bims-mistre 2025-11-23 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–11–23
seventeen papers selected by
Ellen Siobhan Mitchell, MitoQ

Mitochondria serve as indispensable components of neuron-glia crosstalk in the trajectory of Alzheimer's disease.
Metabolic Flexibility of Microglia: Energy Substrate Utilization and Impact on Neuronal Metabolism.
Ovarian Aging: Mechanisms, Age-Related Disorders, and Therapeutic Interventions.
A scalable step count-based predictor of biological age: development and validation of MoveIt! Age in community-dwelling adults and geriatric rehabilitation inpatients.
Beyond Estrogen: Unraveling the Complexities of Hormonal Signaling Pathways in Alzheimer's Disease and Their Implications for Precision Therapy.
The effects of Rosa damascene aromatherapy on mood and sleep: a systematic review and meta-analysis.
Mitochondrial Respiratory Supercomplex Assembly Factor COX7RP Contributes to Lifespan Extension in Mice.
Effects of supplementation with two probiotic strains (Lactobacillus helveticus and Bifidobacterium longum) on hormonal status, oxidative stress, and clinical symptoms in women with polycystic ovary syndrome: a randomized clinical trial.
Docosahexaenoic acid enhances porcine oocyte maturation via AMP-mediated improvement of mitochondrial function and energy metabolism.
Causal effects of dietary antioxidants on epigenetic age: A two-sample Mendelian randomization study.
Taurine promotes porcine oocyte maturation and embryonic development by reducing oxidative stress and enhancing energy metabolism.
Pharmacological Stimulation of GPER Reverses Mitochondrial Dysfunction in the Hearts of Ovariectomized Type 2 Diabetic Rats.
Effects of Ashwagandha on Reproductive Health: A Systematic Review of Sex-Specific Hormonal and Fertility Outcomes.
Epigenetic Aging and Treatment Response to Semaglutide in the SLIM LIVER Study.
The Canadian Network for Mood and Anxiety Treatments Task Force Recommendations for the Use of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplants in Adults With Major Depressive Disorder: Recommandations du Groupe de travail du Réseau canadien pour le traitement des troubles de l'humeur et de l'anxiété (Canadian Network for Mood and Anxiety Treatments, CANMAT) concernant l'utilisation des probiotiques, des prébiotiques, des symbiotiques et de la transplantation de microbiote fécal chez les adultes atteints de trouble dépressif majeur.
Mitochondrial NAD+ gradient sustained by membrane potential and transport.
Potential dietary geroprotectors and their impact on key mechanisms of aging.

Brain Res. 2025 Nov 18. pii: S0006-8993(25)00603-1. [Epub ahead of print] 150040

Mitochondria serve as indispensable components of neuron-glia crosstalk in the trajectory of Alzheimer's disease.

Maryam Sardari, Oveis Hosseinzadeh Sahafi, Ameneh Rezayof.

  Alzheimer's disease (AD) is a multiplex and progressive neurodegenerative disorder commonly recognized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs), and dysfunction in the cholinergic and glutamatergic systems. At the early stages of AD, mitochondrion operates as a neuroprotective organelle in both neuronal and glial cells by compensating energy fluctuations. As the disease progresses, mitochondrial function in both neurons and glial cells deteriorates, culminating in impaired cellular metabolism and glial hyperactivation. This time-dependent hyperactivation of microglia and astrocytes sequentially promotes the release of pro-inflammatory cytokines, elevates reactive oxygen species, disrupts calcium homeostasis, and increases oxidative stress. Altogether, these processes drive neuroinflammation, which both influences and is influenced by mitochondrial activity. Additionally, mitochondrial dysfunction across the disease trajectory hampers communication between neurons and glial cells, promoting excitotoxicity in neurons. This review emphasizes the vital role of mitochondrial dynamics in AD pathophysiology across different stages and explores how cell-specific targeting of mitochondrial activity could mitigate neuroinflammation, restore neuronal function, and offer potential treatment benefits. Enhancing mitochondrial function in healthy neurons and glial cells, particularly in microglia as a compensatory mechanism, especially at the early stage of the disease or restoring mitochondrial function of surviving neurons at the later stages, may promote neuroprotection and improve neuron-glia interactions, thus offering a potential strategy for AD treatment.

Keywords:  Alzheimer’s disease; Glial cells; Mitochondrial dynamics; Neuroinflammation

DOI:  https://doi.org/10.1016/j.brainres.2025.150040
J Neurochem. 2025 Nov;169(11): e70304

Metabolic Flexibility of Microglia: Energy Substrate Utilization and Impact on Neuronal Metabolism.

Emil W Westi, Rebecca Birch Carlsen, Jens Velde Andersen, Zeliha Kilic, Dana Alnajar, Nadia K Holmgaard, Belén García Sintes, Agustin Cota-Coronado, Sonia Sanz Muñoz, Céline Galvagnion, Blanca I Aldana.

  Microglia, the main resident immune cells of the brain, play critical roles in maintaining neuronal function and homeostasis. Microglia's metabolic flexibility enables rapid adaptation to environmental changes, yet the full extent of their metabolic capabilities and influence on neuronal metabolism remains unclear. While microglia predominantly rely on glucose oxidative metabolism under homeostatic conditions, they shift towards glycolysis upon proinflammatory activation. In this study, we investigated microglial metabolism and its impact on neuronal metabolic homeostasis using isotope tracing with stable carbon 13C-enriched substrates and gas chromatography-mass spectrometry (GC-MS) analysis. Primary microglia were incubated with 13C-labeled glucose, glutamine, or GABA in the presence or absence of lipopolysaccharide (LPS) to assess metabolic adaptations upon an inflammatory challenge. Additionally, neurons co-cultured with quiescent or activated microglia (either with LPS or amyloid-β) were incubated with 13C-enriched glucose to examine microglia-neuron metabolic interactions. Our findings confirm that microglia readily metabolize glucose and glutamine, with LPS stimulation slightly changing the glycolytic activity, as indicated by subtle changes in extracellular lactate. Importantly, we demonstrate for the first time that microglia take up and metabolize the inhibitory neurotransmitter GABA, suggesting a novel metabolic function. Furthermore, microglial presence directly influences neuronal metabolism and neurotransmitter homeostasis, highlighting a previously unrecognized aspect of neuron-microglia metabolic crosstalk. Collectively, these findings provide new insights into microglial metabolism and its role in neuronal function, with implications for neuroinflammatory and neurodegenerative diseases in which microglial metabolism is dysregulated.

Keywords:  GABA metabolism; amyloid‐beta; glutamine; metabolic flexibility; neuroimmune interactions; neurons

DOI:  https://doi.org/10.1111/jnc.70304
MedComm (2020). 2025 Dec;6(12): e70481

Ovarian Aging: Mechanisms, Age-Related Disorders, and Therapeutic Interventions.

Xingyu Liu, Yuanqu Zhao, Yanzhi Feng, Shixuan Wang, Jinjin Zhang.

  Ovarian aging is a fundamental process in female reproductive biology with broad implications for overall health and aging. As global populations age, understanding its mechanisms and systemic effects has gained urgent clinical relevance. The ovary, beyond its reproductive role, is increasingly recognized as a regulator of systemic aging due to the widespread presence of estrogen receptors. Declining ovarian function accelerates not only reproductive senescence but also contributes to age-related disorders including osteoporosis, neurodegenerative diseases, and cardiovascular conditions. However, research on ovarian aging remains fragmented, lacking integrative analysis. This review synthesizes recent advances in the cellular and molecular mechanisms underpinning ovarian aging, such as genomic instability, metabolic and oxidative stress, and microenvironmental alterations. It further discusses how ovarian decline influences systemic aging pathways and disease susceptibility and evaluates emerging therapeutic strategies such as antioxidant interventions, stem cell therapy, and ovarian tissue transplantation. By providing a comprehensive overview of ovarian aging from mechanisms to interventions, this review aims to bridge existing knowledge gaps and inspire future research toward improving women's healthspan and quality of life.

Keywords:  age‐related diseases; mechanism; ovarian aging; therapeutic interventions

DOI:  https://doi.org/10.1002/mco2.70481
Geroscience. 2025 Nov 15.

A scalable step count-based predictor of biological age: development and validation of MoveIt! Age in community-dwelling adults and geriatric rehabilitation inpatients.

Jessica K Lu, Weilan Wang, Lihuan Guan, Jeroen van der Velde, Joris Hoeks, Patrick Schrauwen, Gajja S Salomons, Riekelt H Houtkooper, Andrea B Maier, Georges E Janssens.

  Measuring biological age typically requires invasive and costly procedures. To address this, the MoveIt! Age Score was developed: a simple, scalable, and interpretable aging clock that predicts biological age using only wearable-derived steps data. MoveIt! Age was trained on steps data from the United States National Health and Nutrition Examination Survey (NHANES), using chronological age, maximum step count, and step count variability to predict PhenoAge, a blood biochemistry biological age score. MoveIt! Age performance was evaluated in two independent cohorts: Mitochondria and Muscle Health in Elderly (MitoHealth; N = 55; healthy young adults or older adults from the Netherlands) and Restoring Health of Acutely Unwell Adults (RESORT; N = 145; geriatric rehabilitation inpatients from Australia). In RESORT, MoveIt! Age was assessed and compared to SenoClock-BloodAge and PhenoAge (hematological aging clocks). Delta age was the predicted biological age minus chronological age. In the NHANES testing dataset, MoveIt! Age demonstrated high predictive accuracy of chronological age (r = 0.97, RMSE = 5.4 years) and was more significantly associated with mortality than PhenoAge. In MitoHealth, delta MoveIt! Age showed differences between young adults and older adults who were normal, healthy, or health-impaired, with MoveIt! Age more significantly associated with muscle NAD+ levels (r = -0.37, p = 0.023) than chronological age (p = 0.416). Delta MoveIt! Age associated more strongly than other clocks with physical function outcomes, including frailty, handgrip strength, and functional performance. These findings support MoveIt! Age as a practical tool to gain insights into biological age in both clinical and community settings.

Keywords:  Aging; Biological age; Longevity; Physical fitness; Wearable electronic devices

DOI:  https://doi.org/10.1007/s11357-025-01999-7
Mol Neurobiol. 2025 Nov 19. 63(1): 77

Beyond Estrogen: Unraveling the Complexities of Hormonal Signaling Pathways in Alzheimer's Disease and Their Implications for Precision Therapy.

Sumaya Nadhim Mohammed, Thanyaporn Direksunthorn, Ahmed Hussein Zwamel, Subasini Uthirapathy, Suhas Ballal, Rishiv Kalia, Renu Arya, K Satyam Naidu, Irfan Ahmad, Jawad Kadhim Ahmed.

  Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs), leading to cognitive decline. Women, particularly postmenopausal women, are disproportionately affected by AD, with research indicating that estrogen may play a protective role in cognitive health. Estrogen, primarily 17β-estradiol, has been shown to modulate Aβ metabolism, reduce tau hyperphosphorylation, and enhance synaptic plasticity. These neuroprotective effects are mediated through estrogen receptors, including ERα, ERβ, and GPER, which activate signaling pathways critical for neuronal health. Epidemiological data suggest that hormone replacement therapy (HRT) in postmenopausal women may reduce the risk of AD; however, clinical results remain mixed, with some studies showing limited or even adverse effects. Understanding the complex relationship between estrogen and AD pathogenesis is crucial for advancing therapeutic interventions aimed at mitigating neurodegenerative processes, particularly in women at higher risk for AD. This review aims to synthesize current knowledge on estrogen's impact on AD and highlight potential avenues for future research and therapeutic development. This review explores the intricate relationship between estrogen signaling and AD, emphasizing the hormone's neuroprotective properties and its potential therapeutic applications.

Keywords:  Alzheimer’s disease; Estrogen; Hormone replacement therapy; Menopause

DOI:  https://doi.org/10.1007/s12035-025-05338-x
Front Public Health. 2025 ;13 1646592

The effects of Rosa damascene aromatherapy on mood and sleep: a systematic review and meta-analysis.

Shuqi Xu, Xinhua Shen, Liang Xu, Liang Xue, Ping Wu, Shiliang Wang, Xuqiang Hu.

   Background and purpose: Individuals under stress may experience a range of negative emotions and sleep disturbances. There is preliminary evidence that Rosa damascene (RD) aromatherapy is effective in improving symptoms such as negative mood and sleep. The objective of this study was to assess the effects of RD aromatherapy on anxiety, anxiety-related hemodynamic changes, depression, stress, and sleep quality, while also exploring potential moderating factors that could influence the outcome measures.
Methods: Systematic review and meta-analysis of existing randomized controlled trials on RD aromatherapy in the treatment of mood and sleep. A systematic literature search was conducted across PubMed, Web of Science, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials. We identified 28 randomized controlled trials that were pooled using a random-effects meta-analysis.
Results: The meta-analysis demonstrated that RD aromatherapy significantly alleviated anxiety symptoms (SMD = -1.31; 95% CI, -1.74 to-0.88; p < 0.001), reduced mean arterial pressure (MAP) (SMD = -0.33; 95% CI, -0.64 to-0.02; p = 0.038), and mitigated stress symptoms (SMD = -0.76; 95% CI, -1.07 to -0.44; p < 0.001), while also improving sleep quality (SMD = -2.10; 95% CI, -3.54 to -0.66; p = 0.004). The effects on depressive symptoms and pulse rate (PR) were minimal (p > 0.1).
Conclusion: Our findings suggest that RD aromatherapy can effectively reduce anxiety, improve related hemodynamic parameters, and alleviate stress symptoms, while also enhancing sleep quality. However, its effects on depressive symptoms and PR were smaller, indicating a need for larger randomized trials.
Systematic review registration: Identifier CRD42024593400, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024593400.

Keywords:  Rosa damascene aromatherapy; anxiety; depressive symptoms; sleep; systematic review and meta-analysis

DOI:  https://doi.org/10.3389/fpubh.2025.1646592
Aging Cell. 2025 Nov 18. e70294

Mitochondrial Respiratory Supercomplex Assembly Factor COX7RP Contributes to Lifespan Extension in Mice.

Kazuhiro Ikeda, Sachiko Shiba, Masataka Yokoyama, Masanori Fujimoto, Kuniko Horie, Tomoaki Tanaka, Satoshi Inoue.

  COX7RP is a critical factor that assembles mitochondrial respiratory chain complexes into supercomplexes, which is considered to modulate energy production efficiency. Whether COX7RP contributes to metabolic homeostasis and lifespan remains elusive. We here observed that COX7RP-transgenic (COX7RP-Tg) mice exhibit a phenotype characterized by a significant extension of lifespan. In addition, metabolic alterations were observed in COX7RP-Tg mice, including lower blood glucose levels at 120 min during the glucose tolerance test (GTT) without a significant difference in the area under the curve (AUC), as well as reduced serum triglyceride (TG) and total cholesterol (TC) levels. Moreover, COX7RP-Tg mice exhibited elevated ATP and nicotinamide adenine dinucleotide levels, reduced ROS production, and decreased senescence-associated β-galactosidase levels. Single-nucleus RNA-sequencing (snRNA-seq) revealed that senescence-associated secretory phenotype genes were downregulated in old COX7RP-Tg white adipose tissue (WAT) compared with old WT WAT, particularly in adipocytes. This study provides a clue to the role of mitochondrial respiratory supercomplex assembly factor COX7RP in resistance to aging and longevity extension.

Keywords:  lifespan; metabolism; mitochondria; supercomplex; white adipose tissue

DOI:  https://doi.org/10.1111/acel.70294
Nutr J. 2025 Nov 18. 24(1): 175

Effects of supplementation with two probiotic strains (Lactobacillus helveticus and Bifidobacterium longum) on hormonal status, oxidative stress, and clinical symptoms in women with polycystic ovary syndrome: a randomized clinical trial.

Mahsa Shirani, Mohammad Bagherniya, Omid Sadeghi, Hatav Ghasemi Tehrani, Mohammad Hadi Eskandari, Manoj Sharma, Gholamreza Askari.

  Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women. This study investigates the impact of 8-week supplementation with two probiotic strains, Lactobacillus helveticus and Bifidobacterium longum, on hormonal status, oxidative stress, and clinical symptoms in women with PCOS. Conducted as a double-blind, placebo-controlled, randomized clinical trial, the research involved 90 women with PCOS from Shahid Beheshti Hospital, Isfahan, Iran. Serum markers were assessed before and after the intervention. After adjusting for baseline values and confounding variables, the 8-week supplementation with two probiotic strains resulted in a significant increase in sex hormone binding globulin (24.39; 95% CI (15.23,33.55) vs. -11.99; 95% CI (-20.12, -3.86) nmol/L, P < 0.001), total antioxidant capacity (125.53; 95% CI (53.78,197.28) vs. -42.90; 95% CI (-78.32, -7.48) nmol/mL, P = 0.002) and Superoxide dismutase activity (0.19; 95% CI (0.09,0.30) vs. -0.11; 95% CI (-0.18, -0.04) U/mL, P < 0.001), in the intervention group compared to the placebo. While free androgen index (-57.05; 95% CI (-80.33, -33.76) vs. 49.86; 95% CI (28.81,70.92), P < 0.001), C-reactive protein (-0.50; 95% CI (-0.95, -0.04) vs. 0.05; 95% CI (-0.39,0.50), P = 0.046), and malondialdehyde levels (- 23.69; 95% CI (-30.02, -17.35) vs. -2.70; 95% CI (-9.19,3.77), P < 0.001), significantly decreased in the intervention group compared to the placebo. Furthermore, testosterone total levels showed a decreasing trend in the intervention group, although the between-group changes were not statistically significant after baseline value and other confounders adjustment (-3.37; 95% CI (-11.85, 5.11) vs. 6.48; 95% CI (3.43, 9.53) ng/dL, P = 0.08). Regarding clinical symptoms, including acne, alopecia, and hirsutism, the between-group changes were insignificant (P > 0.05). In conclusion, these findings suggest that 8 weeks of probiotic supplementation may alleviate oxidative stress, modulate certain hormonal factors, and reduce inflammation in women with PCOS. Trial registration, the current study was registered in the Iranian Registry of Clinical Trials on 30 March 2024 (ID: IRCT20121216011763N62) ( https://irct.behdasht.gov.ir/trial/76067 ). https://irct.behdasht.gov.ir/trial/76067 .

Keywords:  Inflammation; Oxidative stress; Polycystic ovary syndrome; Probiotics; RCT

DOI:  https://doi.org/10.1186/s12937-025-01240-3
Theriogenology. 2025 Nov 03. pii: S0093-691X(25)00470-4. [Epub ahead of print]251 117744

Docosahexaenoic acid enhances porcine oocyte maturation via AMP-mediated improvement of mitochondrial function and energy metabolism.

Yongjin Lee, Jun-Hyeong Kim, Nayoung Ko, Hyoung-Joo Kim, Kyungmin Kwak, Hyunil Kim, Joohyun Shim.

  AMP-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis that critically regulates oocyte maturation. A previous study indicates that 25 μM docosahexaenoic acid (DHA) improves energy metabolism and developmental competence during porcine oocyte in vitro maturation (IVM), demonstrating that its effects could be mediated by AMPK activation since AMPK plays a pivotal role in energy metabolism and homeostasis maintenance. This study aimed to investigate whether the effects of DHA during porcine oocyte IVM are mediated by AMPK activation. To this end, the effect of AMPK activity on oocyte maturation and developmental competence was evaluated in four experimental groups: control, DHA-treated, AMPK inhibitor (10 μM compound C; CC)-treated, and co-treatment with DHA and the inhibitor. Immunofluorescence assays showed that phosphorylated AMPK increased following DHA treatment and decreased with CC treatment during porcine oocyte IVM. Further, expression analyses of AMPK downstream target genes revealed that genes positively regulated by AMPK activity were upregulated, whereas that of the gene suppressed by AMPK activity was downregulated; CC treatment exhibited the opposite pattern. Importantly, co-treatment with DHA and CC partially restored these changes. In addition, AMPK inhibition impaired oocyte maturation, mitochondrial function, ATP content, and embryonic development, while increasing apoptosis in blastocysts. DHA mitigated these detrimental effects. Collectively, these results demonstrate that DHA effectively modulates AMPK signaling during porcine oocyte IVM, thereby improving mitochondrial function and energy metabolism and ultimately enhancing oocyte quality and developmental potential.

Keywords:  AMP-activated protein kinase; Docosahexaenoic acid; In vitro maturation; Mitochondria; Porcine

DOI:  https://doi.org/10.1016/j.theriogenology.2025.117744
Medicine (Baltimore). 2025 Oct 31. 104(44): e45519

Causal effects of dietary antioxidants on epigenetic age: A two-sample Mendelian randomization study.

Chunlan Huang, Gaofeng Zeng, Kebin Zhan, Jingsong Chen, Shao Ouyang, Qilin Ou, Bo Wang, Yang Liu.

  Oxidative stress is one of the leading causes of aging and aging-related diseases. However, there is no conclusive evidence on whether dietary antioxidants can decelerate epigenetic age in human. A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal associations between dietary antioxidants intake and epigenetic age. Summary-level data about 4 dietary antioxidants (vitamin A, vitamin C, vitamin E and carotene) and 4 epigenetic age measures (HannumAge, Intrinsic epigenetic age acceleration [IEAA], GrimAge and PhenoAge) were respectively got from FinnGen Project Database and a meta-analysis of 28 genome-wide association studies (GWAS) involving 34,710 European participants. Inverse variance weighted (IVW) was used as the main method to evaluate causal estimates complemented by other 4 methods (Weighted median, MR-Egger, Weighted mode and Simple mode). Genetically predicted dietary vitamin C was associated with decreased HannumAge (IVW: beta = -1.1988, P = .0014; weighted median: beta = -1.3342, P = .0112). IVW method found that dietary vitamin C was marginally associated with decreased GrimAge (beta = -0.768, P = .0504), other 4 methods did not find significant association between dietary vitamin C and GrimAge, but the effect direction was similar to that by IVW. There was no significant association of dietary vitamin C with IEAA and PhenoAge. MR analyses found no significant effects of vitamin A, vitamin E and carotene on 4 epigenetic age measures. In total, the study suggested that dietary vitamin C may potentially decrease epigenetic age measured by HannumAge. Further studies are needed to assess the effect of dietary antioxidants on aging and aging-related diseases, and explore related mechanisms.

Keywords:  Mendelian randomization study; biological age; dietary antioxidants; epigenetic age; vitamin C

DOI:  https://doi.org/10.1097/MD.0000000000045519
Theriogenology. 2025 Nov 13. pii: S0093-691X(25)00482-0. [Epub ahead of print]251 117756

Taurine promotes porcine oocyte maturation and embryonic development by reducing oxidative stress and enhancing energy metabolism.

Fenglei Chen, Haoxiang Wang, Yuan Liu, Qi Liu, Sheng Yang, Zhiyu Ma, Yu-Guo Yuan.

  Taurine (Tau), as a feed additive, is widely used to improve the reproductive performance of pigs. However, the effects and the underlying molecular mechanisms of Tau on in vitro maturation (IVM) of porcine oocytes and embryonic development remain insufficiently elucidated. In the current study, different doses of Tau were supplemented to the porcine oocyte IVM medium. The results showed that 50 μg/mL Tau significantly promoted cumulus cell expansion and increased the rate of oocyte maturation. Tau also significantly increased the rates of cleavage and blastocyst formation after parthenogenetic activation. DCFH-DA staining results showed that Tau significantly decreased reactive oxygen species (ROS) level. qPCR results showed that Tau significantly increased the mRNA levels of antioxidant genes (CAT, SOD1, SOD2, PRDX2, and GPX1). Furthermore, JC-1 staining revealed that Tau significantly improved mitochondrial distribution and enhanced mitochondrial membrane potential (ΔΨm). Fluo-4 AM staining showed an increase in intracellular Ca2+ concentration. Consistent with the energy metabolism findings, qPCR results showed that Tau significantly increased the mRNA levels of energy metabolism genes (NOX4 and COX2). In addition, qPCR results showed that Tau significantly increased the mRNA levels of genes (TAUT, IP3R1, and NRF2) in the TAUT/Ca2+/NRF2 pathway. In conclusion, Tau could reduce oxidative stress and improve energy metabolism to promote porcine oocyte maturation, at least partly, via the TAUT/Ca2+/NRF2 signaling pathway.

Keywords:  Energy metabolism; Oocyte maturation; Oxidative stress; Pig; Taurine

DOI:  https://doi.org/10.1016/j.theriogenology.2025.117756
J Biochem Mol Toxicol. 2025 Dec;39(12): e70619

Pharmacological Stimulation of GPER Reverses Mitochondrial Dysfunction in the Hearts of Ovariectomized Type 2 Diabetic Rats.

Nahlah Fahad-Alreshidi, Refaat A Eid, Abdullah M K Albloshi, Saud S Alharbi, Sultan Mohammed Alanazi, Thamer Alsufayan, Musaad B Alsahly, Mirwais Ramozi.

  Postmenopausal diabetic women face an increased risk of cardiovascular diseases due to estrogen deficiency and metabolic dysfunction. Mitochondrial calcium homeostasis is essential for the viability and energy production of cardiomyocytes; however, the regulation of this process in estrogen-deficient diabetic hearts is not well understood. This study aimed to explore the effects of activating the G protein-coupled estrogen receptor 1 (GPER) on cardiac mitochondrial calcium regulation via the mitochondrial calcium uniporter (MCU) in ovariectomized rats with type 2 diabetes (OVX-T2D). T2D was induced using a high-fat diet combined with a single dose of streptozotocin (30 mg/kg). The animals were divided into three groups: OVX, OVX + T2D, and OVX + T2D treated with the GPER agonist G1. Our findings indicate that GPER activation significantly increased MCU expression in the heart, mediated by the cAMP/PKA/CREB signaling cascade. This increase was associated with enhanced activity of tricarboxylic acid (TCA) cycle enzymes (PDH and α-KGDH) and improved mitochondrial ATP production. Additionally, G1 treatment reduced oxidative stress markers (MDA) and increased the activity of antioxidant enzymes (SOD), suggesting a better mitochondrial redox balance. Notably, GPER stimulation also suppressed caspase-3 expression, indicating a reduction in apoptosis within cardiac tissue. These results demonstrate that GPER activation restores mitochondrial calcium uptake and enhances mitochondrial function in the diabetic postmenopausal heart. This study highlights a novel regulatory mechanism where GPER enhances cardiac mitochondrial resilience through MCU upregulation and related metabolic and antiapoptotic pathways. Targeting GPER may emerge as a promising therapeutic strategy for alleviating diabetic cardiomyopathy in postmenopausal women.

Keywords:  GPER; cardiovascular diseases; mitochondrial calcium uniporter; oxidative stress; type 2 diabetes

DOI:  https://doi.org/10.1002/jbt.70619
Phytother Res. 2025 Nov 17.

Effects of Ashwagandha on Reproductive Health: A Systematic Review of Sex-Specific Hormonal and Fertility Outcomes.

Debajyoti Roy, Maitrayee Ghosh, Dipan Roy, Nitin Sharma, Rohit Bhatia, Naresh Kumar Rangra.

  Reproductive health is a major component of overall well-being, which is regulated by various factors like nutrition, stress and lifestyle; all of these in turn influence fertility and sexual function. Ideal reproductive health requires constant upkeep in individuals of both males and females, with natural products like ashwagandha gaining significant attention for their potential advantages. Various studies are exploring the effect of ashwagandha in the reproductive systems of both males and females. These studies are emphasizing some specific parameters like polycystic ovary syndrome, stress-induced menstrual irregularities in the case of the female reproductive system and sperm count and quality in the case of the male reproductive system. In order to study the impact of ashwagandha on the reproductive system, we conducted a systematic review involving a search of major databases like MEDLINE/PubMed, Web of Science, Scopus, Science Direct, and Google Scholar, following PRISMA guidelines. Our review included a detailed analysis of preclinical and clinical research articles that evaluated the role of ashwagandha in improving reproductive health and sexual dysfunction. This study specifically looked at its impact on the reproductive system. The findings of this study indicate that ashwagandha has the potential to improve sexual health. It can also serve as a therapeutic agent in certain reproductive disorders due to its antioxidant nature. In conclusion, ashwagandha appears to be a promising natural adjunct to the enhancement of reproductive health; however, more study is needed to understand its long-term effects and dosing more fully.

Keywords:  PCOS; ashwagandha; fertility; reproductive health; sexual health; sperm quality

DOI:  https://doi.org/10.1002/ptr.70128
Res Sq. 2025 Oct 01. pii: rs.3.rs-7697256. [Epub ahead of print]

Epigenetic Aging and Treatment Response to Semaglutide in the SLIM LIVER Study.

Michael Corley, Alina Pang, Douglas Kitch, Amy Kantor, Fred Sattler, Pablo Belaunzaran-Zamudio, Todd Brown, Alan Landay, Jordan Lake, Kristine Erlandson.

Background: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), improves metabolic health and reduces liver fat in people with HIV (PWH) and metabolic dysfunction-associated steatotic liver disease (MASLD). Whether changes in epigenetic aging biomarkers reflect these clinical benefits remains unknown. Methods: We conducted a post hoc analysis of the SLIM LIVER study (ACTG A5371), a 24-week, single-arm trial of semaglutide (1.0 mg weekly) in PWH and MASLD. Epigenetic aging was assessed at baseline and 24 weeks using DNA methylation-based epigenetic clocks: DunedinPACE (pace of aging), PCGrimAge (mortality risk), and PCDNAmTL (methylation-derived telomere length). Participants were stratified by change in epigenetic markers (decrease vs. increase); clinical responses were compared across anthropometric, metabolic, and physical function outcomes. Results: We observed a stable pace of aging was maintained over 24 weeks (n=41) with a median change of DunedinPACE of +0.018 (IQR: -0.023 to +0.053), PCDNAmTL (median -0.006 kb; IQR: -0.073 to +0.054), and PCGrimAge (median +0.54 years; IQR: -0.33 to +1.26). Seventeen (41.5%) showed a decrease in DunedinPACE with significantly greater reductions in liver fat ( p = 0.024) and improved gait speed ( p = 0.081), corresponding to a ~0.8 day (minimum, -0.0048) to ~19.5 days (maximum, -0.116) deceleration. Participants with increased PCDNAmTL (n=20) similarly demonstrated significantly greater improvements in gait speed ( p = 0.012). No significant clinical associations were observed with changes in PCGrimAge. Conclusions: These findings provide preliminary evidence that semaglutide may modulate epigenetic age biomarkers, with DunedinPACE and PCDNAmTL tracking improvements in hepatic and physical function. Integration of epigenetic biomarkers into future trials may enhance gerotherapeutic precision by identifying individuals most likely to benefit from GLP-1RA therapy and by enabling minimally invasive monitoring of biological aging. Trial Registration: ClinicalTrials.gov ID: NCT04216589.

DOI: https://doi.org/10.21203/rs.3.rs-7697256/v1
Can J Psychiatry. 2025 Nov 18. 7067437251394363

The Canadian Network for Mood and Anxiety Treatments Task Force Recommendations for the Use of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplants in Adults With Major Depressive Disorder: Recommandations du Groupe de travail du Réseau canadien pour le traitement des troubles de l'humeur et de l'anxiété (Canadian Network for Mood and Anxiety Treatments, CANMAT) concernant l'utilisation des probiotiques, des prébiotiques, des symbiotiques et de la transplantation de microbiote fécal chez les adultes atteints de trouble dépressif majeur.

Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce

  BackgroundApproximately one-third of adults with major depressive disorder (MDD) experience limited response or intolerable side effects with existing pharmacotherapies. As such, innovative treatments targeting novel biological pathways are under investigation. One promising area of research is the gut microbiome and its influence on mood through the microbiota-gut-brain axis. Clinical studies have begun evaluating microbiome-targeted interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) as potential treatments for MDD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to evaluate the evidence for microbiome-targeted interventions in adults with MDD and to provide updated clinical recommendations.MethodsA systematic review of randomized controlled trials (RCTs) and meta-analyses was conducted, assessing interventions such as probiotics, prebiotics, synbiotics, and FMT in adults with MDD. The CANMAT methodology was used to determine levels of evidence and treatment line recommendations, which were presented in a question-and-answer format.ResultsTwenty-three RCTs and eight meta-analyses were included. Probiotics have been the most extensively studied and have demonstrated modest improvements in depressive symptoms, particularly when used in an adjunctive manner. However, recent high-quality trials yielded mixed results. Evidence for prebiotics and FMT was limited and inconclusive, while synbiotics were assessed in only one small RCT. Most interventions were well tolerated, with few serious adverse events.ConclusionsProbiotics may be cautiously considered as third-line adjunctive treatments for MDD, though findings remain inconsistent. There is currently insufficient evidence to recommend prebiotics, synbiotics, or FMT in clinical practice. Further large-scale, well-controlled trials are needed to clarify efficacy, safety, and optimal patient subgroups.

Keywords:  CANMAT guidelines; adjunctive treatments; fecal microbiota transplantation; gut–brain axis; major depressive disorder; mental health interventions; microbiome-based therapies; probiotics; psychobiotics; systematic review

DOI:  https://doi.org/10.1177/07067437251394363
Sci Adv. 2025 Nov 21. 11(47): eaea7460

Mitochondrial NAD+ gradient sustained by membrane potential and transport.

Shivansh Goyal, Scott N Lyons, Xiaolu A Cambronne.

SLC25A51 is required for the replenishment of free nicotinamide adenine dinucleotide (oxidized form) (NAD+) into mammalian mitochondria. However, it is not known how SLC25A51 imports this anionic molecule to sustain elevated NAD+ concentrations in the matrix. Understanding this would reveal regulatory mechanisms used to maintain critical bioenergetic gradients for cellular respiration, oxidative mitochondrial reactions, and mitochondrial adenosine triphosphate (ATP) production. In this work, mutational analyses and localized NAD+ biosensors revealed that the mitochondrial membrane potential (ΔΨm) works in concert with charged residues in the carrier's inner pore to enable sustained import of NAD+ against its electrochemical gradient into the matrix. Dissipation of the ΔΨm or mutation of select residues in SLC25A51 led to equilibration of NAD+ from the matrix. Corroborating data were obtained with the structurally distinct mitochondrial NAD+ carrier from Saccharomyces cerevisiae (ScNdt1p) and mitochondrial ATP transport suggesting a shared mechanism of charge compensation and electrogenic transport in these mitochondrial carrier family members.

DOI: https://doi.org/10.1126/sciadv.aea7460
Biogerontology. 2025 Nov 20. 27(1): 8

Potential dietary geroprotectors and their impact on key mechanisms of aging.

Alexey Moskalev, Oksana Veselova.

  Aging involves progressive accumulation of molecular and cellular damage, leading to functional decline and increased susceptibility to age-related diseases. Natural low-molecular-weight geroprotectors are substances of plant and food origin capable of modulating key mechanisms of aging. Based on current scientific data, sixteen fundamental mechanisms of aging are analyzed, and compounds from food that demonstrate potential in slowing age-related changes are presented. Special attention is paid to the mechanisms of action of these substances at the molecular and cellular levels, as well as their availability in common food products. This review summarizes the current understanding of the interaction between natural nutrients and fundamental aging processes and opens perspectives for developing dietary strategies for healthy longevity.

Keywords:  Dietary compounds; Geroprotectors; Healthspan; Longevity; Molecular mechanisms

DOI:  https://doi.org/10.1007/s10522-025-10355-3