated 1000 digital twins from ages 18-25 until menopause (AMH <0.1 ng/mL). Monthly outputs included AMH, gonadotropins, estradiol, progesterone, mitochondrial function, ROS, and lifestyle exposures. Parameter uncertainty and key drivers were assessed using posterior sampling and Sobol sensitivity indices.
RESULTS: Simulations reproduced hallmark features of ovarian aging, including exponential AMH decline with realistic values (6.4 ng/mL at 25 years, 1.5 at 35, 0.7 at 40), widening inter-individual divergence after age 40, loss of endocrine cyclicity, and a right-skewed menopause age distribution (median ≈47 years). Mitochondrial function declined progressively while ROS accumulated, forming a tightly coupled aging axis. Lifestyle perturbations produced differentiated effects consistent with epidemiological evidence. Smoking exerted the strongest impact, advancing AMH depletion by approximately 1.5-2 years. Obesity induced chronic low-grade inflammation with modest mitochondrial impairment. Circadian disruption destabilized steroid hormone rhythms and advanced AMH decline by approximately 1 year.
CONCLUSION: This mechanistic digital twin captures realistic endocrine aging patterns and quantifies how modifiable lifestyle factors accelerate ovarian aging through mitochondrial and oxidative pathways, enabling an individualized prediction of reproductive aging.

Keywords:  Anti-Müllerian hormone; Digital twin; Follicle dynamics; Mechanistic modelling; Menopause prediction; Mitochondrial dysfunction; Ovarian aging; Oxidative stress; Stochastic differential equations

DOI:  https://doi.org/10.1016/j.maturitas.2026.108977
J Int Soc Sports Nutr. 2026 Dec 31. 23(1): 2668435

Creatine monohydrate for lean mass, strength, and bone density in postmenopausal women: a systematic review and meta-analysis.

Siavash Naddafha, Jose Antonio, Richard B Kreider, Jeffrey R Stout.

   BACKGROUND: Menopause is accompanied by accelerated losses in muscle mass and strength and declining bone density. Whether creatine monohydrate benefits postmenopausal women are uncertain.
METHODS: We systematically reviewed randomized, placebo-controlled trials examining creatine supplementation, with or without resistance training (RT), in postmenopausal women. MEDLINE, Embase, Scopus, Web of Science, SPORTDiscus, and Cochrane CENTRAL were searched from 2000 to August 2025, supplemented by trial registries and reference-list screening. Eligible studies included postmenopausal women aged ≥40-45 years, intervention durations ≥6 weeks for primary analyses, and outcomes including DXA-derived lean mass, one-repetition maximum (1RM) strength, bone mineral density, physical function, and safety. Dual screening, duplicate extraction, and Cochrane RoB 2 assessment were performed. Random-effects meta-analysis used the Paule-Mandel estimator for τ² with Hartung-Knapp-Sidik-Jonkman adjustment. Heterogeneity (τ², I²), 95% prediction intervals, subgroup analyses by RT status, exploratory dose/duration meta-regression, small-study effects, and GRADE certainty were assessed.
RESULTS: Seven RCTs (n = 608 randomized; duration 12-104 weeks, median 38 weeks) enrolled postmenopausal women (mean age ≈ 62 y). Lean mass (k = 5; n = 338) favored creatine: mean difference (MD) + 0.37 kg (95% CI + 0.05 to + 0.69; I² = 25%; τ² = 0.01; 95% PI -0.10 to + 0.84). Leg-press 1RM (k = 3; n = 111) improved with creatine: MD + 7.5 kg (95% CI + 2.2 to + 12.8; I² = 0%). Benefits were evident when creatine ≥ 5 g·day⁻¹ was combined with RT; trials using ≤ 3 g·day⁻¹ without RT showed no measurable effect. Bone density was unchanged overall. Adverse events were mild and similar to placebo; renal indices were unchanged. Risk of bias was mostly "some concerns;" one large, preregistered, double-blind RCT was at low risk.
CONCLUSIONS: In postmenopausal women, creatine, particularly ≥ 5 g·day⁻¹ with RT, yields small but meaningful gains in lean mass and strength without evidence of harm. Effects on bone density remain unclear.Registration: This review was not prospectively registered. De-identified data and supplementary materials were deposited on OSF after completion of the analysis (DOI: 10.17605/OSF.IO/BVTRZ).

Keywords:  Aging; ergogenic aid; muscle function; osteoporosis; resistance training; sarcopenia

DOI:  https://doi.org/10.1080/15502783.2026.2668435
Ageing Res Rev. 2026 May 15. pii: S1568-1637(26)00174-1. [Epub ahead of print]119 103182

17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.

Roberto Santín-Márquez, Michal Fornalik, Sean R Janovic, Jose V V Isola, Subhasri Biswas, Roshini Sathiaseelan, Jillian E J Cox, Sarah R Ocanas, Michael B Stout.

  Estrogens are pleiotropic hormones that regulate reproductive and non-reproductive physiological processes in both sexes. Among these, 17α-estradiol (17α-E2), a C17 epimer of the canonical estrogen 17β-estradiol (17β-E2), has emerged as a promising modulator of aging and metabolism with sexual dimorphism. Unlike 17β-E2, which exerts broad estrogenic effects in both sexes, 17α-E2 extends lifespan and preferentially improves metabolic homeostasis in male mice while inducing only mild feminizing effects. Many of these benefits are mediated through estrogen receptor alpha (ERα). However, it remains unknown if its biological actions are mediated through genomic or nongenomic pathways and what the molecular basis is for male-biased efficacy. This review outlines evidence from preclinical models and translational studies, demonstrating that 17α-E2 mitigates age-related metabolic declines in males by reducing adiposity, enhancing insulin sensitivity, and preserving hepatic metabolic plasticity. Elucidating the sexually divergent actions of 17α-E2 can advance our understanding of sex-biased endocrine signaling and how these pathways modulate aging in a sex-specific manner.

Keywords:  17α-estradiol; Aging; Estrogen receptor; Healthspan; Lifespan; Metabolism; Sex differences

DOI:  https://doi.org/10.1016/j.arr.2026.103182
Aging Cell. 2026 Jun;25(6): e70517

Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals.

Kamil Pabis, Weilan Wang, Kumar Selvarajoo, Yelena V Budovskaya, Vincenzo Sorrentino, Jan Gruber, Brian K Kennedy.

  In this cross-sectional cohort we analyzed data from 4260 "health enthusiasts" who purchased at least one saliva-based DNA epigenetic test between 2020 and 2025 and completed detailed lifestyle and supplement questionnaires. A proprietary 9-CpG clock with a mean absolute error of 5.4 years served as the primary biomarker of biological age. High prevalence (71%) of supplement use in this cohort increased our power to study the effects of supplements compared to earlier studies that focused on the general population. We tested the association between 84 commonly used supplements and biological age measured as Age Residual. In our cross-sectional analysis, a commercially available, delayed-release calcium-alpha-ketoglutarate (dAKG) + vitamin supplement ("Rejuvant") was associated with an average 1.8-year lower Age Residual. The difference remained significant in models adjusted for age, sex, smoking, health status and additional covariates. In contrast, participants who reported taking regular AKG showed a much smaller and statistically insignificant benefit. Among medications, there was a non-significant benefit of antihistamine use, although the analysis was sample-size limited. In a longitudinal subset, intake of coenzyme Q10 (CoQ10) and dAKG was associated with increased odds of a lower Age Residual, but the results were not significant after multivariate correction. In conclusion, this study underscores the utility of an inexpensive saliva-based epigenetic test for population-level aging research and the benefits of health enthusiast cohorts. It highlights AKG and CoQ10, among others, as promising supplements warranting further investigation. Limitations like healthy user and recruitment bias remain and will require future controlled trials to fully address.

Keywords:  AKG; aging; biological clocks; coenzyme Q10; epigenetic clock; geroprotectors; polypharmacy; real‐world cohort; supplements

DOI:  https://doi.org/10.1111/acel.70517
Reprod Health. 2026 May 18.

Age at menopause and risk of sarcopenia in postmenopausal women: evidence from the China health and retirement longitudinal study.

Yachai Li, Liang Qin, Yan Wang, Shentai Li, Li Ling, Nan Jia.

   BACKGROUND: Menopausal age is closely associated with women's health, but research on its association with sarcopenia risk remains insufficient. Our study aimed to explore how menopausal age affects the risk of sarcopenia in postmenopausal women.
METHODS: Based on the China Health and Retirement Longitudinal Study (CHARLS) database, we included 3,410 postmenopausal women from 2011-2015. Participants were divided into five groups according to menopausal age: premature menopause (< 40 years), early menopause (40-44 years), intermediate menopause (45-49 years), normal menopause (50-55 years), and late menopause (> 55 years). Sarcopenia was identified using the 2019 Asian Working Group for Sarcopenia (AWGS 2019) criteria. Mixed-effects logistic regression models were used to analyze the association between menopausal age and sarcopenia.
RESULTS: The study included 3,410 postmenopausal women with a mean age of 64.39 ± 8.68 years and overall sarcopenia prevalence of 35.40%. Compared to the average age at menopause group (50-55 years; 1,593/3,410; 46.70%), premature menopause (127/3,410; 3.70%), early menopause (385/3,410; 11.30%), intermediate menopause (1,098/3,410; 32.20%), and late menopause (207/3,410; 6.10%) were all associated with increased sarcopenia risk. Compared to normal menopause (50-55 years), early menopause (40-44 years), intermediate menopause (45-49 years), and late menopause (> 55 years) were associated with statistically significant increased sarcopenia risk, while premature menopause (< 40 years) showed a non-significant elevated risk (OR = 1.40, 95% CI: 0.89-2.21, p = 0.1438). This association was stronger among women with late menarche, rural residence, married status, non-retirement, or low education levels.
CONCLUSIONS: Both earlier and later than average menopausal age may be associated with increased sarcopenia risk in Chinese postmenopausal women, although the association for premature menopause did not reach statistical significance in fully adjusted models.

Keywords:  Age at menopause; Middle-aged and elderly women; Sarcopenia; Women's health

DOI:  https://doi.org/10.1186/s12978-026-02358-1
Biochem Res Int. 2026 ;2026 6641383

Mitochondrial Dysfunction in MASLD: Evidence in Dietary Models and Potential Therapeutic Interventions.

Elda Cristina Villaseñor-Tapia, Edgar Rubén Mendieta-Condado, David Alejandro Curiel-Pedraza, Edwin Estefan Reza-Zaldívar, Ana Laura Márquez-Aguirre.

  Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined as the presence of excess triglyceride storage in the liver in the presence of at least one cardiometabolic risk factor. This term highlights the connection between fatty liver and metabolic dysfunction. Dietary factors, such as excessive consumption of saturated fats and sugar, contribute significantly to the accumulation of lipids in organs not specialized for fat storage, such as the liver. Hepatic lipid accumulation initiates dynamic changes in mitochondrial function and promotes the development and progression of MASLD. High-fat, high-fructose diet models have provided crucial insights into how nutritional factors induce mitochondrial dysfunction, which is characterized by impaired fatty acid oxidation, excessive generation of reactive oxygen species, and damage to mitochondrial DNA. Lifestyle modifications, including dietary adjustments such as calorie restriction and weight loss, are essential for the early prevention and long-term treatment of MASLD. However, in recent years, several pharmacological options have emerged for the treatment of MASLD, primarily for the management of its comorbidities. This review explores the mechanisms of mitochondrial dysfunction promoted by the accumulation of hepatic lipids, analyzes the evidence of mitochondrial alterations in the liver of dietary models, and summarizes some of the main therapeutic interventions for MASLD and their effects on mitochondrial function.

Keywords:  lipid metabolism; metabolic dysfunction–associated steatotic liver disease (MASLD); mitochondrial dysfunction

DOI:  https://doi.org/10.1155/bri/6641383
Front Neurol. 2026 ;17 1782114

Effect of mitochondrial dysfunction on scar formation after spinal cord injury.

Yuchen Zhang, Zhengxin Jin, Bin Ning.

  Spinal cord injury (SCI) triggers a cascade of primary and secondary pathological events that culminate in the formation of glial and fibrotic scars, which constitute a major barrier to axonal regeneration and functional recovery. Emerging evidence highlights mitochondrial dysfunction as a central driver of this process. Mitochondria are essential for sustaining ATP production, maintaining redox balance, and regulating calcium homeostasis. Following SCI, direct mechanical disruption, oxidative stress, and calcium overload impair mitochondrial integrity, leading to energy metabolism collapse, excessive reactive oxygen species (ROS) accumulation, and disrupted mitochondrial dynamics. These alterations promote reactive gliosis, fibroblast activation, and maladaptive extracellular matrix deposition. Furthermore, defective mitophagy amplifies neuroinflammation and glial scar consolidation through the PINK1/Parkin and BNIP3/NIX pathways. Recent advances in mitochondrial-targeted therapies-including antioxidants (MitoQ, SS-31), metabolic modulators (AMPK agonists, NAD+ precursors), and strategies enhancing fusion or mitophagy-have demonstrated promising results in reducing scar formation and promoting neural repair. In addition, cutting-edge approaches such as mitochondrial transplantation, stem cell-derived mitochondrial transfer, and CRISPR-based mitochondrial gene editing provide new opportunities for restoring mitochondrial homeostasis. This review summarizes the multifaceted roles of mitochondrial dysfunction in SCI-induced scar formation and discusses novel therapeutic strategies targeting mitochondrial metabolism and dynamics to enhance neural regeneration.

Keywords:  fibrotic scar; glial scar; mitochondrial dynamics; mitochondrial dysfunction; oxidative stress; spinal cord injury

DOI:  https://doi.org/10.3389/fneur.2026.1782114
Handb Exp Pharmacol. 2026 May 23.

Mitochondrial Dysfunction Contributes to Endothelial Damage in Metabolic Diseases: Role of Mitochondrial DNA in Inflammation.

Mónica M Velásquez-Esparza, Rodrigo López-Velázquez, Andrés Cázares-Preciado, Hipólito O Miranda-Roblero, Perla Pérez-Treviño, Carlos Enrique Guerrero-Beltrán, Noemí García.

  Endothelial cells (ECs) have a low mitochondrial density, around ~2-6% of cell volume, compared to cardiac cells (~32%). Consequently, ATP is generated mainly by the glycolytic pathway. The role of the mitochondrial network in ECs gains relevance as a signaling hub that modulates a wide range of endothelial functions, e.g., regulation of cell migration, proliferation, and angiogenesis, through the action of second messengers such as Ca2+ and reactive oxygen species (ROS). However, under stress conditions, such as lipotoxicity, the homeostasis of Ca2+ and ROS is disrupted due to an imbalance in the antioxidant system, leading to an oxidative stress state. In addition, the K+-channels are inhibited, causing membrane depolarization and contributing to the disruption of ionic homeostasis. This increases free Ca2+ in the cytosol and mitochondria, resulting in the opening of mitochondrial permeability transition (MPTP) and mitochondrial dysfunction. MPTP allows the escape of mitochondrial components, such as cytochrome c, ions, and even mitochondrial DNA (mtDNA) to the cytosol. Cytosolic mtDNA migrates to the endosome to interact with TLR-9 to activate the inflammation pathway. Then mtDNA is secreted by exosomes to propagate the inflammation signal to other cells.Endothelial dysfunction in obesity, metabolic syndrome, type 2 diabetes, diabesity, and cardiometabolic disease is promoted by lipotoxicity, increased oxidative stress, and inflammation. The relationship between these mechanisms likely involves the interaction of mtDNA and other mitochondrial components (e.g., HSP60) with pro-inflammatory receptors, e.g., TLR-9.

Keywords:  DAMPs; HSP60; Interleukins; Lipotoxicity; Mitochondrial DNA; TLRs

DOI:  https://doi.org/10.1007/164_2026_805
Int J Endocrinol Metab. 2026 Jan 31. 24(1): e167142

Legacy of Tehran Lipid and Glucose Study; Evidence on Reproductive Lifespan and Cardiometabolic Health.

Maryam Farahmand, Maryam Mousavi, Marzieh Saei Ghare Naz, Mahbanoo Farhadi-Azar, Mahsa Noroozzadeh, Fereidoun Azizi, Fahimeh Ramezani Tehrani.

   Context: Understanding the different reproductive factors and their link to non-communicable diseases (NCDs) is crucial in a community-based cohort study. The present study provides a comprehensive synthesis of published findings derived from the Tehran lipid and glucose study (TLGS) pertaining to women, offering insights into the epidemiological patterns of reproductive lifespan and its impact on cardiometabolic parameters.
Evidence Acquisition: We conducted a thorough review of all studies on reproductive lifespan conducted within the TLGS framework.
Results: Overall, the mean (SD) age at menarche among participants was 13.35 (1.5) years, whereas the mean (SD) age at menopause was 50.16 (5.7) years. Early menarche was identified as a significant factor associated with later metabolic impairments, including higher odds of prediabetes (OR: 2.7; 95% CI: 1.1 - 6.6), type 2 diabetes mellitus (DM) (OR: 3.6; 95% CI: 1.2 - 10.7), and metabolic syndrome (MetS) (OR: 2.3; 95% CI: 1.1 - 5.4) in fully adjusted models. Comparisons between surgical and natural menopause revealed that the incidence of MetS was nearly tenfold higher among women who experienced surgical menopause, accompanied by elevated mean fasting plasma glucose (FPG) and 2‑hour post‑load glucose concentrations. Furthermore, each additional year in age at natural menopause was associated with a 10% increase in the incidence of chronic kidney disease (CKD), whereas prolonged exposure to endogenous estrogen appeared to confer protective effects, reducing the incidence of hypertension, cardiovascular disease (CVD), CKD, and osteoporotic fractures. In addition, lactation was found to markedly lower the risk of MetS among women with a prior history of gestational diabetes, emphasizing its potential long‑term cardiometabolic benefits.
Conclusions: The reproductive milestones significantly shape women's long‑term cardiometabolic health, supporting the integration of reproductive history into preventive care models and longitudinal risk assessment frameworks.

Keywords:  Endogenous Estrogen Exposure; Hormonal Use; Lactation; Menarche; Menopause; Tehran Lipid and Glucose Study (TLGS)

DOI:  https://doi.org/10.5812/ijem-167142
Free Radic Biol Med. 2026 May 21. pii: S0891-5849(26)00787-2. [Epub ahead of print]

Mitoredox Shifts in Mitochondrial Dysfunction.

Walter H Moos, Douglas V Faller, Ioannis P Glavas, Iphigenia Kanara, Krishna Kodukula, Julie Pernokas, Mark Pernokas, Carl A Pinkert, Whitney R Powers, Konstantina Sampani, Kosta Steliou, Demetrios G Vavvas.

  Mitochondrial dysfunction underlies a broad spectrum of primary and secondary disorders, yet current frameworks do not fully capture how diverse genetic, metabolic, and environmental stressors converge on shared pathological outcomes. Here, we propose that mitoredox shifts - bidirectional disruptions in mitochondrial redox homeostasis that alter mitochondrial quality control and genome-stability pathways - serve as a unifying axis linking oxidative stress, mitochondrial quality control failure, heteroplasmy dynamics, and regulated cell death. Both hyperactive and hypoactive mitochondrial states destabilize redox balance, altering PINK1/Parkin-dependent and receptor-mediated mitophagy, disrupting proteostasis, and reshaping mitochondrial network dynamics. These redox-driven perturbations influence the propagation of pathogenic mtDNA variants, modulate tissue-specific threshold effects, and bias cells toward apoptosis, ferroptosis, cuproptosis, and other regulated cell death pathways. We synthesize emerging evidence across mitochondrial genetics, bioenergetics, and redox signaling to outline how mitoredox shifts accelerate disease progression in both primary mitochondrial syndromes and secondary mitochondrial dysfunction. We further evaluate the expanding landscape of diagnostic biomarkers, including FGF21, GDF15, imaging-based oculomics, and high-throughput proteomic and genomic assays. In parallel, we highlight therapeutic strategies aimed at restoring redox balance, enhancing mitophagy, or shifting mitochondrial network composition by diluting dysfunctional organelles through mitochondrial transplantation. By emphasizing mitoredox imbalance as a recurrent feature of disease, this work synthesizes emerging diagnostic and therapeutic approaches across rare and common mitochondrial disorders.

Keywords:  Biomarkers; cuproptosis; ferroptosis; heteroplasmy; mitochondria; mitophagy; mitoredox medicine; oxidative stress

DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.05.307
Aging Cell. 2026 May;25(5): e70535

Fisetin Supplementation Attenuates Premature Vascular Aging Induced by Doxorubicin via Suppression of Cellular Senescence and Mitochondrial Oxidative Stress.

Mary A Darrah, Sophia A Mahoney, Ravinandan Venkatasubramanian, Nicholas S VanDongen, Katelyn R Ludwig, Douglas R Seals, Matthew J Rossman, Zachary S Clayton.

  The genotoxic agent doxorubicin induces premature vascular aging, defined by vascular endothelial dysfunction and aortic stiffening. Excess vascular cell senescence and the accompanying senescence-associated secretory phenotype (SASP) are key mechanisms underlying doxorubicin-induced vascular dysfunction, in part, by promoting excess mitochondrial oxidative stress, which reduces the bioavailability of the vasodilatory molecule nitric oxide (NO). In the present study, we assessed if the natural senolytic fisetin mitigates doxorubicin-induced cellular senescence and the SASP to improve vascular function following doxorubicin administration and explored the underlying mechanisms. Young adult (6 months) mice were treated with doxorubicin, followed by oral, intermittent fisetin supplementation (100 mg/kg/day; 1 week on treatment-2 weeks off treatment-1 week on treatment). Vascular endothelial function, aortic stiffness, cellular senescence markers, SASP expression, NO bioavailability, and mitochondrial oxidative stress were assessed. Parallel experiments in human aortic endothelial cells were conducted to provide further mechanistic insight. Fisetin mitigated excess vascular cell senescence and the SASP in young mice administered doxorubicin and reversed doxorubicin-induced endothelial dysfunction (p < 0.001) and aortic stiffening (p < 0.001), in part through suppression of excess cellular senescence, higher NO bioavailability, and lower mitochondrial oxidative stress. Modulation of the circulating SASP (plasma) also contributed to the observed vascular improvements with fisetin. In vitro, fisetin reduced cellular senescence in doxorubicin-exposed endothelial cells, supporting isolated artery and in vivo observations. These findings identify oral intermittent fisetin supplementation as a promising therapeutic strategy for targeting excess cellular senescence to improve vascular function in settings of premature vascular aging.

Keywords:  arterial function; cellular senescence; doxorubicin; premature aging; senolytics

DOI:  https://doi.org/10.1111/acel.70535
Kidney Int. 2026 May 21. pii: S0085-2538(26)00394-7. [Epub ahead of print]

Mitochondrial respiratory capacity in kidney podocytes is high, age-dependent, and sexually dimorphic.

Matthew D Campbell, Monica Sanchez-Contreras, Britta D Sibley, Phoebe Keiser, Carla Ruiz-Sanchez, Carolyn N Mann, Anna A Bakhtina, James E Bruce, David J Marcinek, Behzad Najafian, Mariya T Sweetwyne.

   INTRODUCTION: Whether and how podocytes depend on mitochondria across their long post-mitotic lifespan is unclear. With limited cell numbers and broad kidney distribution, isolation of podocyte mitochondria typically requires first isolating podocytes themselves. Disassociation of podocytes from their basement membrane, however, recapitulates an injured state and stresses mitochondria. Here, we devise a new strategy to examine mitochondria in podocytes.
METHODS: To address this, we crossed floxed hemagglutinin (HA)-mitochondria tagged (MITO-Tag) mice with those expressing Cre in either podocytes (NPHS2) or mixed tubules (CDH16), thus allowing for rapid, kidney cell-specific, isolation of mitochondria via immunoprecipitation.
RESULTS: Mitochondrial respiration in fresh isolates from young (4-7 months) and aged (22-26 months) mice of both sexes demonstrated several previously unreported significant differences between podocyte and tubule mitochondria. First, although podocytes contain fewer mitochondria than tubule cells, mitochondria isolated from podocytes averaged twice the respiratory capacity of tubule mitochondria when normalized to mitochondrial content by citrate synthase levels. Second, age-related decline in respiration was detected only in podocyte mitochondria and only in aged male mice. Third, disassociating podocytes for cell culture initiates functional decline in mitochondria as those from cultured primary podocytes have half the respiratory capacity, but twice the hydrogen peroxide production, of podocyte mitochondria isolated directly from fresh kidneys. Finally, conformation of electron transport chain proteins differed between podocyte and tubule mitochondria, suggesting that cell-specific mitochondrial protein conformations dictate cell-specific mitochondrial function.
CONCLUSIONS: Previous studies suggesting a limited role for mitochondrial regulation of podocytes relied on cell culture. This resulted in artifactual suppression of mitochondrial function and masks the roles of mitochondria in maintenance of podocyte health. Our approach shows that per organelle, podocytes maintain sexually dimorphic mitochondria with greater oxidative phosphorylation capacity than the mitochondria-dependent tubules.

Keywords:  animal model; distal tubule; mitochondria; podocyte

DOI:  https://doi.org/10.1016/j.kint.2026.04.016
Acta Diabetol. 2026 May 22.

Reversing diastolic dysfunction in diabetes: a mitochondrial quality control-centric pharmacological approach.

Wenkai Fu, Junqi Wang, Zhijiang Guo, Sang-Bing Ong, Yong Gao, Hang Zhu, Junyan Wang, Zhiyong Du, Miao Meng, Xing Chang.

  Diabetic cardiomyopathy (DCM) is a major contributor to the cardiovascular complications associated with diabetes. This condition is characterized by structural and functional abnormalities of the myocardium that occur independently of factors such as hypertension or other established cardiac diseases. In this review, we focus on the mitochondrial quality control (MQC) system, a critical determinant in the pathogenesis of DCM. In the diabetic milieu, chronic hyperglycemia and lipid overload disrupt mitochondrial homeostasis, leading to oxidative stress, impaired energy metabolism, and dysregulated mitochondrial dynamics. These disturbances serve as precursors to severe pathological outcomes, including cardiomyocyte death, myocardial fibrosis, and the progression of heart failure. This paper systematically examines the four pillars of MQC regulation-mitochondrial dynamics, selective autophagy (mitophagy), mitochondrial biogenesis, and the mitochondrial unfolded protein response (UPRmt)-and discusses how dysregulation of these regulatory networks contributes to the development of DCM. We further explore the molecular mechanisms involving key regulators such as Drp1 and Parkin, emphasizing their potential as therapeutic targets. Although current research has identified promising strategies, including hypoglycemic agents, melatonin, and various natural compounds that modulate MQC in preclinical models, translating these findings into clinical practice remains challenging due to species differences and the inherent complexity of MQC regulation. Future research should prioritize multi-target combination therapies and personalized treatment strategies aimed at preserving mitochondrial homeostasis and delaying the progression of DCM.

Keywords:  Diabetic cardiomyopathy; Mitochondrial homeostasis; Mitochondrial quality control; Oxidative stress

DOI:  https://doi.org/10.1007/s00592-026-02706-4
Am J Transl Res. 2026 ;18(4): 3479-3491

GDF15 predisposes aortic dissection through regulation of vascular smooth muscle cell proliferation and phenotypic change via the ERK/Akt pathway.

Qian Tan, Zhijie Yang, Jianjun Zhang.

   OBJECTIVE: Aortic dissection (AD) represents a life-threatening vascular disorder characterized by abnormal vascular smooth muscle cell (VSMC) behavior and extracellular matrix remodeling. Growth differentiation factor 15 (GDF15) is a stress-related cytokine associated with the pathogenesis of cardiovascular diseases, but its exact role in AD remains to be elucidated.
METHODS: Human aortic smooth muscle cells (HASMCs) were incubated with angiotensin II (Ang II) to simulate an in vitro pathological tension environment. Gain- and loss-of-function experiments were carried out to investigate the functional role of GDF15 in regulating cell growth, migration, phenotypic transformation, and inflammatory reaction. The involvement of the ERK/protein kinase B (Akt) pathway was studied using a ERK inhibitor. Clinical significance was analyzed by detecting the plasma levels of GDF15 and matrix metalloproteinases (MMPs) in AD patients and healthy controls.
RESULTS: Ang II upregulated GDF15 expression in HASMCs in a dose- and time-dependent manner. GDF15 overexpression promoted HASMC proliferation, migration, and phenotypic switching from a contractile to a synthetic state, accompanied by increased expression of MMP-2 and MMP-9 and pro-inflammatory cytokines (TNF-α, IL-6, and MCP-1). GDF15 knockdown produced opposite effects. Mechanistically, GDF15 activated both ERK and Akt pathways; however, pharmacological inhibition experiments suggested that the pro-remodeling effects of GDF15 were primarily mediated through ERK signaling. Clinically, plasma concentrations of GDF15, MMP-2, and MMP-9 were significantly higher in AD patients compared with healthy controls.
CONCLUSIONS: GDF15 promotes aberrant remodeling of HASMCs by enhancing proliferation, migration, phenotypic transformation, and inflammatory responses via ERK-dependent signaling. Elevated plasma GDF15 levels in AD patients suggest that GDF15 can serve as a potential diagnostic biomarker and therapeutic target for AD.

Keywords:  Aortic dissection; ERK/Akt signaling; GDF15; angiotensin II; phenotypic switching; vascular smooth muscle cells

DOI:  https://doi.org/10.62347/KSVK9192
Nutr Rev. 2026 May 19. pii: nuag025. [Epub ahead of print]

Effect of Green Tea Extract Supplementation on Substrate Utilization: A GRADE-Assessed Systematic Review and Dose-Response Meta Analysis of Randomized Controlled Trials.

Amir Hossein Khalilkhaneh, Mohammad Vesal Bidsheki, Salih M S Zebari, Sepide Talebi, Arefeh Mohajerani, Kurosh Djafarian.

   CONTEXT: Several studies have assessed the effects of green tea extract (GTE) supplementation on substrate oxidation. However, no consensus has been reached due to the heterogeneity of the results, and so far no meta-analysis has been conducted on this topic.
OBJECTIVE: This systematic review and meta-analysis aimed to critically evaluate the effects of GTE supplementation on substrate oxidation, particularly on fat and carbohydrate oxidation during and after exercise.
DATA SOURCES: We conducted a comprehensive search of databases, including PubMed, Web of Science, and Scopus, to identify studies relevant to our research up until December 2024.
DATA EXTRACTION: Eligible randomized controlled trials (RCTs) that reported relevant and adequate data about substrate oxidation were included in this meta-analysis. Also, we rated the evidence certainty using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) method.
DATA ANALYSIS: Nine clinical trials evaluated the effect of GTE supplementation on substrate oxidation during and after exercise. In summary, intervention with GTE significantly increased fat oxidation both during (weighted mean difference [WMD]: 0.2 g/min; 95% CI; 0.04, 0.36; P = .016) and after exercise (WMD: 0.04 g/min; 95% CI; 0.01, 0.08; P = .023). Also, GTE significantly decreased carbohydrate oxidation after exercise (WMD: -0.16 g/min; 95% CI; -0.32, -0.01; P = .04) but did not significantly affect carbohydrate oxidation during exercise (WMD: -0.08 g/min; 95% CI; -0.29, 0.13; P = .468). Furthermore, the results of the dose-response analysis showed that an increase in the dose of GTE could augment fat oxidation after exercise (WMD: 0.03 g/min; 95% CI: 0.01, 0.06, P = .007). The quality of evidence was rated as low to high according to the GRADE criteria.
CONCLUSION: Green tea extract supplementation significantly enhances fat oxidation during and after exercise, with limited effects on carbohydrate oxidation.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD42024598165.

Keywords:  exercise; green tea extract; meta-analysis; substrate utilization

DOI:  https://doi.org/10.1093/nutrit/nuag025
Cell Mol Neurobiol. 2026 May 20.

Soluble Fiber Intake Restores the Estrous Cycle and Sex Hormone Alterations in APP/PS1 Female Mice.

Ivonne Sagrario Romero-Flores, Daniel Cuervo-Zanatta, Roberto Chavira, Vicente Sánchez-Valle, Jaime García-Mena, Claudia Perez-Cruz.

Alzheimer's disease (AD) is the most common form of dementia, with a higher prevalence in women than in men. It has been suggested that the decline in estrogen production after menopause may increase the risk of developing dementia. We have previously shown that transgenic female APP/PS1 mice, overexpressing APP and PS1 proteins, develop spontaneous gut dysbiosis with a consequent dysfunctional estrobolome leading to higher estradiol excretion rate compared to age-matched wildtype (WT) females. It has been demonstrated that soluble fiber intake restores gut microbiota dysbiosis, reduces anxiety and improves cognitive function in APP/PS1 male mice. Therefore, the aim of this study was to evaluate if the intake of soluble fiber can modify the gut microbiota composition, alleviating the estrobolome dysfunction, and restoring sex-hormone alterations in female APP/PS1 mice. We confirm that six-month-old APP/PS1 female mice develop a spontaneous gut dysbiosis, an estrobolome dysfunction, and lower oestrous cycle frequencies than their WT littermates. Soluble fiber intake modulates the gut microbiota composition and increases beta-glucuronidase activity in faecal samples associated with a restoration of estradiol and DHEA plasma levels. Additionally, consuming soluble fiber affects various bacterial metabolic pathways and enhances the production of butyrate and acetate. Improved memory and cognitive performance were also observed in female APP/PS1 mice that were fed fructans. Therefore, soluble fiber intake may represent a preventive strategy to mitigate the alterations associated with the onset of reproductive senescence and dementia in females.

DOI: https://doi.org/10.1007/s10571-026-01745-3
Sci Rep. 2026 May 21.

Fucoxanthin improves stomatitis by regulating mitochondrial function and cGAS-STING signaling.

Caipeng Lin, Lili Deng, Xi Xie, Hai-Bin Luo, Deyu Liu.

  Fucoxanthin (FX), a natural carotenoid derived from marine brown algae, possesses extremely high anti-inflammatory activity. However, the precise mechanisms underlying its protective effects against stomatitis remain to be elucidated. This study aimed to explore the protective effects and mechanisms of FX in the treatment of stomatitis. Histopathological examination was conducted on oral mucosal tissues from rats with 5-fluorouracil (5-FU)-induced oral mucositis. Western blotting and immunofluorescence staining were used to explore the epithelial-mesenchymal transition (EMT), tight junction proteins, mitochondrial function, mitochondrial autophagy and the expression of key molecules involved in the cGAS-STING signaling in HOKs. Moreover, molecular docking analysis was applied to predict the binding interactions between FX and cGAS/STING proteins. The results showed that FX markedly alleviated the symptoms of whitening and swelling of the oral mucosa and thinning of the epithelium in 5-FU-induced rats. In LPS-induced HOKs, FX restored the abnormal localization of Occludin and ZO-1 proteins, ameliorated mitochondrial dysfunction, and inhibited EMT. Furthermore, the protein levels of cGAS, STING, and TBK1 were downregulated by FX treatment. Molecular docking revealed direct binding between FX and both cGAS and STING. Collectively, these findings indicate that FX may alleviate LPS-induced stomatitis by ameliorating mitochondrial dysfunction to reduce mitochondrial DNA (mtDNA) release, thereby inhibiting the cGAS-STING signaling pathway. These results suggest that FX holds promise as a therapeutic candidate for stomatitis.

Keywords:  Fucoxanthin; Mitochondrial function; Stomatitis; cGAS-STING signaling

DOI:  https://doi.org/10.1038/s41598-026-53680-4
Int J Psychophysiol. 2026 May 21. pii: S0167-8760(26)00101-7. [Epub ahead of print] 113418

Breathing slower is not always better: Slow-paced breathing enhances heart rate variability but produces age-differential effects on emotional reactivity and memory.

Pierrick Laulan, Ulrike Rimmele.

  Slow-paced breathing (SPB) is commonly used to promote autonomic regulation and emotion regulation, but its effects on emotional memory, and whether these extend to older adults, have received little attention. We examined whether SPB during memory encoding would modulate heart rate variability (HRV), emotional reactivity, and recognition memory differently from normal-paced breathing (NPB) in younger (n = 82) and older (n = 84) adults. Participants breathed at either 6 breaths/min (SPB) or 12 breaths/min (NPB) while encoding negative and neutral images, then completed a recognition test with Remember/Know judgments. Both breathing conditions produced robust increases in task-related HRV, with no reliable difference between SPB and NPB; effects were comparable across age groups. SPB reduced overall emotional intensity and tended to dampen perceived negativity, though not in a valence-specific manner. At the memory level, older adults showed lower discrimination than younger adults, particularly for negative images, consistent with accounts of an age-related positivity effect characterized by a reduced advantage of negative over neutral material. SPB reduced false alarms and improved discrimination in younger adults, whereas older adults showed comparable performance across conditions. SPB reduced spurious recollection (Remember responses to lures) while preserving recollection of targets, and this effect did not differ by age group. Exploratory mediation analyses showed that task-related RMSSD did not significantly mediate the effects of breathing condition on any outcome, leaving unresolved whether the observed psychological effects depended on central, peripheral, or distributed mechanisms. Thus, slower breathing is not uniformly better: both paced-breathing conditions enhanced task-related HRV, whereas SPB reduced emotional intensity regardless of age and improved memory only in younger adults.

Keywords:  Aging; Emotional memory; Heart rate variability; Recognition memory; Slow-paced breathing

DOI:  https://doi.org/10.1016/j.ijpsycho.2026.113418
Neurochem Res. 2026 May 22. pii: 171. [Epub ahead of print]51(3):

Alkaloids from Dendrobium Nobile Lindl Improves Mitochondrial Function by Enhancing the Activity of v-ATPase in APP/PS1 Mice.

Qiye Li, Yan Yang, Bin Guo, Xuejia Liu, Guohui Luo, Yajuan Wu, Jing Nie.

  Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuronal loss and cognitive deficiency. Mitochondrial dysfunction and lysosomal abnormalities are critical during AD pathogenesis. The vesicular ATPase (v-ATPase) is a core regulator of lysosomal function, and its dysfunction impairs iron-sulfur protein synthesis and mitochondrial function. In this study, 4-month-old amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice were treated with alkaloids from Dendrobium nobile Lindl (DNLA) at 20 and 40 mg/kg/day via oral gavage for 5 months (n = 10 per group). The Y-maze test showed that DNLA alleviated cognitive dysfunction in APP/PS1 mice. HE, Nissl, and β-galactosidase staining indicated that DNLA mitigated brain damage. DNLA also increased the protein levels of v-ATPase subunits ATP6V1A and ATP6V0a1 in the cortex, promoted mitochondrial iron uptake and utilization, enhanced mitochondrial function, and reduced neuronal damage. Dendrobine (DDB) accounted for 84.6% in DNLA used for animal experiments, and purified DDB (99.7%) was applied for in vitro assays. In PC12 cells, DDB restored ATP6V1A expression, enhanced v-ATPase activity, delayed cellular senescence, improved iron utilization, and elevated mitochondrial membrane potential and ATP levels in ATP6V1A-knockdown cells. These findings suggest that DNLA may attenuate learning and memory impairment in APP/PS1 mice. The mechanism may be related to enhanced v-ATPase activity, promoted mitochondrial iron uptake and utilization, and improved mitochondrial function.

Keywords:  APP/PS1 mice; Alkaloids from Dendrobium nobile Lindl; Alzheimer's disease; Mitochondria; V-ATPase

DOI:  https://doi.org/10.1007/s11064-026-04778-8