bims-mistre 2025-09-07 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–09–07
twenty papers selected by
Ellen Siobhan Mitchell, MitoQ

Biological and translational attributes of mitochondrial DNA copy number: Laboratory perspective to clinical relevance.
The role of FGF21 in the metabolic adjustments required for exercise capacity.
Mitochondrial diagnostics reveal diffuse impairments in skeletal muscle energetics in aging mice.
Dysfunctional mitochondria in ageing T cells: a perspective on mitochondrial quality control mechanisms.
The impact of mitochondrial dysfunction on osteoarthritis cartilage: current insights and emerging mitochondria-targeted therapies.
Mechanisms of SIRT3 regulation of aging and aging-related diseases and advances in drug therapy.
FGF21 and GDF15 Act Synergistically to Regulate Systemic Metabolic Homeostasis in Mice Lacking OPA1 in Thermogenic Adipocytes.
Effects of nutrients and diet on mitochondrial dysfunction: An opportunity for therapeutic approaches in human disease.
Lipid-laden endothelial cells exhibit a transcriptomic signature linked to blood-brain barrier dysfunction, metabolic reprogramming and increased inflammation in the aging brain.
Mitochondria structurally remodel near synapses to fuel the sustained energy demands of plasticity.
Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development.
Respiratory Resilience as Form Fades: Skeletal Muscle Mitochondrial Adaptation in Aging.
Lipids Engage a Kidney-Brain GDF15 Axis to Suppress Food Intake.
The potential of mulberry (Morus alba L.) leaf extract against pro-aggregant tau-mediated inflammation and mitochondrial dysfunction.
Mechanisms of Biological Aging with Special Reference to the Skeletal Muscle.
Therapeutic strategies in traditional Chinese medicine for premature ovarian failure: Modulation of oxidative stress and autophagy-apoptosis via the AMPK/mTOR pathway.
The effect of barberry supplementation on components of metabolic syndrome: a grade assessment systematic review and meta-analysis of randomized controlled trials.
Therapeutic potential of alpha-lipoic acid on mitochondrial dynamics, oxidative/nitrosative stress, and histopathological changes in rat ulcerative colitis model.
Perceived stress and socioeconomic status differentially modulate the relationship between progesterone and cortisol reactivity to the socially evaluated cold pressor task.
Targeted energy metabolomics analysis-based mitochondrial restoration: Nutritional intervention of dairy-derived MFG-E8 synergistic with egg yolk phosphatidylcholine in skeletal muscle regeneration.

World J Methodol. 2025 Sep 20. 15(3): 102709

Biological and translational attributes of mitochondrial DNA copy number: Laboratory perspective to clinical relevance.

Deepak Parchwani, Ragini Singh, Digisha Patel.

  The mitochondrial DNA copy number (mtDNAcn) plays a vital role in cellular energy metabolism and mitochondrial health. As mitochondria are responsible for adenosine triphosphate production through oxidative phosphorylation, maintaining an appropriate mtDNAcn level is vital for the overall cellular function. Alterations in mtDNAcn have been linked to various diseases, including neurodegenerative disorders, metabolic conditions, and cancers, making it an important biomarker for understanding the disease pathogenesis. The accurate estimation of mtDNAcn is essential for clinical applications. Quantitative polymerase chain reaction and next-generation sequencing are commonly employed techniques with distinct advantages and limitations. Clinically, mtDNAcn serves as a valuable indicator for early diagnosis, disease progression, and treatment response. For instance, in oncology, elevated mtDNAcn levels in blood samples are associated with tumor aggressiveness and can aid in monitoring treatment efficacy. In neurodegenerative diseases such as Alzheimer's and Parkinson's, altered mtDNAcn patterns provide insights into disease mechanisms and progression. Understanding and estimating mtDNAcn are critical for advancing diagnostic and therapeutic strategies in various medical fields. As research continues to uncover the implications of mtDNAcn alterations, its potential as a clinical biomarker is likely to expand, thereby enhancing our ability to diagnose and manage complex diseases.

Keywords:  Aging; Cancer; Mitochondrial DNA; Mitochondrial DNA copy number; Neurodegenerative disease; Quantitative polymerase chain reaction

DOI:  https://doi.org/10.5662/wjm.v15.i3.102709
Life Sci. 2025 Aug 29. pii: S0024-3205(25)00575-2. [Epub ahead of print]380 123940

The role of FGF21 in the metabolic adjustments required for exercise capacity.

Lisa Abe, Robert Dantzer.

  Fatigue is one of the most common and persistent symptoms experienced by patients with various medical conditions. It is characterized by its enduring nature, lack of improvement after a good night's sleep, and interference with daily functioning. The mechanisms behind fatigue remain controversial. In cancer patients, inflammation and mitochondrial dysfunction appear to be the predominant contributors. Mitochondrial dysfunction results from oxidative stress and inflammation. This condition leads to the production and release of soluble mediators known as mitokines, which act in an autocrine, paracrine, and endocrine manner to help the body adapt to the changes in energy metabolism caused by mitochondrial dysfunction. The main mitokines include growth differentiation factor (GDF) 15 and fibroblast growth factor (FGF) 21. We have already gathered evidence highlighting the pivotal role of GDF15 in the behavioral fatigue that arises in response to chemotherapy. In this perspective article, we explore whether the existing knowledge about the role of FGF21 in metabolic adaptations during cellular stress positions this mitokine as a potential candidate for cancer-related fatigue. To do this, we summarize how FGF21 is produced at the level of each organ involved in energy metabolism and how its local and distant effects may influence the capacity to engage in energy-intensive activities such as physical exercise.

Keywords:  Energy metabolism; FGF21; Fatigue; Metabolic adaptations; Mitochondria; Physical activity; Physical exercise

DOI:  https://doi.org/10.1016/j.lfs.2025.123940
J Appl Physiol (1985). 2025 Sep 04.

Mitochondrial diagnostics reveal diffuse impairments in skeletal muscle energetics in aging mice.

Keon D Wimberly, Mia Y Kawaida, Abigail L Tice, Xiaoping Luo, Jacob A Lackey, Samuel Alvarez, Lan Wei-LaPierre, Russell T Hepple, Terence E Ryan.

  Aging is associated with progressive declines in skeletal muscle mass, strength, and endurance, often linked to mitochondrial dysfunction. However, a complete understanding of mitochondrial impairments during aging is lacking. Herein, we examined how biological sex and aging affect muscle function and mitochondrial energy transduction. Methods: Male and female C57BL/6 mice at 16 and 26 months of age (N=48) were assessed for physical function, muscle contractility, histology, and mitochondrial bioenergetics. Using isolated limb muscle mitochondria, we employed a diagnostic approach to evaluate respiration, redox potential, and membrane polarization under physiologically relevant energy demands. Results: Aged mice had significantly lower grip strength (P = 2.7E-09), walking speed (P = 0.024), and endurance capacity (P = 1.24E-08). Muscle mass and contractile function were also significantly lower in 26-mo. old mice regardless of sex. Mitochondrial diagnostics revealed a significant reduction (30-50%) in oxygen consumption rates across a range of energy demands and substrate conditions in both male and female 26-mo. old mice. Redox and membrane potentials were also reduced (P < 0.05) in aged mice resulting in a lower respiratory efficiency when compared to 16-mo. old mice. Notably, aged males exhibited greater mitochondrial deficits with carbohydrate substrates, while aged females showed larger declines with fatty acid substrates. Conclusion: Aging induces diffuse impairments in mitochondrial energy transduction in skeletal muscle of mice of both sexes. The application of mitochondrial diagnostics platform offers new insights into the changes in muscle mitochondria with aging and could enhance the identification of interventions for preserving mitochondrial health in aging.

Keywords:  aging; metabolism; mitochondria; muscle

DOI:  https://doi.org/10.1152/japplphysiol.00601.2025
EMBO Rep. 2025 Aug 29.

Dysfunctional mitochondria in ageing T cells: a perspective on mitochondrial quality control mechanisms.

Lin Luo, Ana Victoria Lechuga-Vieco, Clara Sattentau, Mariana Borsa, Anna Katharina Simon.

  Dysfunctional mitochondria are a hallmark of T cell ageing and contribute to organismal ageing. This arises from the accumulation of reactive oxygen species (ROS), impaired mitochondrial dynamics, and inefficient removal of dysfunctional mitochondria. Both cell-intrinsic and cell-extrinsic mechanisms for removing mitochondria and their byproducts have been identified in T cells. In this review, we explore how T cells manage mitochondrial damage through changes in mitochondrial metabolism, mitophagy, asymmetric mitochondrial inheritance, and mitochondrial transfer, highlighting the impact of these mechanisms on T cell ageing and overall organismal ageing. We also discuss current therapeutic strategies aimed at removing dysfunctional mitochondria and their byproducts and propose potential new therapeutic targets that may reverse immune ageing or organismal ageing.

Keywords:  Asymmetric Cell Division; Mitochondrial Metabolism; Mitochondrial Transfer; Mitophagy; T Cell Ageing

DOI:  https://doi.org/10.1038/s44319-025-00536-z
Bone Res. 2025 Sep 01. 13(1): 77

The impact of mitochondrial dysfunction on osteoarthritis cartilage: current insights and emerging mitochondria-targeted therapies.

Siyuan Tan, Yujun Sun, Shixun Li, Haoyu Wu, Yue Ding.

Osteoarthritis (OA) is a degenerative joint disease associated with age, prominently marked by articular cartilage degradation. In OA cartilage, the pathological manifestations show elevated chondrocyte hypertrophy and apoptosis. The mitochondrion serves as key energy supporter in eukaryotic cells and is tightly linked to a myriad of diseases including OA. As age advances, mitochondrial function declines progressively, which leads to an imbalance in chondrocyte energy homeostasis, partially initiating the process of cartilage degeneration. Elevated oxidative stress, impaired mitophagy and mitochondrial dynamics jointly contribute to chondrocyte pathology, with mitochondrial DNA haplogroups, particularly haplogroup J, influencing OA progression. Therapeutic approaches directed at mitochondria have demonstrated remarkable efficacy in treating various diseases, with triphenylphosphonium (TPP) emerging as the most widely utilized molecule. Other strategies encompass Dequalinium (DQA), the Szeto-Schiller (SS) tetrapeptide family, the KLA peptide, and mitochondrial-penetrating peptides (MPP), etc. These molecules share common properties of lipophilicity and positive charge. Through various technological modifications, they are conjugated to nanocarriers, enabling targeted drug delivery to mitochondria. Therapeutic interventions targeting mitochondria offer a hopeful direction for OA treatment. In the future, mitochondria-targeted therapy is anticipated to improve the well-being of life for the majority of OA patients. This review summarizes the link between chondrocyte mitochondrial dysfunction and OA, as well as discusses promising mitochondria-targeted therapies and potential therapeutic compounds.

DOI: https://doi.org/10.1038/s41413-025-00460-x
Gerontology. 2025 Aug 26. 1-22

Mechanisms of SIRT3 regulation of aging and aging-related diseases and advances in drug therapy.

Junye Yang, Yi Lu, Yue Zhao, Xiaobo Wang.

Sirtuin 3 (SIRT3), a NAD⁺-dependent deacetylase localized in the mitochondrial matrix, has emerged as a central regulator of aging and age-related pathologies. This review synthesizes evidence demonstrating SIRT3's tripartite anti-senescence mechanisms: 1) Enhancement of mitophagy via p53 deacetylation-mediated mitochondrial quality control, 2) Reinforcement of antioxidant defenses through SOD2/IDH2 activation, and 3) Optimization of metabolic homeostasis by coordinating fatty acid β-oxidation and glucose metabolism. In neurodegenerative models, SIRT3 ameliorates proteotoxic stress by promoting ketogenesis and reducing amyloid-β/tau pathology. SIRT3 mediates cardiovascular protection through dual modulation of fibrotic signaling cascades and nitric oxide biosynthesis. Paradoxically, SIRT3 exhibits context-dependent roles in oncology, suppressing tumor metabolism via HIF1α destabilization while potentially enabling chemoresistance through ferroptosis regulation. Within metabolic disorders, SIRT3 preserves β-cell function by neutralizing oxidative stress and SASP-driven inflammation, significantly delaying diabetes progression. Current therapeutic strategies leverage SIRT3's pleiotropic functions through natural compounds: Gastrodin (mitochondrial membrane stabilization), cocoa polyphenols (FOXO3-mediated antioxidant enhancement), and baicalein (anti-fibrotic signaling blockade). These advances position SIRT3 as a critical interface between mitochondrial energetics and systemic aging, offering a unified framework for developing precision gerotherapeutics.

DOI: https://doi.org/10.1159/000547549
Obesity (Silver Spring). 2025 Sep 02.

FGF21 and GDF15 Act Synergistically to Regulate Systemic Metabolic Homeostasis in Mice Lacking OPA1 in Thermogenic Adipocytes.

Joshua Peterson, Jayashree Jena, Ayushi Sood, Shelly Roitershtein, David Smith, Renata O Pereira.

   OBJECTIVE: Our previous studies showed that mice lacking the mitochondrial fusion protein optic atrophy 1 (OPA1 BKO) in brown adipose tissue (BAT) have high metabolic rates and are resistant to diet-induced obesity (DIO) via effects partially mediated by independent actions of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) secretion from BAT. We examined whether FGF21 and GDF15 act synergistically, contributing to the systemic metabolic adaptations reported in OPA1 BKO mice.
METHODS: We generated mice simultaneously lacking the Opa1, Fgf21, and Gdf15 genes in thermogenic adipocytes (TKO) and assessed energy homeostasis and glucose metabolism after regular chow or high-fat diet feeding.
RESULTS: Young TKO mice fed regular chow had impaired glucose tolerance, while insulin sensitivity was unchanged. Notably, combined Fgf21 and Gdf15 deletion in OPA1 BKO significantly blunted the resistance to DIO and insulin resistance observed in OPA1 BKO mice.
CONCLUSIONS: FGF21 and GDF15 act synergistically to maintain glucose homeostasis and promote resistance to DIO in mice lacking OPA1 in BAT, highlighting the potential of combined therapies using FGF21 and GDF15 for the treatment of metabolic disorders.

Keywords:  Brown Adipose Tissue; FGF21; GDF15; Mitochondrial Stress; Obesity

DOI:  https://doi.org/10.1002/oby.70004
Biomed Pharmacother. 2025 Aug 28. pii: S0753-3322(25)00687-0. [Epub ahead of print]191 118493

Effects of nutrients and diet on mitochondrial dysfunction: An opportunity for therapeutic approaches in human disease.

Lisa H Do, Renata T Da Costa, Maria E Solesio.

  Mitochondria play a crucial role in multiple cellular processes beyond the regulation of bioenergetics. These processes range from apoptosis to intracellular signaling. Accordingly, mitochondrial dysfunction has been broadly described in the etiopathology of multiple human diseases, including cancer, diabetes, and all the main neurodegenerative disorders. Therapeutic interventions aimed at modulating this dysfunction are promising for preventing and/or delaying the development of these pathologies. Recent research has highlighted the potential of dietary interventions to modulate mitochondrial physiology. In this text, we critically review the scientific literature available regarding the effects of different dietary interventions (such as caloric restriction, ketogenic diets, increased omega-3 fatty acid consumption, etc.) on some key components of mitochondrial physiology. Despite the significant advancements in the field that we present in this review, critical gaps remain regarding the molecular mechanisms that underlie the effects of these dietary interventions on mitochondrial physiology, especially under pathological conditions. Future research in this field could underscore these mechanisms, paving the road for the use of dietary interventions against mitochondrial dysfunction as valid pharmacological strategies in human disease.

Keywords:  Diet; Mitochondria; Mitochondrial physiology; Nutrients; Therapeutic approaches

DOI:  https://doi.org/10.1016/j.biopha.2025.118493
bioRxiv. 2025 Aug 28. pii: 2025.08.22.671845. [Epub ahead of print]

Lipid-laden endothelial cells exhibit a transcriptomic signature linked to blood-brain barrier dysfunction, metabolic reprogramming and increased inflammation in the aging brain.

Sarah Otu-Boakye, Duraipandy Natarajan, Bhuvana Plakkot, Ilakiya Raghavendiran, Tamas Kiss, Madhan Subramanian, Priya Balasubramanian.

Dysregulation in lipid metabolism is increasingly recognized as a key contributor to age-related diseases, including neurodegeneration and cerebrovascular dysfunction. While prior studies have largely focused on glial cells, the impact of lipid dysregulation on brain endothelial aging remains poorly understood. In this study, we conducted a secondary analysis of single-cell transcriptomic data from young and aged mouse brains, with a specific focus on endothelial cells (ECs). Our analyses revealed that aging promotes lipid droplet accumulation in brain ECs. These lipid-laden brain ECs exhibit a transcriptomic signature indicative of impaired blood-brain barrier function, increased cellular senescence, and inflammation in aging. Furthermore, lipid accumulation is associated with an altered metabolic phenotype characterized by increased fatty acid oxidation and decreased glycolysis, and impaired mitochondrial electron transport chain activity in the ECs of the aging brain. We have also validated lipid accumulation in aged ECs in vivo . Collectively, our findings indicate that lipid accumulation drives structural, functional, and metabolic impairments in the brain ECs, likely contributing to cerebrovascular aging. Understanding the mechanisms underlying lipid accumulation-induced endothelial dysfunction may offer novel therapeutic strategies for mitigating microvascular dysfunction and cognitive decline in aging.

DOI: https://doi.org/10.1101/2025.08.22.671845
bioRxiv. 2025 Aug 27. pii: 2025.08.27.672715. [Epub ahead of print]

Mitochondria structurally remodel near synapses to fuel the sustained energy demands of plasticity.

Monil Shah, Ilika Ghosh, Luca Pishos, Valentina Villani, Tristano Pancani, Ryohei Yasuda, Chao Sun, Naomi Kamasawa, Vidhya Rangaraju.

The brain is a metabolically demanding organ as it orchestrates and stabilizes neuronal network activity through plasticity. This mechanism imposes enormous and prolonged energetic demands at synapses, yet it is unclear how these needs are met in a sustained manner. Mitochondria serve as a local energy supply for dendritic spines, providing instant and sustained energy during synaptic plasticity. However, it remains unclear whether dendritic mitochondria restructure their energy production unit to meet the sustained energy demands. We developed a correlative light and electron microscopy pipeline with deep-learning-based segmentations and 3D reconstructions to quantify mitochondrial remodeling at 2 nm pixel resolution during homeostatic plasticity. Using light microscopy, we observe global increases in dendritic mitochondrial length, as well as local increases in mitochondrial area near spines. Examining the mitochondria near spines using electron microscopy, we reveal increases in mitochondrial cristae surface area, cristae curvature, endoplasmic reticulum contacts, and ribosomal cluster recruitment, accompanied by increased ATP synthase clustering within mitochondria using single-molecule localization microscopy. Using mitochondria- and spine-targeted ATP reporters, we demonstrate that the local structural remodeling of mitochondria corresponds to increased mitochondrial ATP production and spine ATP levels. These findings suggest that mitochondrial structural remodeling is a key underlying mechanism for meeting the energy requirements of synaptic and network function.

DOI: https://doi.org/10.1101/2025.08.27.672715
Cell Biol Toxicol. 2025 Sep 02. 41(1): 129

Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development.

Yao Jiang, Yonghua Shi, Meng Lv, Tao Wang, Penghao Wang, Xiaolong Yuan, Fei Gao, Bin Ma.

  Ovarian aging significantly contributes to the decline of the female reproductive system, adversely affecting fertility and endocrine homeostasis. To address the challenges posed by reproductive aging, natural products have shown promising preventive and therapeutic effects. Here, we investigated the beneficial effects of natural compound celastrol on ovarian development and aging, together with its underlying mechanisms. We found that celastrol administration at a concentration of 3 mg/kg promoted follicle development in young mice and enhanced porcine oocyte maturation, while regulating granulosa cell proliferation and apoptosis. In 12-month-old mice (equivalent to middle-aged adults), celastrol exhibited similar beneficial effects. Transcriptomic analysis revealed that differentially expressed genes post-celastrol treatment were associated with steroid biosynthesis, estrogen signaling pathways, type 2 diabetes, insulin secretion, meiosis, and apoptosis. Additionally, insulin receptor substrate 1 (IRS1), an adapter protein in insulin signaling, was shown to advance puberty in young mice and to facilitate oocyte maturation. Overexpression of IRS1 in oocytes promoted follicular development and oocyte maturation, resulting in enhanced steroid hormone levels, whereas IRS1 knockdown inhibited these processes. Our findings indicate that celastrol may regulate ovarian development and aging by modulating IRS1 expression and its related pathways, suggesting celastrol as a novel small-molecule compound targeting IRS1, and offering new perspectives for potential therapeutic strategies against reproductive aging and infertility.

Keywords:  Celastrol; Follicular development; IRS1; Natural product; Oocyte maturation; Ovarian aging

DOI:  https://doi.org/10.1007/s10565-025-10079-7
Am J Physiol Endocrinol Metab. 2025 Sep 02.

Respiratory Resilience as Form Fades: Skeletal Muscle Mitochondrial Adaptation in Aging.

John Noone.



Keywords:  Mitochondria; aging; flux control ratios; morphology; skeletal muscle

DOI:  https://doi.org/10.1152/ajpendo.00369.2025
Diabetes. 2025 Aug 28. pii: db250174. [Epub ahead of print]

Lipids Engage a Kidney-Brain GDF15 Axis to Suppress Food Intake.

Ameth N Garrido, Song-Yang Zhang, Kyla Bruce, Charmaine S H Lai, Zeyu Yang, Melissa T Wang, Tony K T Lam.

ARTICLE HIGHLIGHTS: Upper small intestine lipid infusion increases kidney, hepatic, and plasma growth differentiation factor 15 (GDF15) levels in chow but not high-fat rats. Upper small intestine lipid infusion lowers food intake in chow but not high-fat rats. Knockdown of kidney Gdf15 negates lipids to increase plasma GDF15 and lower feeding. Knockdown of GDNF family receptor α-like (Gfral) in the area postrema negates lipid anorectic effect.

DOI: https://doi.org/10.2337/db25-0174
Neurochem Int. 2025 Aug 26. pii: S0197-0186(25)00115-9. [Epub ahead of print]190 106042

The potential of mulberry (Morus alba L.) leaf extract against pro-aggregant tau-mediated inflammation and mitochondrial dysfunction.

Te-Hsien Lin, Pei-Hsuan Tseng, I-Cheng Chen, Chung-Yin Lin, Ming-Chung Lee, Kuo-Hsuan Chang, Guey-Jen Lee-Chen, Chiung-Mei Chen.

  In Alzheimer's disease (AD), Tau aggregates trigger microglial activation to release inflammatory factors and cause mitochondrial dysfunction, oxidative stress, and neuronal damage. With abundant potent antioxidants, mulberry (Morus alba L.) leaf extract has the potential to treat diseases associated with neuroinflammation, mitochondrial dysfunction, and oxidative stress. This study examined the neuroprotective effects of a mulberry leaf extract against pro-aggregant Tau-mediated inflammation and mitochondrial dysfunction in SH-SY5Y cells expressing the ΔK280 Tau repeat domain (TauRD). His-tagged ΔK280 TauRD fibrils prepared from E. coli activated BV-2 microglia, as revealed by their altered morphology, increased nitric oxide production, and elevated ionized calcium binding adaptor molecule 1 (IBA1) and major histocompatibility complex 2 (MHCII) expression. The mulberry leaf extract suppressed the production of pro-inflammatory mediators, including NO, IL-1β, IL-6, and TNF-α, and the expression of NLR family pyrin domain-containing 3 (NLRP3) and caspase-1 (CASP1) in ΔK280 TauRD fibril-stimulated BV-2 cells. Application of conditioned media collected from ΔK280 TauRD fibril-activated BV-2 cells induced cellular inflammation in ΔK280 TauRD-DsRed-expressing SH-SY5Y cells. The mulberry leaf extract protected these cells by suppressing lactate dehydrogenase (LDH) release, caspase-3 activity, NLR family pyrin domain-containing 1 (NLRP1), CASP1, IL-1β, IL-6, TNF-α, and reactive oxygen species as well as by enhancing neurite outgrowth. In addition, mulberry leaf extract increased mitochondrial membrane potential, lowered mitochondrial superoxide levels, and increased superoxide dismutase 2 (SOD2), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), and nuclear factor erythroid 2-related factor 2 (NRF2) levels in SH-SY5Y cells. In conclusion, mulberry leaf extract displayed neuroprotective effects by exerting anti-inflammatory and antioxidative activities to ameliorate pathological Tau-mediated mitochondrial dysfunction in a human Tau cell model. The results of this study support the notion that the mulberry leaf extract is a potential disease-modifying therapeutic agent for AD.

Keywords:  Alzheimer's disease; Mulberry leaf extract; Neuroinflammation; Neuroprotection; Tau

DOI:  https://doi.org/10.1016/j.neuint.2025.106042
Adv Exp Med Biol. 2025 ;1478 317-342

Mechanisms of Biological Aging with Special Reference to the Skeletal Muscle.

Sataro Goto, Zsolt Radak.

  Model animals for aging research are described referring to the definition of biological aging, emphasizing importance of post-mitotic or slowly dividing cells in multicellular organisms. Selected theories of the molecular mechanisms of biological aging are examined in general including historical backgrounds on the genome instability theory of aging, free radical or oxidative stress theory of aging, mitochondrial theory of aging, error catastrophe theory of aging or translational error theory of aging, altered protein theory of aging or proteostasis theory of aging, and epigenetic theory of aging. The special relevance of these theories to the skeletal muscle aging are referred in each section.

Keywords:  Aging theories; Definition of aging; Mechanisms of aging

DOI:  https://doi.org/10.1007/978-3-031-88361-3_13
Biosci Trends. 2025 Aug 29.

Therapeutic strategies in traditional Chinese medicine for premature ovarian failure: Modulation of oxidative stress and autophagy-apoptosis via the AMPK/mTOR pathway.

Wenli Cao, Siling Liu, Leifang Zhang, Xiayan Fu, Haiyang Li, Feijun Ye, Jialu Bei, Chunzhi Ren, Yanping Ni, Jun Zhu, Ling Wang.

  Premature ovarian failure (POF), also referred to as premature ovarian insufficiency (POI), is a multifactorial reproductive endocrine disorder characterized by amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels before the age of 40. Emerging evidence links its pathogenesis to oxidative stress and dysregulation of the autophagy-apoptosis balance in ovarian cells. Excessive accumulation of reactive oxygen species (ROS) impairs mitochondrial function in oocytes, while aberrant autophagy and granulosa cell apoptosis accelerate the depletion of primordial follicles. The AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway serves as a critical nexus between energy metabolism, oxidative stress, and cell survival. Traditional Chinese medicine (TCM), with its multi-component and multi-target characteristics, has demonstrated unique advantages in modulating the AMPK/mTOR pathway to restore ovarian function. This review synthesizes recent findings on single herbs, classical formulas, and non-pharmacological therapies (acupuncture and moxibustion). Mechanistic studies have revealed that these interventions can activate AMPK, inhibit mTOR overactivation, enhance Nrf2-mediated antioxidant defenses, reduce ROS production, and rebalance autophagy and apoptosis via pathways such as PI3K/Akt and SIRT1/p53. By aligning stage-specific regulation of AMPK/mTOR signaling with the TCM principle of syndrome differentiation, this integrative approach provides theoretical guidance for precise, personalized treatment to optimize multi-target strategies for POF management.

Keywords:  AMPK/mTOR; Nrf2; PI3K/Akt; acupuncture; apoptosis; autophagy; moxibustion; oxidative stress; premature ovarian failure; traditional Chinese medicine

DOI:  https://doi.org/10.5582/bst.2025.01193
J Health Popul Nutr. 2025 Aug 30. 44(1): 313

The effect of barberry supplementation on components of metabolic syndrome: a grade assessment systematic review and meta-analysis of randomized controlled trials.

Xiu Zhang, Qion Lou, Sho Liou, Xiaoshan Wang.

   OBJECTIVE: Polyphenol-rich foods, such as barberry, improve cardiovascular risk factors, but evidence remains inconsistent. Therefore, this systematic review and meta-analysis were carried out to assess the effects of barberry supplementation on components of metabolic syndrome in adults.
METHOD: A comprehensive literature search of Web of Science, Embase, PubMed, Scopus, and the Cochrane Library was conducted up to July 2025. We included randomized clinical trials that examined the effect of barberry on one of the components of metabolic syndrome in this meta-analysis. Weighted mean differences (WMD) were pooled using a random-effects model.
RESULTS: Eleven studies published between 2012 and 2023 were included, comprising 718 participants. Barberry supplementation significantly reduced weight (WMD = - 1.48 kg; 95% CI: - 2.94 to - 0.02), systolic blood pressure (WMD: - 9.84; 95% CI: - 17.36 to - 2.31), diastolic blood pressure (WMD: - 11.31; 95% CI: - 19.63 to - 3.00), total cholesterol (WMD = - 17.90 mg/dL; 95% CI: - 32.99 to - 2.81), low-density lipoprotein cholesterol (WMD = - 11.38 mg/dL; 95% CI: - 21.35 to - 1.40), and triglyceride (WMD = - 23.63 mg/dL; 95% CI: - 35.58 to - 11.68), FBS (WMD = - 16.69 mg/dL; 95% CI: - 30.46 to - 2.93), HOMA-IR (WMD = - 0.95; 95% CI: - 1.79 to - 0.12), insulin (WMD = - 1.70 mU/L; 95% CI: - 2.33 to - 1.08). It also increased high-density lipoprotein cholesterol levels (WMD = 2.46 mg/dL; 95% CI: 0.61 to 4.31). However, no significant effect was found for glycated hemoglobin (WMD = - 0.72%; 95% CI: - 1.85 to 0.40) or body mass index (WMD = - 0.28 kg/m2; 95% CI: - 0.59 to 0.03).
CONCLUSION: Barberry supplementation elicits modest but significant improvements in key components of metabolic syndrome, including blood pressure, weight, lipid profile, and glycemic indices. These results support its potential as an adjunctive dietary intervention for managing metabolic health.

Keywords:  Barberry; Blood pressure; Glycemic indices; Lipid profile; Meta-analysis; Obesity

DOI:  https://doi.org/10.1186/s41043-025-01067-y
Inflammopharmacology. 2025 Sep 01.

Therapeutic potential of alpha-lipoic acid on mitochondrial dynamics, oxidative/nitrosative stress, and histopathological changes in rat ulcerative colitis model.

İrem Taner, Nur Banu Bal, Saadet Özen Akarca Dizakar, Veysel Bay, Mürşide Ayşe Demirel.

  Ulcerative colitis is a chronic inflammatory disease affecting the gastrointestinal tract. In addition to treatments aimed at healing inflammation and tissue damage, addressing redox imbalance and mitochondrial dysfunction is crucial. The aim of the present study is to investigate the effects of Alpha-Lipoic Acid (ALA), either alone or in combination with mesalamine, on oxidative/nitrosative stress, mitochondrial dynamics, and histopathological changes in a rat model of ulcerative colitis. Rats were divided into Control (C), Ulcerative Colitis (UC), Mesalamine (M), ALA, and Mesalamine + Alpha-lipoic acid (M + ALA) groups. Colitis was induced by intrarectal administration of 4% acetic acid. The disease activity index was the highest in the UC group and the lowest in the M + ALA group among the treatment groups. Macroscopic scores in the UC, M, and ALA groups were significantly higher compared to the C group. The oxidative stress index was the highest in the UC group, with significantly elevated levels compared to the C, ALA, and M + ALA groups. The nitrotyrosine level was also highest in the UC group and significantly elevated compared to the C, M, ALA, and M + ALA groups. Dynamin-related protein 1, Mitofusin-2, and PTEN-induced putative kinase 1 proteins showed significant increases in the UC group compared to the C group. In contrast, these protein levels were significantly reduced in the M + ALA group compared to the UC group. Histopathological scoring in the UC group increased, and ALA administration significantly ameliorated these parameters. Our results indicate that ALA has beneficial effects on increased oxidative stress, impaired mitochondrial dynamics, and altered histopathological scores in the rat colitis model.

Keywords:  Alpha lipoic acid; Mitochondrial dynamics; Oxidative/nitrosative stress; Rat; Ulcerative colitis

DOI:  https://doi.org/10.1007/s10787-025-01918-4
Psychoneuroendocrinology. 2025 Aug 18. pii: S0306-4530(25)00302-6. [Epub ahead of print]181 107579

Perceived stress and socioeconomic status differentially modulate the relationship between progesterone and cortisol reactivity to the socially evaluated cold pressor task.

Eleanor H Goulden, Charleen J Gust, Angela D Bryan, Erik L Knight.

  The research on how progesterone shapes physiologic responses to acute stress has yielded inconsistent results. This heterogeneity may be partially attributable to progesterone's effects being shaped by psychosocial stress, whether in the form of stress exposure, such as that associated with low subjective socioeconomic status (SES), or perceived stress. Though one's preexisting levels of stress exposure and perceived stress have been identified as impacting the cortisol response to acute psychosocial stress as well, like progesterone, prior results have been mixed. Therefore, the goal of this study was to examine how subjective SES and perceived stress interact with progesterone to predict cortisol reactivity to an in-lab psychosocial stressor. Undergraduate cisgender women (n = 66) were exposed to the Socially-Evaluated Cold Pressor Task, with salivary hormones measured before, immediately, and + 20 min after the task. Results showed a main effect of progesterone on cortisol responsivity such that those low in progesterone produced a blunted cortisol response and those high in progesterone produced the expected cortisol spike (b = 0.012, t(64) = 3.67, p < 0.001). SES (0.004, t(62) = 2.39, p = 0.02) and PSS scores (b = 0.001, t(62) = 2.13, p = 0.037) moderated this effect. Among those high in progesterone, lower levels of SES were correlated with blunted cortisol responses and, separately, higher levels of perceived stress were correlated with heightened cortisol responses. Our finding that self-reported SES and perceived stress modulate the relationship between progesterone and acute stress reactivity can further our understanding of how and why progesterone's relationship to certain health outcomes differs between individuals. Elucidating the relationship between progesterone and stress reactivity may have implications for understanding individual differences in the mental health effects of the menstrual cycle and progestin-based contraceptives.

Keywords:  Acute Stress; Cortisol; Menstrual Cycle; Progesterone; SECPT; SES

DOI:  https://doi.org/10.1016/j.psyneuen.2025.107579
Int J Biol Macromol. 2025 Aug 28. pii: S0141-8130(25)07772-4. [Epub ahead of print]323(Pt 2): 147215

Targeted energy metabolomics analysis-based mitochondrial restoration: Nutritional intervention of dairy-derived MFG-E8 synergistic with egg yolk phosphatidylcholine in skeletal muscle regeneration.

Kaifang Guan, Xiaolin Liu, Rongmei Liu, Ran Xiao, Weihong Lu, Ying Ma, Rongchu Wang, Tianjiao Niu.

  This study explores the therapeutic potential and mechanistic basis of a novel dairy-egg derived nutritional intervention-combining milk fat globule-epidermal growth factor 8 (MFG-E8) and egg yolk phosphatidylcholine (PC)-against dexamethasone (Dex)-induced skeletal muscle atrophy in aged rats. Specifically, we aimed to determine whether MFG-E8 + PC co-supplementation could mitigate muscle atrophy, improve mitochondrial function and elucidate the underlying mechanisms involving energy metabolism. By integrating targeted energy metabolomics, we demonstrate that the synergistic action of MFG-E8 and PC alleviates muscle atrophy in aged rats by restoring mitochondrial function and energy metabolism. Dietary supplementation with MFG-E8 + PC significantly reversed Dex-induced reductions in body mass and swimming endurance, while ameliorating histopathological features of muscle atrophy. Mechanistically, MFG-E8 + PC upregulated tricarboxylic acid (TCA) cycle intermediates (e.g., citrate, α-ketoglutarate, malate) and enhanced glycolysis and oxidative phosphorylation (OXPHOS) by reactivating rate-limiting enzymes (hexokinase, phosphofructokinase-1, citrate synthase). This metabolic regulation was linked to increased mitochondrial biogenesis via the AMPK/PGC-1α/Nrf1 axis and elevated expression of respiratory chain complexes. Notably, the dairy-egg synergy mitigated oxidative stress by restoring mitochondrial membrane potential and reducing reactive oxygen species, highlighting its dual role in energy metabolism and antioxidant protection. These findings position MFG-E8 and PC as promising functional food components for muscle health, offering a dietary strategy to combat age- or stress-related muscle wasting through mitochondrial-targeted nutritional intervention.

Keywords:  Dairy-derived MFG-E8; Energy metabolism; Mitochondria function; Nutritional intervention; Targeted energy metabolomics

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.147215