bims-mistre Biomed News
on Mito stress
Issue of 2025–07–20
twenty papers selected by
Ellen Siobhan Mitchell, MitoQ



  1. Foods. 2025 Jun 23. pii: 2193. [Epub ahead of print]14(13):
      In neurons, mitochondria generate energy through ATP production, thereby sustaining the high energy demands of the central nervous system (CNS). Mitochondrial dysfunction within the CNS was implicated in the pathogenesis and progression of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, often involving altered mitochondrial dynamics like fragmentation and functional impairment. Accordingly, mitochondrial targeting represents an alternative therapeutic strategy for the treatment of these disorders. Current standard drug treatments present limitations due to adverse effects associated with their chronic use. Therefore, in recent years, nutraceuticals, natural compounds exhibiting diverse biological activities, have garnered significant attention for their potential to treat these diseases. It has been shown that these compounds represent safe and easily available sources for the development of innovative therapeutics, and by modulating mitochondrial function, nutraceuticals offer a promising approach to address neurodegenerative pathologies. We referred to approximately 200 articles published between 2020 and 2025, identified through a focused search across PubMed, Google Scholar, and Scopus using keywords such as "nutraceutical," "mitochondrial dysfunction," and "neurodegenerative diseases. The purpose of this review is to examine how mitochondrial dysfunction contributes to the genesis and progression of neurodegenerative diseases. Also, we discuss recent advances in mitochondrial targeting using nutraceuticals, focusing on their mechanisms of action related to mitochondrial biogenesis, fusion, fission, bioenergetics, oxidative stress, calcium homeostasis, membrane potential, and mitochondrial DNA stability.
    Keywords:  antioxidants; mitochondrial dysfunction; neurodegenerative diseases; nutraceutical; oxidative stress
    DOI:  https://doi.org/10.3390/foods14132193
  2. Cell Signal. 2025 Jul 09. pii: S0898-6568(25)00393-6. [Epub ahead of print]135 111978
      Among the numerous immune signal transduction pathways in the human body, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has attracted much attention due to its crucial role in sensing DNA within cells. In this article, we summarize the relationships between some phenomena of aging and the cGAS-STING pathway, including autophagy dysfunction and mitochondrial dysfunction, chronic inflammation and Chromosome instability and micronucleus DNA formation, and the roles of the cGAS-STING pathway in neurodegenerative diseases related to aging, neurological infections, and neuroimmune diseases. Finally, we analyze the potential therapeutic strategies of drugs that specifically inhibit the cGAS-STING pathway, such as cGAS inhibitors, Cyclic GMP-AMP (cGAMP) inhibitors, STING inhibitors and mitochondrial protectants. By introducing various diseases and their possible treatment options, this review deeply analyzes the impact of the cGAS-STING pathway on the aging process and neurological diseases, and explores its role in aging and neurological diseases as well as its potential therapeutic prospects.
    Keywords:  Aging; Innate immunity; Neurological diseases; Therapeutic application; cGAS-STING
    DOI:  https://doi.org/10.1016/j.cellsig.2025.111978
  3. Int J Mol Sci. 2025 Jul 04. pii: 6439. [Epub ahead of print]26(13):
      Despite decades of research, the pathophysiology of preeclampsia (PE) and polycystic ovary syndrome (PCOS) remains poorly understood. Notably, no new FDA-approved treatments for PE have emerged in over 50 years. PCOS, a common endocrine disorder, increases a woman's risk of developing PE. Both conditions share overlapping mechanisms, including insulin resistance, chronic inflammation, endothelial dysfunction, and oxidative stress. While physiological levels of reactive oxygen species (ROS) are essential for reproduction, excess ROS contributes to cellular and mitochondrial damage. This review will assess current evidence linking oxidative stress and mitochondrial dysfunction to the development of PCOS and PE, explore their shared mechanisms, and evaluate emerging therapeutic interventions. Ultimately, a comprehensive understanding of these shared mechanisms may inform strategies for early prediction, prevention, and the treatment of PE and PCOS.
    Keywords:  antioxidants; endothelial dysfunction; insulin resistance; mitochondria; oxidative stress; polycystic ovary syndrome; preeclampsia; pregnancy
    DOI:  https://doi.org/10.3390/ijms26136439
  4. Int J Mol Sci. 2025 Jun 28. pii: 6233. [Epub ahead of print]26(13):
      Insulin resistance (IR) frequently develops in women with polycystic ovary syndrome (PCOS), an endocrinological disorder typified by hyperandrogenaemia, erratic menstrual cycles, and the presence of multiple cysts in the ovaries. It results in elevated androgen production contributing to the clinical manifestations of the syndrome including associated co-morbidities such as obesity and type 2 diabetes (T2D). Mounting data suggest the involvement of free fatty acids, reactive oxygen species (ROS) signalling, and mitochondrial dysfunction with IR. In recent years, numerous reports have suggested that mitochondrial dysregulation is associated with the pathogenesis of PCOS. Increased ROS, mutations/variants in mitochondrial DNA (mtDNA), and the altered expression of nuclear-related mitochondrial genes in insulin-resistant women with PCOS provide sufficient evidence for mitochondrial dysfunction as one of the factors contributing to PCOS pathogenesis. Despite the advancements in the field of interconnecting links between mitochondrial dysfunction, IR, and PCOS, various underlying mechanisms needs to be elucidated. Advancements in therapeutic interventions showed promising results in improving mitochondrial functions and IR in PCOS pathogenesis, including evolving mitochondrial transfer approaches that may improve in vitro fertilisation (IVF) outcomes in obese and insulin-resistant women with PCOS in future.
    Keywords:  ROS; hyperandrogenism; insulin resistance; mitochondrial dysfunction; polycystic ovary syndrome
    DOI:  https://doi.org/10.3390/ijms26136233
  5. Int J Mol Sci. 2025 Jun 27. pii: 6203. [Epub ahead of print]26(13):
      Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder characterized by memory loss and cognitive decline. In addition to its two major pathological hallmarks, extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs), recent evidence highlights the critical roles of mitochondrial dysfunction and neuroinflammation in disease progression. Aβ impairs mitochondrial function, which, in part, can subsequently trigger inflammatory cascades, creating a vicious cycle of neuronal damage. Estrogen receptors (ERs) are widely expressed throughout the brain, and the sex hormone 17β-estradiol (E2) exerts neuroprotection through both anti-inflammatory and mitochondrial mechanisms. While E2 exhibits neuroprotective properties, its mechanisms against Aβ toxicity remain incompletely understood. In this study, we investigated the neuroprotective effects of E2 against Aβ-induced mitochondrial dysfunction and neuroinflammation in primary cortical neurons, with a particular focus on the role of AMP-activated protein kinase (AMPK). We found that E2 treatment significantly increased phosphorylated AMPK and upregulated the expression of mitochondrial biogenesis regulator peroxisome proliferator-activated receptor gamma coactivator-1 α (PGC-1α), leading to improved mitochondrial respiration. In contrast, Aβ suppressed AMPK and PGC-1α signaling, impaired mitochondrial function, activated the pro-inflammatory nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), and reduced neuronal viability. E2 pretreatment also rescued Aβ-induced mitochondrial dysfunction, suppressed NF-κB activation, and, importantly, prevented the decline in neuronal viability. However, the pharmacological inhibition of AMPK using Compound C (CC) abolished these protective effects, resulting in mitochondrial collapse, elevated inflammation, and cell death, highlighting AMPK's critical role in mediating E2's actions. Interestingly, while NF-κB inhibition using BAY 11-7082 partially restored mitochondrial respiration, it failed to prevent Aβ-induced cytotoxicity, suggesting that E2's full neuroprotective effects rely on broader AMPK-dependent mechanisms beyond NF-κB suppression alone. Together, these findings establish AMPK as a key mediator of E2's protective effects against Aβ-driven mitochondrial dysfunction and neuroinflammation, providing new insights into estrogen-based therapeutic strategies for AD.
    Keywords:  AMPK; Alzheimer’s disease; Amyloid-β; NF-κB; estradiol; mitochondria; neuroinflammation; neuroprotection
    DOI:  https://doi.org/10.3390/ijms26136203
  6. J Cell Mol Med. 2025 Jul;29(13): e70714
      Acute alcoholism commonly targets the myocardium, triggering acute alcoholic cardiomyopathy (ACM). Strong evidence suggested that mitochondrial dysfunction-induced myocardial oxidative stress is involved in the subcellular pathogenesis of acute ACM. We investigated whether astaxanthin (AST), an antioxidant lutein carotenoid, prevents acute ACM and explored the underlying mechanisms. C57BL/6J mice were used to model ethanol-induced ACM and were treated with AST (100 mg/kg/day) alongside the autophagy inhibitor, 3-methyladenine (10 mg/kg/day). Cardiac function, heart pathology, cardiac hypertrophy, cardiomyocyte apoptosis, oxidative stress and mitochondrial function were evaluated, respectively in response to ethanol and/or AST. The in vivo study showed that ethanol-induced cardiac dysfunction, morphological injury, cardiomyocyte apoptosis and oxidative stress were mitigated by AST. AST's anti-apoptotic effects against ethanol were confirmed in vitro. Ethanol-induced cardiac apoptosis is closely associated with mitochondrial dysfunction which was attenuated by AST characterised by inhibiting fission and promoting fusion, as well as maintaining stable mitochondrial membrane potential, increased ATP production, enhanced biogenesis and restored mitophagy. Autophagy inhibition suppressed AST-induced myocardial protection, indicating that myocardial mitophagy mediates AST effects. The present study demonstrates that AST induces cardiac protection against acute ACM by improving cardiac function, reducing pathological changes, and inhibiting oxidative stress, inflammation and apoptosis through preserved myocardial mitophagy-mediated mitochondrial homeostasis.
    Keywords:  acute alcoholic cardiomyopathy; astaxanthin; mitochondrial homeostasis; mitophagy; oxidative stress
    DOI:  https://doi.org/10.1111/jcmm.70714
  7. bioRxiv. 2025 May 09. pii: 2025.05.04.652087. [Epub ahead of print]
      A coordinated response to stress is crucial for promoting the short- and long-term health of an organism. The perception of stress, frequently through the nervous system, can lead to physiological changes that are fundamental to maintaining homeostasis. Activating the response to low oxygen, or hypoxia, extends healthspan and lifespan in C. elegans . However, despite some positive impacts, negative effects of the hypoxic response in specific tissues prevent translation of their benefits in mammals. Thus, it is imperative to identify which components of this response promote longevity. Here, we interrogate the cell-nonautonomous hypoxic response signaling pathway. We find that HIF-1-mediated signaling in ADF serotonergic neurons is both necessary and sufficient for lifespan extension. Signaling through the serotonin receptor SER-7 in the GABAergic RIS interneurons is necessary in this process. Our findings also highlight the involvement of additional neural signaling molecules, including the neurotransmitters tyramine and GABA, and the neuropeptide NLP-17, in mediating longevity effects. Finally, we demonstrate that oxygen- and carbon-dioxide-sensing neurons act downstream of HIF-1 in this circuit. Together, these insights develop a circuit for how the hypoxic response cell-nonautonomously modulates aging and suggests valuable targets for modulating aging in mammals.
    DOI:  https://doi.org/10.1101/2025.05.04.652087
  8. Neuromolecular Med. 2025 Jul 16. 27(1): 51
      Neurodegenerative diseases consist of a group of progressive disorders characterized by the gradual decline in the structure or function of neurons, which ultimately results in neuronal death. The occurrence and societal effects of these disorders have been consistently rising, presenting considerable public health challenges globally. Multiple interconnected pathways, including oxidative stress, neuroinflammation, nitrosative stress, and apoptosis, drive their progression. NOX-induced ROS disrupts neuronal function, impairs mitochondrial activity, and triggers lipid peroxidation, contributing to neuronal death. Activation of the TLR-4/MAPK/NF-κB pathway triggers neuroinflammation and NLRP3 inflammasome activation. This inflammasome-driven inflammation accelerates neuronal injury and death. Moreover, reduced estrogen receptor expression weakens neuronal defenses, impairing synaptic function, thereby worsening neurodegeneration. Neurodegenerative diseases continue to be without a cure, as existing treatments focus on alleviating symptoms and modifying the disease. Due to their intricate and multifactorial pathophysiology, there is a pressing need for agents capable of targeting multiple pathological mechanisms to effectively combat these disorders. Various phytomolecules have shown promise in tackling different neurodegenerative diseases by modulating key molecular targets. Equol (4',7-isoflavandiol) is a metabolite of daidzein, a soy isoflavone present in soybeans and various other plant sources. Equol has shown significant promise in combating neurodegeneration by modulating mediators involved in oxidative stress, neuroinflammation, nitrosative stress, and apoptosis. Key signaling molecules influenced by equol include TLR-4, MAPKs, NLRP3 inflammasome, ROS, and inflammatory mediators, among others. Considering equol's ability to modulate these signaling mediators, this review explores the mechanistic pathways through which equol confers neuroprotection.
    Keywords:  Equol; Estrogen receptors; NLRP3; NOX; Neurodegeneration; ROS; TLR-4/MAPK
    DOI:  https://doi.org/10.1007/s12017-025-08875-9
  9. Exp Gerontol. 2025 Jul 10. pii: S0531-5565(25)00154-8. [Epub ahead of print]208 112825
       BACKGROUND: Mitochondrial dysfunction is a key hallmark of aging, and blood-based biomarkers related to mitochondrial genes provide an effective means to assess ovarian aging progression. In this study, we aimed to explore the role of mitochondrial dysfunction-related genetic variations in determining the natural age at menopause (ANM) by applying both Mendelian randomization (MR) and summary data-based Mendelian randomization (SMR) approaches, complemented by experimental validation in animal models.
    METHODS: Summary statistics on ANM, gene expression, DNA methylation, and protein abundance quantitative trait loci (eQTL, mQTL, pQTL) were obtained from public databases. Genetic variations associated with mitochondrial dysfunction were selected as instrumental variables, and SMR analysis was performed to investigate causal relationships with ANM. MR methods were also used to evaluate the causal effect of mitochondrial DNA copy number (mtDNA-CN) on ANM, with preliminary validation through animal experiments.
    RESULTS: SMR and meta-analysis results identified NSUN4 as a critical regulator of ANM at both the gene expression and DNA methylation levels. A preliminary causal relationship between reduced mtDNA-CN and increased ANM risk was found, though further validation with larger datasets is needed. Animal experiments indicated that NSUN4 levels in blood reflect ovarian function decline and may correlate with its expression in ovarian tissue.
    CONCLUSIONS: The findings suggest that NUSN4 levels detected in the blood could serve as a potential biomarker for ovarian aging. This provides new insights into the role of mitochondrial dysfunction in reproductive age-related traits and may inform future targeted interventions to slow ovarian aging.
    Keywords:  Age at natural menopause; Blood; Mendelian; Mitochondria; NSUN4; Ovarian aging
    DOI:  https://doi.org/10.1016/j.exger.2025.112825
  10. Free Radic Biol Med. 2025 Jul 10. pii: S0891-5849(25)00821-4. [Epub ahead of print]238 582-594
      Prion diseases are a group of fatal neurodegenerative disorders with no effective treatments. MitoQ, a mitochondria-targeted antioxidant, has shown promise in treating mitochondrial redox-related diseases; however, its role in prion diseases remains unclear. In this study, we demonstrate that MitoQ significantly alleviates PrP106-126-induced oxidative stress, mitochondrial dysfunction, and apoptosis in mouse neuroblastoma N2a cells. Specifically, MitoQ reduces intracellular and mitochondrial reactive oxygen species (ROS) accumulation, enhances total antioxidant capacity (T-AOC) and the glutathione (GSH)/oxidized glutathione (GSSG) ratio, restores oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and intracellular ATP levels, and prevents cytochrome c release and caspase 3 activation. Mechanistically, MitoQ downregulates dynamin-related protein 1 (DRP1) phosphorylation at Ser616 and reduces mitochondrial DRP1 accumulation, while upregulating optic atrophy 1 (OPA1), thereby improving the mitochondrial dynamics imbalance induced by PrP106-126. Notably, DRP1 overexpression or OPA1 knockdown abolishes these protective effects, resulting in persistent oxidative stress, mitochondrial dysfunction, and apoptosis. These findings suggest that MitoQ alleviates prion-induced neurodegeneration by modulating DRP1- and OPA1-mediated mitochondrial dynamics, highlighting its therapeutic potential in prion diseases.
    Keywords:  DRP1 and OPA1; MitoQ; Mitochondrial dynamics; Mitochondrial dysfunction; Oxidative stress; Prion diseases
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.07.017
  11. FASEB J. 2025 Jul 31. 39(14): e70846
      Polycystic ovary syndrome (PCOS) adversely impacts oocyte quality, underscoring effective interventions as a central focus of research. Our study demonstrates that nicotinamide mononucleotide (NMN) not only restores NAD+ homeostasis in oocytes from PCOS mice but also enhances the developmental rate of PCOS oocytes during in vitro maturation (IVM). Transcriptomic analysis and experimental validation suggest that NMN helps reverse the decline in PCOS oocyte quality by mitigating oxidative stress, improving mitochondrial function, and preserving spindle morphology. Mechanistically, we found that NMN supplementation upregulates SIRT1 expression, which responds to fluctuations in NAD+ levels through the NAD+ salvage pathway regulated by nicotinamide mononucleotide adenylyltransferase (NMNAT). In conclusion, our findings highlight the potential of NMN in improving PCOS oocyte quality, offering valuable insights for clinical PCOS treatment and the advancement of assisted reproductive technology.
    Keywords:  NAD+; NMN; NMNAT; PCOS oocyte; SIRT1
    DOI:  https://doi.org/10.1096/fj.202500921R
  12. Nutr Metab (Lond). 2025 Jul 11. 22(1): 75
       BACKGROUND: Recent research has implicated mitochondrial DNA copy number (mtDNA-CN) and Tau protein levels in the blood as potential biomarkers for early Alzheimer's disease (AD) risk assessment, correlating with metabolite profiles. However, intermediary metabolites mediating these associations remain elusive.
    METHODS: Employing a two-sample and a mediation Mendelian randomization (MR) analysis of the IEU OpenGWAS database, involving 383,476 participants from a genome-wide association study (GWAS) and an exome-wide association study (ExWAS), we identified intermediary metabolites linking mtDNA-CN and Tau.Meanwhile, the effects of mediating metabolites on HT22 cell viability and its mitochondrial morphology were also assessed in conjunction with in vitro experiments.
    RESULTS: Our study revealed an association of mtDNA-CN on Tau (OR = 3.102, 95% CI: 1.016-9.472, P = 0.047), as well as on other 31 metabolites such as 3-Hydroxybutyrate (3HB), Docosahexaenoic acid (DHA), Acetate, Albumin, Apolipoprotein A-I (APOA1), and so on. Notably, 3HB was further implicated in a relationship with Tau (OR = 6.030, 95% CI: 1.054-34.491, P = 0.043), acting as a mediator between mtDNA-CN and Tau. In vitro experiments demonstrated that 3HB positively sustained HT22 cell viability by MTT assay and mitigated mitochondrial swelling under low glucose conditions, as observed via HIS-SIM. In Western blot (WB) and quantitative real-time PCR (qPCR) assays, phosphorylation levels of Tau at serine 262 (p-Tau262) and serine 396 (p-Tau396) were tended to decline following 3HB intervention. Additionally, a positive correlation was identified between 3HB concentration and mtDNA-CN.
    CONCLUSIONS: These findings underscore the potential of 3HB as a biomarker and mediator in early AD risk assessment. Moreover, 3HB's ability to enhance cell viability, maintain mitochondrial morphology, decrease phosphorylated Tau protein expression and increase mtDNA-CN under stressful conditions, suggesting its therapeutic potential in improving the imbalance of energy metabolism in the AD brain.
    Keywords:  3-Hydroxybutyrate; HT22 cells; Mendelian randomization; Metabolites; Mitochondrial DNA copy number; Tau
    DOI:  https://doi.org/10.1186/s12986-025-00960-x
  13. J Nutr. 2025 Jul 15. pii: S0022-3166(25)00427-4. [Epub ahead of print]
      This review highlights the importance and potential beneficial effects of dietary supplements, including taurine, tauroursodeoxycholic acid (TUDCA), curcumin, coenzyme Q10 (CoQ10), creatine, and N-acetylcysteine (NAC) in the management of neurodegenerative diseases. Studies in preclinical models have consistently shown significant potential of these supplements in mitigating neurodegenerative pathology. Through a range of mechanisms targeting different molecular pathways, these supplements demonstrate therapeutic outcomes in preclinical models of such conditions such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. This review discusses published data on each of these supplements in the context of neurodegenerative diseases. It also discusses a combination therapy concept and proposes a strategy to formulate an optimal blend of these supplements. This combination approach will target key processes, including mitochondrial dysfunction, protein misfolding, neuroinflammation, and oxidative stress responsible for neurodegenerative conditions. Additionally, this review examines various models used for both the initial screening and subsequent assessment of candidate supplement combinations.
    Keywords:  Alzheimer’s Disease; Amyotrophic Lateral Sclerosis; Food Supplement; Huntington’s Disease; Neuroprotection; Parkinson’s Disease
    DOI:  https://doi.org/10.1016/j.tjnut.2025.07.004
  14. Front Physiol. 2025 ;16 1602271
       Introduction: Type 2 diabetes (T2D) is a global epidemic, and heart failure is the primary cause of premature death among T2D patients. Mitochondrial dysfunction has been linked to decreased contractile performance in diabetic heart, partly due to a disturbance in the mitochondrial capacity to supply adequate metabolic energy to contractile proteins. MOTS-c, a newly discovered mitochondrial-derived peptide, has shown promise as a therapeutic for restoring energy homeostasis and muscle function in metabolic diseases. However, whether MOTS-c therapy improves T2D heart function by increasing mitochondrial bioenergetic function remains unknown.
    Methods: Here we studied the mitochondrial bioenergetic function of heart tissues isolated from a rat model mimicking type 2 diabetes induced by a high-fat diet and low-dose streptozotocin. Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks. We employed high-resolution respirometric and fluorometric techniques to simultaneously assess mitochondrial ATP production and hydrolysis capacity, reactive oxygen species (ROS) production, and oxygen flux in cardiac tissue homogenates.
    Results: We found that untreated T2D rats had hyperglycemia, poor glucose control, and left ventricular hypertrophy relative to controls. T2D mitochondria showed decreased oxygen flux at the oxidative phosphorylation (OXP) while ROS production, ATP production and hydrolysis rates remained unchanged. Diabetic rats treated with MOTS-c showed decreased fasting glucose levels, improved glucose homeostasis, and decreased degree of cardiac hypertrophy. At the subcellular level, MOTS-c treated mitochondria showed increased OXPHOS respiration and ROS levels and decreased ATP hydrolysis rate during anoxic conditions.
    Discussion: These findings demonstrate beneficial effects of MOTS-c treatment on glucose homeostasis and suggest a useful therapeutic option for diabetic-related cardiomyopathy and mitochondrial dysfunction.
    Keywords:  ATP; MOTS-c; diabetic heart; mitochondrial respiration; reactive oxygen species
    DOI:  https://doi.org/10.3389/fphys.2025.1602271
  15. Psychogeriatrics. 2025 Jul;25(4): e70071
      This review evaluates the role of vitamins in neurodegeneration. Low levels of B vitamins have been associated with cognitive decline. B vitamins may help inhibit amyloid plaque aggregation. Vitamin D deficiency has been linked to an increased risk of cognitive impairment, correlating with Alzheimer's pathology. Vitamin E may help delay Alzheimer's disease progression and support functional abilities. In Parkinson's disease, vitamin D shows promise in reducing dopaminergic neuron loss and improving motor and cognitive outcomes. Vitamin C reduces oxidative stress and preserves neuronal integrity. Vitamin K has gained attention for its role in cognitive health, with studies suggesting that higher levels may be linked to improved cognitive performance. In conclusion, a better understanding of the translational potential of these vitamins may inform preventive and therapeutic strategies for neurodegenerative diseases. Clinicians should consider vitamin supplementation for aging-related conditions. Further studies are needed to confirm its therapeutic potential and clarify underlying mechanisms in neurodegeneration.
    Keywords:  Alzheimer's disease; cognitive impairment; neurodegeneration; neuroprotection; oxidative damage; vitamin supplementation
    DOI:  https://doi.org/10.1111/psyg.70071
  16. Front Immunol. 2025 ;16 1621759
      Age-related conditions, such as neurodegenerative disease, cancer, and autoimmune disorders, are increasingly recognized as closely linked with the gradual deterioration of the immune system. Regulatory T cells (Tregs) are a small, specialized subset of T lymphocytes that play a critical role in maintaining immune homeostasis and self-tolerance. As individuals age, Treg cells demonstrate reduced capacity to suppress some autoreactive immune responses, although they largely retain their capacity to regulate effector antiviral and antitumor immunity. Unlike conventional effector T cells (Teff), which primarily derive energy from glycolysis, Tregs rely more on mitochondrial oxidative phosphorylation to fulfill their energy requirements. This metabolic profile renders them particularly sensitive to mitochondrial dysfunction, underpinning the critical role of mitochondrial protective pathways in preserving the functional integrity of Treg cells. The mitochondrial unfolded protein response (mitoUPR) is gaining special relevance among these protective mechanisms. In this review, we examine the complex interplay between immune aging and mitochondrial dynamics, with particular emphasis on the essential role of mitoUPR in supporting Treg function. We further discuss how targeting mitochondrial stress responses may offer novel therapeutic avenues for age-related diseases characterized by Treg dysfunction.
    Keywords:  aging; cell metabolism; cellular stress; immunosenescence; oxidative stress; regulatory T-cells; unfolded protein response
    DOI:  https://doi.org/10.3389/fimmu.2025.1621759
  17. medRxiv. 2025 May 23. pii: 2025.05.22.25328181. [Epub ahead of print]
      Epigenetic clocks can predict pathological aging associated with Alzheimer's disease (AD) risk, albeit findings are mixed regarding if clocks are predictive in blood and in non-European populations. We constructed epigenetic clocks from blood methylation data in 704 older Hispanic adults and tested the association with a clinical diagnosis of AD and plasma biomarker levels. Biological age and age acceleration, the rate of biological aging, were significantly associated with sex, clinical diagnosis, and levels of eight plasma biomarkers, including P-Tau217 levels. Additionally, biomarker associations trended more significant among APOE -ε4 non-carriers. We also identified that methylation levels in CD4 and CD8 T-cell types are associated with biological aging and showed slightly stronger associations in men. We demonstrate that biological aging, in blood, in a Hispanic cohort of both demented and non-demented individuals, can stratify AD risk, predicting plasma biomarker levels even in preclinical disease.
    DOI:  https://doi.org/10.1101/2025.05.22.25328181
  18. Nutrients. 2025 Jul 04. pii: 2216. [Epub ahead of print]17(13):
      Magnesium is an essential mineral involved in hundreds of biochemical reactions, with particular relevance to maintaining neural homeostasis, modulating neurotransmitter systems, and regulating inflammatory and oxidative stress mechanisms. This comprehensive review aims to evaluate the potential role of magnesium in the pathophysiology and treatment of three prevalent neurological and psychiatric disorders-depression, migraine, and Alzheimer's disease-as well as its broader implications for cognitive health. Current research suggests that magnesium deficiency is associated with the development of depression, as magnesium influences glutamatergic and GABAergic neurotransmission, as well as the activity of the hypothalamic-pituitary-adrenal (HPA) axis, both of which play critical roles in stress responses and mood regulation. Additionally, magnesium's anti-inflammatory properties may contribute to the alleviation of depressive symptoms. In the context of migraine's pathophysiology, magnesium plays a role in regulating cerebral vascular tone, modulating the trigeminovascular system, and reducing neuronal hyperexcitability, which may explain the observed correlation between magnesium levels and the incidence of migraines. Regarding Alzheimer's disease, preclinical and epidemiological studies suggest that magnesium may contribute to modulating neurodegenerative processes and preserving cognitive function; however, due to the heterogeneity of the current findings, further longitudinal and interventional studies are necessary to determine its precise clinical relevance. This review aims to enhance the understanding of the relationship between magnesium and these disorders through a narrative review of relevant clinical studies. The findings may provide insights into the potential therapeutic applications of magnesium and guide the future directions of the research into the prevention and treatment of depression, migraine, and Alzheimer's disease and overall cognitive health.
    Keywords:  Alzheimer’s disease; HPA axis; cognitive health; depression; inflammation; magnesium; migraine; neurodegeneration; neurotransmitters; oxidative stress
    DOI:  https://doi.org/10.3390/nu17132216
  19. Nutrients. 2025 Jun 21. pii: 2068. [Epub ahead of print]17(13):
      Endometriosis is a chronic, hormone-dependent disease that affects women of reproductive age. It leads to numerous adverse clinical symptoms, which significantly impact women's quality of life. The chronic nature of the disease and its recurrence are the main reasons for the search for new, non-hormonal drugs and drug candidates, either as adjunct treatment options or alternative therapies. The catechin found in green tea, epigallocatechin gallate (EGCG), has been shown to exhibit a wide array of biological activities, which may also contribute to its potential effectiveness in treating endometriosis. The poor physicochemical stability and relatively low bioavailability of EGCG have stimulated the development of a peracetylated prodrug (pro-EGCG) and other solutions, based on nanotechnology, that would eliminate the problems with EGCG. In this review article, we summarize the studies on the effects of EGCG, pro-EGCG, and EGCG-based nanoparticles on the course of endometriosis published in the GoogleScholar and PubMed databases. Of note is the fact that the results of in vitro and animal model studies have suggested that EGCG and pro-EGCG can reduce the number of endometriosis foci and their size and volume, and they can prevent fibrosis by affecting multiple molecular factors and signaling pathways. The promising results provide a basis for using green herbal extracts for endometriosis treatment in a clinical trial. Nevertheless, it should be emphasized that the number of studies on the topic is currently very limited; further expansion in the coming years is necessary. Broad, well-designed clinical trials are also essential to validate the true potential of EGCG and related compounds in the fight against endometriosis.
    Keywords:  EGCG octaacetate; clinical trials; endometriosis; epigallocatechin-3-gallate; green tea; in vitro; in vivo; nanoparticles; prodrugs
    DOI:  https://doi.org/10.3390/nu17132068
  20. Front Cardiovasc Med. 2025 ;12 1631578
      Aging is a complex biological process characterized by a gradual decline in cellular and physiological function, increasing vulnerability to chronic diseases and mortality. It involves a set of interconnected mechanisms known as the hallmarks of aging, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, and dysregulated nutrient sensing. These processes act at molecular, cellular, and systemic levels, contributing to age-related disorders such as neurodegeneration, cardiovascular disease, and metabolic syndromes. Emerging therapeutic strategies aim to delay or reverse aging by targeting specific hallmarks. These include senolytics to eliminate senescent cells, NAD+ boosters and mitophagy inducers to improve mitochondrial health, epigenetic reprogramming, and caloric restriction mimetics such as metformin and rapamycin to modulate nutrient-sensing pathways. Advances in regenerative medicine, gene editing, and organ cross-talk modulation are also contributing to the development of personalized, multi-targeted anti-aging therapies. Integration of omics technologies and biomarker research is expected to enhance our ability to monitor biological aging and optimize interventions for healthy longevity. This review highlights the current understanding of the hallmarks of aging and explores potential treatment strategies in light of our recent findings.
    Keywords:  aging related disease; biological aging; chronic inflammation; chronological aging; senscence
    DOI:  https://doi.org/10.3389/fcvm.2025.1631578