bims-mistre Biomed News
on Mito stress
Issue of 2025–06–22
eighteen papers selected by
Ellen Siobhan Mitchell, MitoQ
  1. Metabolic breakdown: Linking insulin resistance and mitochondrial dysfunction to neurodegeneration in Alzheimer's disease.
  2. Cardiolipin Remodeling in Cardiovascular Diseases: Implication for Mitochondrial Dysfunction.
  3. Interaction between mitochondrial oxidative stress and myocardial fibrosis in the context of diabetes.
  4. Role of mitochondria in physiological activities, diseases, and therapy.
  5. Mitochondrial innate immune signaling in skeletal muscle adaptation to exercise.
  6. Effects of atmospherically relevant PM2.5 on skeletal muscle mitochondria: a review of damage mechanisms and potential of exercise interventions.
  7. Ergothioneine as a Functional Nutraceutical: Mechanisms, Bioavailability, and Therapeutic Implications.
  8. Fasting the mitochondria to prevent neurodegeneration: the role of ceramides.
  9. Synaptic mitochondria in aging and neurodegenerative diseases: unraveling their functional decline and vulnerability.
  10. Low-Glucose Culture Conditions Bias Neuronal Energetics Towards Oxidative Phosphorylation.
  11. Mitochondrial deoxyguanosine kinase depletion induced ROS causes melanocyte stem cell exhaustion and hair greying.
  12. Type 2 diabetes and depression via microvascular dysfunction, neurodegeneration, inflammation, advanced glycation end products (AGEs), arterial stiffness.
  13. Mitochondrial dysfunction in the regulation of aging and aging-related diseases.
  14. Improvement on mitochondrial energy metabolism of Codonopsis pilosula (Franch.) Nannf. polysaccharide.
  15. Unveiling the role of NAD glycohydrolase CD38 in aging and age-related diseases: insights from bibliometric analysis and comprehensive review.
  16. Exploring the Effects of Oxidative Stress on Female Reproductive Function: The Role of Antioxidant Supplementation.
  17. Gut sulfide metabolism modulates behavior and brain bioenergetics.
  18. Hormone therapy and insulin resistance in non-diabetic postmenopausal women: a systematic review and meta-analysis.
  1. Neural Regen Res. 2025 Jun 19.
    Metabolic breakdown: Linking insulin resistance and mitochondrial dysfunction to neurodegeneration in Alzheimer's disease.
    Simona Lanzillotta, Lucrezia Romana Rolfi, Barbara Zulli, Eugenio Barone.
       ABSTRACT: The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways, with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline. Insulin resistance impairs neuronal metabolism and synaptic function, fostering neurodegeneration as observed in Alzheimer's disease and Down syndrome. Indeed, Down syndrome, characterized by the triplication of the APP gene, represents a valuable genetic model for studying early-onset Alzheimer's disease and accelerated aging. Building on the link between metabolic dysfunctions and neurodegeneration, innovative strategies addressed brain insulin resistance as a key driver of cognitive decline. Intranasal insulin has shown promise in improving cognition in early Alzheimer's disease and type 2 diabetes, supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration. However, insulin-based therapies risk desensitizing insulin signaling, potentially worsening the disease. Incretins, particularly glucagonlike peptide 1 receptor agonists, offer neuroprotective benefits by enhancing insulin sensitivity, metabolism, and synaptic plasticity while reducing oxidative distress and neuroinflammation. This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance, mitochondrial dynamics (including their roles in energy metabolism), and oxidative distress regulation, as these are pivotal in both Alzheimer's disease and Down syndrome. By addressing these interconnected mechanisms, innovative treatments may emerge for both metabolic and neurodegenerative disorders.
    Keywords:  Alzheimer’s disease; Down syndrome; aging; brain insulin resistance; energy metabolism; glucagon-like peptide 1; incretins; insulin; mitochondria; neurodegeneration
    DOI:  https://doi.org/10.4103/NRR.NRR-D-25-00144
  2. Acta Physiol (Oxf). 2025 Jul;241(7): e70073
    Cardiolipin Remodeling in Cardiovascular Diseases: Implication for Mitochondrial Dysfunction.
    Huijie Zhang, Fengzhi Yu, Zhenjun Tian, Dandan Jia.
       AIM: Mitochondrial dysfunction is pivotal in both the development and progression of cardiovascular diseases (CVDs), though its exact mechanisms remain unclear. Cardiolipin (CL), a key mitochondrial phospholipid, is involved in various mitochondrial functions, including dynamics, membrane integrity, oxidative phosphorylation, mitochondrial DNA maintenance, and mitophagy. Due to enzyme limitations in the CL biosynthesis pathway, premature CL undergoes remodeling to acquire the proper acyl content for its function. Disruption in CL composition leads to mitochondrial dysfunction, contributing significantly to CVDs. The purpose of this review is to explore the role of CL remodeling in the mechanism of mitochondrial dysfunction that occurs in CVDs.
    METHODS: This review examines CL's critical role in mitochondrial function, the consequences of CL deficiencies in CVDs, and the impact of mutations or deficiencies in CL remodeling enzymes-tafazzin (TAZ), Acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1), and Monolysocardiolipin acyltransferase (MLCLAT1)-on CL homeostasis, mitochondrial function, and CVDs pathogenesis. Emerging CL-targeted therapies are also reviewed.
    RESULTS: Proper CL function is crucial for mitochondrial health and cardioprotection. Pathological CL remodeling due to mutations or deficiencies in TAZ, ALCAT1, or MLCLAT1, drives mitochondrial dysfunction and accelerates CVDs progression. Based on these insights, current CL-based therapeutic strategies are also summarized, including precision medicine/gene therapy, targeted pharmacotherapy, and dietary interventions.
    CONCLUSION: Targeting CL may represent a promising clinical therapeutic strategy for CVDs.
    Keywords:  ALCAT1; cardiolipin remodeling; cardiovascular diseases; mitochondrial dysfunction; tafazzin
    DOI:  https://doi.org/10.1111/apha.70073
  3. Front Endocrinol (Lausanne). 2025 ;16 1596436
    Interaction between mitochondrial oxidative stress and myocardial fibrosis in the context of diabetes.
    Pu-Hua Zhang, Nuo-Nan Li, Xiang Gu, Chun-Xia Zhou, Zhen-Zhen Jiang, Xian-Jun Luo, Hong-Wen Zhu, Xiao-Yong Zhu.
      Diabetes represents a global chronic health issue and has emerged as a crucial risk factor for cardiovascular diseases (CVD). Myocardial fibrosis (MF), which often accompanies diabetes, plays a pivotal role in the progression of cardiac dysfunction and heart failure (HF). Recent research has highlighted mitochondrial oxidative stress (OS) as a fundamental mechanism driving MF in diabetic conditions. Elevated blood glucose levels and metabolic imbalances lead to mitochondrial impairments, which in turn cause an excessive buildup of reactive oxygen species (ROS), culminating in OS. This OS not only inflicts direct damage on myocardial cells but also facilitates the proliferation of myocardial fibroblasts and collagen accumulation through the activation of specific signaling pathways, thus intensifying MF. Furthermore, MF itself intensifies mitochondrial OS, creating a vicious cycle that ultimately impairs myocardial structure and function. Thus, a thorough understanding of the interaction between mitochondrial OS and MF in diabetes is crucial for identifying effective therapeutic targets and enhancing the early diagnosis and intervention strategies for diabetic cardiomyopathy.
    Keywords:  diabetes; drug therapy; interaction; mitochondrial oxidative stress; myocardial fibrosis; signaling pathways
    DOI:  https://doi.org/10.3389/fendo.2025.1596436
  4. Mol Biomed. 2025 Jun 19. 6(1): 42
    Role of mitochondria in physiological activities, diseases, and therapy.
    Lilin Wang, Xiaoting Zhou, Tianqi Lu.
      Mitochondria are generally considered essential for life in eukaryotic organisms because they produce most of the energy or adenosine triphosphate (ATP) needed by the cell. Beyond energy production, it is now widely accepted that mitochondria also play a pivotal role in maintaining cellular homeostasis and signaling. The two core processes of mitochondrial dynamics, fission and fusion, serve as crucial foundations for maintaining mitochondrial morphology, distribution, and quantity, thereby ensuring cellular homeostasis. Mitochondrial autophagy (mitophagy) ensures the selective degradation of damaged mitochondria, maintaining quality control. Mitochondrial transport and communication further enhance their role in cellular processes. In addition, mitochondria are susceptible to damage, resulting in dysfunction and disruption of intracellular homeostasis, which is closely associated with the development of numerous diseases. These include mitochondrial diseases, neurodegenerative diseases, cardiovascular diseases (CVDs) and stroke, metabolic disorders such as diabetes mellitus, cancer, infectious diseases, and the aging process. Given the central role of mitochondria in disease pathology, there is a growing need to understand their mechanisms and develop targeted therapies. This review aims to provide a comprehensive overview of mitochondrial structure and functions, with a particular focus on their roles in disease development and the current therapeutic strategies targeting mitochondria. These strategies include mitochondrial-targeted antioxidants, modulation of mitochondrial dynamics and quality control, mitochondrial genome editing and genetic therapy, and mitochondrial transplantation. We also discuss the challenges currently facing mitochondrial research and highlight potential future directions for development. By summarizing the latest advancements and addressing gaps in knowledge, this review seeks to guide future research and clinical efforts in the field of mitochondrial medicine.
    Keywords:  Cancer; Mitochondria; Mitochondrial diseases; Mitochondrial homeostasis; Therapy
    DOI:  https://doi.org/10.1186/s43556-025-00284-5
  5. Trends Endocrinol Metab. 2025 Jun 12. pii: S1043-2760(25)00119-5. [Epub ahead of print]
    Mitochondrial innate immune signaling in skeletal muscle adaptation to exercise.
    Jin Ma, Annie Yujin Son, Youlim Son, Ping-Yuan Wang, Paul M Hwang.
      Exercise-induced inflammation is regarded as a response to muscle damage from mechanical stress, but controlled immune signaling can be beneficial by promoting metabolic adaptation which, for example, decreases obesity and lowers the risk of diabetes. In addition to oxidative metabolism, mitochondria play a central role in initiating innate immune signaling. We review recent work that has identified the cGAS-STING-NF-κB signaling pathway, activated by the downregulation of mitochondrial proteins CHCHD4 and TRIAP1, as mediating skeletal muscle adaptation to exercise training as well as potentially promoting cellular resilience to environmental stresses. Notably, CHCHD4 haploinsufficiency prevents obesity in aging mice; therefore, this innate immune signaling pathway could be targeted to achieve some of the health benefits of exercise.
    Keywords:  CHCHD4; TRIAP1; exercise; fiber type; innate immunity; metabolism; mtDNA; obesity
    DOI:  https://doi.org/10.1016/j.tem.2025.05.004
  6. Front Public Health. 2025 ;13 1615363
    Effects of atmospherically relevant PM2.5 on skeletal muscle mitochondria: a review of damage mechanisms and potential of exercise interventions.
    Yi Ding, Qiliang Wan, Wenduo Liu.
      This study aims to explore the multifaceted impacts and mechanisms of fine particulate matter (PM2.5) exposure on skeletal muscle mitochondria. Evidence suggests that PM2.5 can penetrate the respiratory barrier and enter the circulatory system, spreading throughout the body and causing significant damage to the morphology, quantity, and function of skeletal muscle mitochondria. This is manifested by a decline in oxidative phosphorylation efficiency and mitochondrial dysfunction. Meanwhile, PM2.5 exposure induces excessive production of reactive oxygen species, triggering oxidative stress responses that impair mitochondrial dynamic regulation. This further disrupts the balance of glucose and lipid metabolism in skeletal muscle, exacerbating the development of metabolic diseases. The review underscores the systemic effects on skeletal muscle following mitochondrial dysfunction after PM2.5 exposure and the preventive and treatment potential of exercise.
    Keywords:  exercise; fine dust; mitochondrial function; particulate matter; skeletal muscle
    DOI:  https://doi.org/10.3389/fpubh.2025.1615363
  7. J Nutr Biochem. 2025 Jun 18. pii: S0955-2863(25)00169-X. [Epub ahead of print] 110006
    Ergothioneine as a Functional Nutraceutical: Mechanisms, Bioavailability, and Therapeutic Implications.
    Rony Abdi Syahputra, Amer Ahmed, Asriadi, Arnika Gloria Br Barus, Sintia Karina Putri, Michle William Tan, Qhelen Mayline Chandra, Brathennovic, Yumiko Angiosaki, Felice Chrismary Lu, Davini Clister, Arya Tjipta Prananda, Princella Halim, Rosy Iara Maciel de Azambuja Ribeiro, Fahrul Nurkolis, Aminah Dalimunthe.
      Ergothioneine (EGT), a naturally occurring sulfur-containing antioxidant, has gained significant attention owing to its potent cytoprotective, anti-inflammatory, and neuroprotective properties. As a dietary-derived compound predominantly found in mushrooms, EGT exhibits remarkable stability and bioavailability, facilitated by a specific ergothioneine transporter that is highly expressed in mammalian tissues. Its ability to scavenge reactive oxygen and nitrogen species effectively mitigates oxidative stress, which is a key factor in the pathogenesis of various chronic diseases, including cardiovascular disorders, neurodegenerative conditions, and cancer. Emerging evidence has highlighted the role of EGT in modulating key signaling pathways involved in inflammation, apoptosis, and cellular homeostasis, suggesting its potential as a therapeutic agent. Clinical and preclinical studies have indicated its involvement in metabolic regulation, endothelial protection, and attenuation of neurodegeneration, further reinforcing its significance as a functional nutraceutical agent. This review provides a comprehensive analysis of EGT, including its biosynthesis, dietary sources, absorption mechanisms, and metabolism, and elucidates its therapeutic potential and mechanistic underpinnings for disease prevention and management. By summarizing recent advances in EGT research, this review aims to guide future investigations and support its broader application in clinical and nutritional sciences.
    Keywords:  Antioxidant; Disease Prevention; Ergothioneine; Nutraceutical; Oxidative Stress
    DOI:  https://doi.org/10.1016/j.jnutbio.2025.110006
  8. Front Neurosci. 2025 ;19 1602149
    Fasting the mitochondria to prevent neurodegeneration: the role of ceramides.
    Luis Armando Valenzuela-Ahumada, Octavio Fabián Mercado-Gómez, Rubi Viveros-Contreras, Rosalinda Guevara-Guzmán, Alberto Camacho-Morales.
      Neurodegenerative diseases affect up to 349.2 million individuals worldwide. Preclinical and clinical advances have documented that altered energy homeostasis and mitochondria dysfunction is a hallmark of neurological disorders. Diet-derived ceramides species might target and disrupt mitochondria function leading to defective energy balance and neurodegeneration. Ceramides as bioactive lipid species affect mitochondria function by several mechanism including changes in membrane chemical composition, inhibition of the respiratory chain, ROS overproduction and oxidative stress, and also by activating mitophagy. Promising avenues of intervention has documented that intermittent fasting (IF) is able to benefit and set proper energy metabolism. IF is an eating protocol that involves alternating periods of fasting with periods of eating which modulate ceramide metabolism and mitochondria function in neurons. This review will address the detrimental effect of ceramides on mitochondria membrane composition, respiratory chain, ROS dynamics and mitophagy in brain contributing to neurodegeneration. We will focus on effect of IF on ceramide metabolism as a potential avenue to improve mitochondria function and prevention of neurodegeneration.
    Keywords:  ceramides; intermittent fasting; microglia; mitophagy; neurodegeneration
    DOI:  https://doi.org/10.3389/fnins.2025.1602149
  9. Neural Regen Res. 2025 Jun 19.
    Synaptic mitochondria in aging and neurodegenerative diseases: unraveling their functional decline and vulnerability.
    Karina A Cicali, Angie K Torres, Cheril Tapia-Rojas.
       ABSTRACT: Aging is a physiological and complex process produced by accumulative age-dependent cellular damage, which significantly impacts brain regions like the hippocampus, an essential region involved in memory and learning. A crucial factor contributing to this decline is the dysfunction of mitochondria, particularly those located at synapses. Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites. In contrast, non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply. Both pools of mitochondria differ in their form, proteome, functionality, and cellular role. The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics, transport, and quality control. However, synaptic mitochondria are particularly vulnerable to age-associated damage, characterized by oxidative stress, impaired energy production, and calcium dysregulation. These changes compromise synaptic transmission, reducing synaptic activity and cognitive decline during aging. In the context of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's, the decline of synaptic mitochondrial function is even more pronounced. These diseases are marked by pathological protein accumulation, disrupted mitochondrial dynamics, and heightened oxidative stress, accelerating synaptic dysfunction and neuronal loss. Due to their specialized role and location, synaptic mitochondria are among the first organelles to exhibit dysfunction, underscoring their critical role in disease progression. This review delves into the main differences at structural and functional levels between synaptic and nonsynaptic mitochondria, emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration. These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration. This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria, highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.
    Keywords:  aging; hippocampus; memory; mitochondria; synaptic mitochondria
    DOI:  https://doi.org/10.4103/NRR.NRR-D-24-01571
  10. J Neurochem. 2025 Jun;169(6): e70125
    Low-Glucose Culture Conditions Bias Neuronal Energetics Towards Oxidative Phosphorylation.
    Sarpras Swain, David M Roberts, Saad Chowdhry, Ryan Durbin, Reece Boyd, Juli Petereit, Robert Renden.
      Neurons are almost exclusively cultured in media containing glucose at much higher concentrations than found in the brain. To test whether these "standard" hyperglycemic culture conditions affect neuronal respiration relative to near-euglycemic conditions, we compared neuronal cultures grown with minimal glial contamination from the hippocampus and cortex of neonatal C57BL/6NCrl mice in standard commercially available media (25 mM Glucose) and in identical media with 5 mM glucose. Neuronal growth in both glucose concentrations proceeded until at least 14 days in vitro, with similar morphology and synaptogenesis. Neurons grown in high glucose were highly dependent on glycolysis as their primary source of ATP, measured using ATP luminescence and cellular respirometry assays. In contrast, neurons grown in 5 mM glucose showed a more balanced dependence on glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), greater reserve mitochondrial respiration capacity, and increased mitochondrial population relative to standard media. Our results show that neurons cultured in artificially high glucose-containing media preferentially use glycolysis, opposite to what is known for neurons in vivo as the primary pathway for ATP maintenance. Changes in gene and protein expression levels corroborate these changes in function and additionally suggest that high glucose culture media increases neuronal inflammation. We suggest using neuronal culture systems in 5 mM glucose to better represent physiologically relevant neuronal respiration.
    Keywords:  cell culture; glucose; mitochondrial respiration; neurobasal media; neuronal bioenergetics; primary mouse neuron
    DOI:  https://doi.org/10.1111/jnc.70125
  11. Cell Regen. 2025 Jun 16. 14(1): 25
    Mitochondrial deoxyguanosine kinase depletion induced ROS causes melanocyte stem cell exhaustion and hair greying.
    Kaiyao Zhou, Gangyun Wu, Rui Dong, Changhao Kan, Lin Xie, Lijuan Gao, Hua Li, Jianwei Sun, Wenxiu Ning.
      Hair pigmentation is regulated by melanocyte stem cells (MeSCs) within the hair follicle. Mitochondrial dysfunction is associated with hair depigmentation, primarily due to defects in melanogenesis. However, the mechanisms by which mitochondria support MeSCs during hair pigmentation remain obscure. In this study, we investigated the role of mitochondrial deoxyguanosine kinase (DGUOK), which provides guanosine and adenosine nucleotides for mitochondrial DNA (mtDNA) replication, in hair pigmentation and MeSCs maintenance. Dguok depleted and conditional knockout mice exhibit premature hair greying. This phenotype was not due to impaired melanin production by melanocytes but was associated with a significant loss of MeSCs and mature melanocytes. Notably, Dguok deficiency decreased the expression of 13 mtDNA-encoded genes, increased the levels of reactive oxygen species (ROS) and apoptosis in MeSCs. Treatment with N-acetylcysteine (NAC), an ROS inhibitor, effectively mitigated the depigmentation and rejuvenated the MeSCs population. These findings underscore the critical role of DGUOK in regulating mtDNA integrity, which is vital for sustaining MeSCs and ensuring hair pigmentation, providing valuable insights that may inform therapeutic strategies for combating hair greying.
    Keywords:  DGUOK; Hair pigmentation; MeSCs; Mitochondrial DNA; ROS
    DOI:  https://doi.org/10.1186/s13619-025-00242-0
  12. Diabetes Obes Metab. 2025 Jun 19.
    Type 2 diabetes and depression via microvascular dysfunction, neurodegeneration, inflammation, advanced glycation end products (AGEs), arterial stiffness.
    Indra L M Steens, Miranda T Schram, Alfons J H M Houben, Tos T J M Berendschot, Annemarie Koster, Hans Bosma, Simone J P M Eussen, Bastiaan E de Galan, Thomas T van Sloten.
       AIMS: Type 2 diabetes increases the risk of depression, but the mechanisms underlying this association are incompletely understood. We investigated whether microvascular dysfunction, neurodegeneration, low-grade inflammation, advanced glycation end products (AGEs) and arterial stiffness, pathologies that are more common in diabetes, explain, or mediate the association between type 2 diabetes and incident clinically relevant depressive symptoms.
    MATERIALS AND METHODS: We used prospective data from The Maastricht Study, a population-based cohort study. Diabetes status and potential mediators were assessed at baseline. Clinically relevant depressive symptoms (PHQ-9 score ≥10) were assessed at baseline and each year during a median of 8.1 (IQR 4.2, 10.1) years of follow-up. Mediation analysis was employed to investigate the mediating effect of microvascular dysfunction (retinal, blood and MRI biomarkers), neurodegeneration (retina and MRI biomarkers), low-grade inflammation (blood biomarkers), AGEs (skin and blood biomarkers) and arterial stiffness (tonometry and ultrasound biomarkers).
    RESULTS: Data of 6091 participants (age, 59.4 years [SD 8.6]; 51.3% women; 23.6% type 2 diabetes) were available. Type 2 diabetes was associated with a higher incidence of clinically relevant depressive symptoms (HR:1.37; 95% CI 1.13, 1.65). This association was partly mediated by microvascular dysfunction (proportion mediated:10.4% [95% CI:3.6%, 17.2%]); neurodegeneration (proportion mediated:12.1% [95% CI: 3.9%, 20.3%]); AGEs (proportion mediated:5.4% [95% CI: 3.0%, 8.8%]); and arterial stiffness (proportion mediated:8.4% [95% CI: 3.3%, 13.5%]); but not by low-grade inflammation.
    CONCLUSIONS: The association between type 2 diabetes and a higher risk of clinically relevant depressive symptoms is partly mediated by microvascular dysfunction, neurodegeneration, AGEs and arterial stiffness.
    Keywords:  cardiovascular disease; diabetes complications; population study; type 2 diabetes
    DOI:  https://doi.org/10.1111/dom.16527
  13. Cell Commun Signal. 2025 Jun 19. 23(1): 290
    Mitochondrial dysfunction in the regulation of aging and aging-related diseases.
    Xianhong Zhang, Yue Gao, Siyu Zhang, Yiqi Wang, Xinke Pei, Yufei Chen, Jinhui Zhang, Yichen Zhang, Yitian Du, Shauilin Hao, Yujiong Wang, Ting Ni.
      Aging is an irreversible physiological process that progresses with age, leading to structural disorders and dysfunctions of organs, thereby increasing the risk of chronic diseases such as neurodegenerative diseases, diabetes, hypertension, and cancer. Both organismal and cellular aging are accompanied by the accumulation of damaged organelles and macromolecules, which not only disrupt the metabolic homeostasis of the organism but also trigger the immune response required for physiological repair. Therefore, metabolic remodeling or chronic inflammation induced by damaged tissues, cells, or biomolecules is considered a critical biological factor in the organismal aging process. Notably, mitochondria are essential bioenergetic organelles that regulate both catabolism and anabolism and can respond to specific energy demands and growth repair needs. Additionally, mitochondrial components and metabolites can regulate cellular processes through damage-associated molecular patterns (DAMPs) and participate in inflammatory responses. Furthermore, the accumulation of prolonged, low-grade chronic inflammation can induce immune cell senescence and disrupt immune system function, thereby establishing a vicious cycle of mitochondrial dysfunction, inflammation, and senescence. In this review, we first outline the basic structure of mitochondria and their essential biological functions in cells. We then focus on the effects of mitochondrial metabolites, metabolic remodeling, chronic inflammation, and immune responsesthat are regulated by mitochondrial stress signaling in cellular senescence. Finally, we analyze the various inflammatory responses, metabolites, and the senescence-associated secretory phenotypes (SASP) mediated by mitochondrial dysfunction and their role in senescence-related diseases. Additionally, we analyze the crosstalk between mitochondrial dysfunction-mediated inflammation, metabolites, the SASP, and cellular senescence in age-related diseases. Finally, we propose potential strategies for targeting mitochondria to regulate metabolic remodeling or chronic inflammation through interventions such as dietary restriction or exercise, with the aim of delaying senescence. This reviewprovide a theoretical foundation for organismal antiaging strategies.
    Keywords:  Aging-related diseases; Cellular senescence; Chronic inflammation; Metabolic remodelling; Mitochondria
    DOI:  https://doi.org/10.1186/s12964-025-02308-7
  14. Front Pharmacol. 2025 ;16 1545356
    Improvement on mitochondrial energy metabolism of Codonopsis pilosula (Franch.) Nannf. polysaccharide.
    He Li, Letian Zhang, Xingtai Li, Haocheng He, Guoan Fu, Yi Zhun Zhu, Wei Hu, Lige Qiu, Liang Gong, Youming Zhang.
       Ethnopharmacological relevance: Codonopsis pilosula (Franch.) Nannf. (CP) is one of the most popular Qi-invigorating herbal medicines and has been extensively used to promote health and vitality in China for a long time. Codonopsis pilosula (Franch.) Nannf. polysaccharide (CPP) is the principal active components of CP, which is considered as the reason for CP widespread application. However, it has not been revealed that CPP exert a Qi-invigoration effect by protecting mitochondria and/or improving mitochondrial function in the existing traditional Chinese medicine theories.
    Aim of the study: We extracted CPP from C. pilosula and investigated the effects of CPP on energy metabolism and mitochondrial protection.
    Methods: Based on the mice chronic hypoxia model for imitating the energy deficiency state of the human body, which was administered with CPP by oral gavage daily for 10 days, mitochondrial permeability transition (MPT), lipid peroxidation product malondialdehyde (MDA) in brain, mitochondrial respiratory function, the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in liver cells were assayed. Adenylate energy charge (AEC), total adenylate pool (TAP), ATP/ADP, and ATP/AMP ratios were calculated.
    Results: CPP can inhibit the formation of MDA in mice brains, decrease oxygen consuming rate and respiratory control ratio (RCR) of liver mitochondria, increase levels of ATP, TAP and AEC in liver cells under chronic hypoxia condition.
    Conclusion: CPP can possess and improve mitochondrial energy metabolism and bioenergetic levels.
    Keywords:  Codonopsis pilosula (Franch.) Nannf. polysaccharide; adenosine triphosphate; anti-hypoxia; energy metabolism; mitochondria; mitochondrial respiratory function
    DOI:  https://doi.org/10.3389/fphar.2025.1545356
  15. Front Immunol. 2025 ;16 1579924
    Unveiling the role of NAD glycohydrolase CD38 in aging and age-related diseases: insights from bibliometric analysis and comprehensive review.
    Xianghui Zhao, Peiying Lv, Zixing Cai, Jun Dong, Wenxiang Chen, Liang Sun, Ruiyue Yang.
       Background: CD38, a glycoprotein with a single transmembrane structure, is extensively found in erythrocytes, immune cells, and endothelial cells. Primarily located on cell membranes, it plays a critical role in metabolizing nicotinamide adenine dinucleotide (NAD), thereby maintaining NAD homeostasis in vivo. As a vital coenzyme, NAD is involved in numerous biological processes, including energy metabolism, apoptosis, and DNA repair. CD38, as a major NAD-depleting enzyme, is pivotal in regulating intracellular NAD levels and various physiological processes. Given its significance, understanding the function of CD38 and its implications in aging and age-related diseases is crucial for elucidating disease pathogenesis and developing therapeutic strategies.
    Methods: This study conducted a bibliometric analysis to explore recent research trends and advancements in the field of CD38. Research articles were retrieved from the Web of Science database, followed by a bibliometric assessment using CiteSpace and VOSviewer to visualize key publication trends, contributions by countries and institutions, and keyword distributions. Based on the bibliometric analysis, key insights were synthesized to elucidate the role of CD38 in aging and age-related diseases, its underlying mechanisms, and its applications in clinical evaluation, detection methods, interventions, and therapeutic targets.
    Results: The bibliometric analysis revealed an exponential increase in the number of published articles over time, with the United States and China emerging as the leading research hubs. The predominant keywords included 'CD38' and 'blood-related disorders'. Furthermore, key findings highlighted the critical role of CD38 in aging and age-related diseases, emphasizing its mechanisms in NAD metabolism and its potential as a therapeutic target. Moreover, current applications of CD38 in clinical evaluation and detection methods were discussed, showcasing its growing importance in biomedical research.
    Conclusion: This study underscores the growing interest in CD38 research, particularly its role in aging and age-related diseases. The findings highlight the significance of CD38 in maintaining NAD homeostasis and its potential as a therapeutic target. The exponential growth in publications and the dominance of the United States and China in this field reflect the global importance of CD38 research. Future studies should further explore the mechanistic insights and clinical applications of CD38 to advance therapeutic strategies for age-related diseases.
    Keywords:  CD38; aging; bibliometric analysis; metabolic diseases; tumors
    DOI:  https://doi.org/10.3389/fimmu.2025.1579924
  16. Curr Drug Metab. 2025 Jun 16.
    Exploring the Effects of Oxidative Stress on Female Reproductive Function: The Role of Antioxidant Supplementation.
    Dala N Daraghmeh, Sawsan Salameh, Massa Zahdeh, Rania Ghanem, Rafik Karaman.
       BACKGROUND: The female reproductive system is susceptible to oxidative stress, which can interfere with ovulation, menstrual cycles, egg quality, and tubal function, ultimately leading to infertility. Antioxidants might play a crucial role in protecting reproductive health by neutralizing Reactive Oxygen Species (ROS) and preventing cellular damage.
    OBJECTIVE: To provide an overview of the research that has been performed on the benefits of antioxidant supplementation for increasing female fertility.
    METHODS: We conducted a comprehensive search of PubMed, Embase, and Google for full-text, English-lan-guage publications between 2000 and 2023 that investigated the relationship between antioxidant supplemen-tation and improvements in female fertility.
    RESULTS: Antioxidants have been investigated for their potential to improve fertility outcomes in subfertile women. Antioxidant supplementation shows promise in mitigating these effects by neutralizing excess ROS and restoring balance, leading to improved egg count and fertility outcomes. However, it is important to note that the effectiveness of antioxidant supplementation can vary depending on individual health factors and the specific antioxidants used. Studies suggest that a combination of antioxidants, such as vitamins C and E, se-lenium, and coenzyme Q10, may be more beneficial than single supplements. Although individual research has shown beneficial correlations between different antioxidant supplementation and female fertility, study repeatability is poor. As a result, further large-scale, well-designed clinical trials are necessary to better un-derstand the precise role and optimal combinations of antioxidants for enhancing fertility in subfertile women.
    CONCLUSION: This review study offers crucial insights into the complex connection between OS and female reproductive health. It highlights the potential advantages of antioxidant supplements as a preventative strat-egy. To enhance female fertility outcomes, further research, particularly randomized controlled clinical trials, is needed to determine best practices, identify populations that could benefit the most, and explore innovative antioxidant treatments.
    Keywords:  Antioxidants; female infertility; oxidative stress.; reactive oxygen species
    DOI:  https://doi.org/10.2174/0113892002357565250604075932
  17. Proc Natl Acad Sci U S A. 2025 Jun 24. 122(25): e2503677122
    Gut sulfide metabolism modulates behavior and brain bioenergetics.
    Roshan Kumar, Delawrence J Sykes, Victor I Band, Megan L Schaller, Romel Patel, Victor Vitvitsky, Peter Sajjakulnukit, Rashi Singhal, Harrison K A Wong, Suchitra K Hourigan, Fumito Ichinose, Costas A Lyssiotis, Yatrik M Shah, Ruma Banerjee.
      The host-microbiome interface is rich in metabolite exchanges and exquisitely sensitive to diet. Hydrogen sulfide (H2S) is present at high concentrations at this interface and is a product of both microbial and host metabolism. The mitochondrial enzyme, sulfide quinone oxidoreductase (SQOR), couples H2S detoxification to oxidative phosphorylation; its inherited deficiency presents as Leigh disease. Since an estimated two-thirds of systemic H2S metabolism originates in the gut, it raises questions as to whether impaired sulfide clearance in this compartment contributes to disease and whether it can be modulated by dietary sulfur content. In this study, we report that SQOR deficiency confined to murine intestinal epithelial cells perturbs colon bioenergetics that is reversed by antibiotics, revealing a significant local contribution of microbial H2S to host physiology. We also find that a 2.5-fold higher methionine intake, mimicking the difference between animal and plant proteins, synergizes with intestinal SQOR deficiency to adversely impact colon architecture and alter microbiome composition. In serum, increased thiosulfate, a biomarker of H2S oxidation, reveals that intestinal SQOR deficiency combined with higher dietary methionine affects sulfide metabolism globally and perturbs energy metabolism as indicated by higher ketone bodies. The mice exhibit lower exploratory locomotor activity while brain MRI reveals an atypical reduction in ventricular volume, which is associated with lower aquaporin 1 that is important for cerebrospinal fluid secretion. Our study reveals the dynamic interaction between dietary sulfur intake and sulfide metabolism at the host-microbe interface, impacting gut health, and the potential for lower dietary methionine intake to modulate pathology.
    Keywords:  gut–brain axis; hydrogen sulfide; ketone body; methionine; sulfide quinone oxidoreductase
    DOI:  https://doi.org/10.1073/pnas.2503677122
  18. Climacteric. 2025 Jun 18. 1-9
    Hormone therapy and insulin resistance in non-diabetic postmenopausal women: a systematic review and meta-analysis.
    Tanya Li, Nathan S Jiang, Julia Kaskey, Peter F Schnatz, Matthew Nudy.
       OBJECTIVE: Menopause increases the risk of insulin resistance and cardiometabolic diseases. This study summarizes the effects of hormone therapy (HT) on insulin resistance in non-diabetic postmenopausal women.
    METHOD: The study analyzed randomized controlled trials (1998-2024) that assessed the impact of HT on insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR) in non-diabetic postmenopausal women. Raw mean differences (RMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analysis compared estrogen alone (E alone) and estrogen plus progestogen (E + P) to placebo.
    RESULTS: Seventeen randomized controlled trials with 5772 women (3644 on HT: E alone [n = 1259] or E + P [n = 2385]; 2128 on placebo) were included. The weighted mean (standard deviation) age was 56.91 (5.95) years, with treatment lasting 8 weeks to 3 years. HT significantly reduced HOMA-IR (RMD = -0.24 [-0.32 to -0.16], p < 0.001, I2 = 60.3%). Subgroup analysis showed reductions in both E alone (RMD = -0.42 [-0.55 to -0.29], p < 0.001, I2 = 35%) and E + P (RMD= -0.14 [-0.23 to -0.04], p = 0.005, I2 = 13.7%) compared to placebo.
    CONCLUSION: HT significantly lowers insulin resistance in healthy, non-diabetic postmenopausal women, with E alone yielding greater reductions than combination therapy.
    Keywords:  Hormone therapy; cardiovascular disease risk factors; estrogen therapy; insulin resistance; postmenopausal women
    DOI:  https://doi.org/10.1080/13697137.2025.2509844
This page is being maintained by Thomas Krichel. It was last updated on 2025‒07‒24 at 17:45.