bims-mistre 2026-01-04 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2026–01–04
sixteen papers selected by
Ellen Siobhan Mitchell, MitoQ

A blood based mitochondrial functional index biomarker for Alzheimer's disease.
Mitochondrial bioenergetics dysfunction in T2DM: linking oxidative stress to insulin resistance.
Unraveling sex differences in age-related hippocampal decline: differential mitochondrial dysfunction, Lonp1-dependent mitochondrial proteostasis and mtROS production in aged C57BL/6 mice.
Reprogramming the Mitochondrion in Atherosclerosis: Targets for Vascular Protection.
Not Aging but Calorie Restriction Strongly Affects Protein Oxidation in Heart and Brain Mitochondria.
Type 3 Diabetes: A Molecular Link Between Cerebral Insulin Resistance and Neurodegeneration via AGE-RAGE Signaling.
SIRT3-Mediated Mitochondrial Regulation and Driver Tissues in Systemic Aging.
Clinical Strategies for Counteracting Human Ovarian Aging: Molecular Background, Update, and Outlook.
Mitoquinone mesylate enhances bovine oocyte in vitro maturation efficiency by modulating oxidative stress and enhancing mitochondrial function.
Antioxidant Natural Compounds Integrated with Targeted Protein Degradation: A Multi-Modal Strategy for Alzheimer's Disease Therapy.
Lifetime Deletion of Skeletal Muscle Keap1 Attenuates Aging-Induced Cardiac Dysfunction via an Nrf2-Antioxidant Mechanism.
Coenzyme Q10 supplementation increases blood concentrations but shows limited and inconsistent effects on exercise performance: A systematic review and meta-analysis.
β-Nicotinamide Mononucleotide Enhances Skin Barrier Function and Attenuates UV-B-Induced Photoaging in Mice.
Mitochondria and Lipids in Cellular Signaling of the Brain: from Physiology to Neurodegeneration.
Insulin levels early in perimenopause inform vasomotor symptom incidence across the menopausal transition.
Functional Impact Score of Mitochondrial Variants and Its Relationship With Functional Connectivity of the Brain: Potential Origins of Premature Aging in Young Adulthood.

Alzheimers Dement. 2025 Dec;21(12): e71061

A blood based mitochondrial functional index biomarker for Alzheimer's disease.

Brittany M Hauger, Riley E Kemna, Paul J Kueck, Taylor A Strope, Casey S John, Keith P Smith, Hana D Mayfield, Ellen Herrold, Keri L Cox, Rebecca Bothwell, Leonidas Bantis, Russell H Swerdlow, Jill K Morris, Heather M Wilkins.

   INTRODUCTION: Alzheimer's disease (AD) pathology is complex and involves mitochondrial dysfunction. There are emerging therapies targeting mitochondrial function in clinical trials for AD. This highlights the need for biomarkers that measure mitochondrial function.
METHODS: We determined the utility of a novel blood-based mitochondrial biomarker, the mitochondrial functional index (MFI), in the context of AD in a pilot study.
RESULTS: In vitro and in vivo models of AD had a reduced MFI. MFI was lower in human AD subjects and APOE 𝜀4 carriers. Receiver operating characteristic analysis showed MFI had a higher area under the curve than other plasma biomarkers. The MFI biomarker correlated with the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) scale.
DISCUSSION: This study highlights the potential utility of MFI as a functional blood-based mitochondrial biomarker to interrogate energy metabolism. Ongoing studies are examining the relationship of MFI with brain energy metabolism outcomes.
HIGHLIGHTS: The MFI biomarker is reduced in cell and animal models of AD. The MFI biomarker is reduced in human AD subjects and APOE ε4 carriers. The MFI biomarker can discriminate between subjects with normal cognition and AD with better performance than other plasma biomarkers. The MFI biomarker correlates with cognitive scores.

Keywords:  Alzheimer's disease; amyloid; biomarker; cognition; mitochondria; neurodegeneration; tau

DOI:  https://doi.org/10.1002/alz.71061
Front Endocrinol (Lausanne). 2025 ;16 1674477

Mitochondrial bioenergetics dysfunction in T2DM: linking oxidative stress to insulin resistance.

Zheng Feng, Zhenlin Tan, Donghui Lu.

  Insulin resistance (IR) is a core pathological feature of type 2 diabetes mellitus (T2DM) and is closely associated with mitochondrial dysfunction in insulin-sensitive tissues, including skeletal muscle, liver, and adipose tissue. Mitochondrial abnormalities-such as impaired oxidative phosphorylation (OXPHOS), dysregulated tricarboxylic acid (TCA) cycle, excessive reactive oxygen species (ROS) production, and altered mitochondrial dynamics-can contribute to IR by oxidatively modifying insulin-signaling proteins and activating inflammatory pathways (JNK/NF-κB). Recent work also implicates microRNAs (miRNAs) as modulators that link mitochondrial function and redox balance to insulin action; however, their magnitude and tissue specificity in human T2DM remain to be defined. Therapeutic strategies that target mitochondrial bioenergetics and redox homeostasis show promise, while miRNA-directed approaches are emerging. This review provides an explanatory synthesis aimed at distinguishing associations within the mitochondria-ROS-insulin resistance axis supported by solid evidence from findings influenced by specific contexts, and outlines translational opportunities and their associated delivery bottlenecks.

Keywords:  delivery; electron transport chain; insulin resistance; mitochondria; oxidative stress; reverse electron transport; tricarboxylic acid cycle; type 2 diabetes

DOI:  https://doi.org/10.3389/fendo.2025.1674477
Cell Death Dis. 2025 Dec 30.

Unraveling sex differences in age-related hippocampal decline: differential mitochondrial dysfunction, Lonp1-dependent mitochondrial proteostasis and mtROS production in aged C57BL/6 mice.

Karina A Cicali, Claudia Jara, Daniela Cortés-Díaz, Matías Lira, Ítalo Fuentes, Alejandra Catenaccio, Josefa Arnaíz, Micaela Ricca, Sebastián Valenzuela, Carolina A Oliva, Daniela S Rivera, Cheril Tapia-Rojas.

Aging is a progressive process characterized by cellular and molecular damage leading to mitochondrial dysfunction and cognitive decline. Mitochondrial dysfunction is a critical factor in memory impairment in aging and neurodegenerative diseases. While sex differences in aging have been observed across various species, the underlying cellular and molecular mechanisms remain poorly understood, mainly focused on mitochondrial proteostasis. This study examined hippocampal-dependent cognitive decline and mitochondrial dysfunction in aged male and female C57BL/6 J mice. Our results reveal sex-dependent differences in cognitive impairment, with aged males exhibiting more significant deficits in spatial and localization memory, while aged females show impairments in recognition memory. Additionally, aged males display increased oxidative stress and exacerbated mitochondrial superoxide production, leading to more severe bioenergetic deficiencies. Conversely, aged females exhibit heightened mitochondrial permeability transition pore (mPTP) activity, suggesting a distinct mechanism of mitochondrial dysfunction, which could explain, almost in part, the cognitive differences in aging. Investigating possible mechanisms responsible for this mitochondrial dysfunction, we found that mitochondrial proteostasis is more prone to failure in aged males, with a significant decrease in the protease activity of Lonp1, a key matrix mitochondrial protease degrading >50% of the mitochondrial proteome. To further reinforce these findings, we replicated key experiments in SAMP8 mice, a model of accelerated aging, obtaining consistent results that strengthen the robustness and generalization of our conclusions. These findings suggest that sex influences hippocampal aging at multiple levels, highlighting the need to consider sexual dimorphism in aging research. This study also emphasizes the critical role of mitochondrial proteostasis in maintaining mitochondrial function in aging in a sex-dependent manner. Understanding these differences could facilitate the development of sex-specific strategies to mitigate age-related cognitive decline and neurodegeneration.

DOI: https://doi.org/10.1038/s41419-025-08360-y
Antioxidants (Basel). 2025 Dec 05. pii: 1462. [Epub ahead of print]14(12):

Reprogramming the Mitochondrion in Atherosclerosis: Targets for Vascular Protection.

Patrycja Anna Glogowski, Federica Fogacci, Cristina Algieri, Antonia Cugliari, Fabiana Trombetti, Salvatore Nesci, Arrigo Francesco Giuseppe Cicero.

  Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, with a substantial proportion of events occurring prematurely. Atherosclerosis (AS), the central driver of cardiovascular pathology, results from the convergence of metabolic disturbances, vascular inflammation, and organelle dysfunction. Among intracellular organelles, mitochondria have emerged as critical regulators of vascular homeostasis. Beyond their canonical role in adenosine triphosphate (ATP) production, mitochondrial dysfunction-including impaired mitochondrial oxidative phosphorylation (OXPHOS), excessive generation of reactive oxygen species (ROS), accumulation of mitochondrial DNA (mtDNA) damage, dysregulated dynamics, and defective mitophagy-contributes to endothelial dysfunction, vascular smooth muscle cell (VSMC) phenotypic switching, macrophage polarization, and ultimately plaque initiation and destabilization. These insights have established the rationale for mitochondrial "reprogramming"-that is, the restoration of mitochondrial homeostasis through interventions enhancing biogenesis, dynamics, and quality control-as a novel therapeutic paradigm. Interventions that enhance mitochondrial biogenesis, restore mitophagy, and rebalance fission-fusion dynamics are showing promise in preclinical models of vascular injury. A growing array of translational strategies-including small-molecule activators such as resveratrol and Mitoquinone (MitoQ), gene-based therapies, and nanoparticle-mediated drug delivery systems-are under active investigation. This review synthesizes current mechanistic knowledge on mitochondrial dysfunction in ASand critically appraises therapeutic approaches aimed at vascular protection through mitochondrial reprogramming.

Keywords:  atherosclerosis (AS); endothelial dysfunction; mitochondrial reprogramming; mitophagy; nanoparticle-based therapies; vascular protection; vascular smooth muscle cells (VSMC)

DOI:  https://doi.org/10.3390/antiox14121462
Aging Cell. 2026 Jan;25(1): e70339

Not Aging but Calorie Restriction Strongly Affects Protein Oxidation in Heart and Brain Mitochondria.

Shipan Fan, Carina Ramallo-Guevara, Monika Frenzel, Shuichi Yanai, Sataro Goto, Michiru D Sugawa, Norbert A Dencher, Ansgar Poetsch.

  Aging is an inevitable consequence for all organisms. According to the mitochondrial free radical theory of aging (MFRTA), reactive oxygen species (ROS), which are predominantly generated in mitochondria, are assumed to play a key role. Calorie restriction (CR) delays aging by improving mitochondrial function; however, the molecular mechanisms underlying the effects of ROS and CR on mitochondria remain poorly understood. Oxidative protein modifications in mitochondrial proteins from the heart and cerebrum of young (6.5 months) and old (27 months) rats were quantified and the effects of short-term and lifelong CR interventions were investigated. Mass spectrometry was leveraged to achieve an unbiased and comprehensive analysis of various types of oxidative postranslational modifications (oxPTMs). Contrary to the MFRTA, aging did not cause significant increases in mitochondrial protein oxidation in the heart and cerebrum. CR markedly diminished the overall level of oxPTMs in the heart, particularly in transmembrane proteins. Similarly, the level of oxidative modification of transmembrane proteins in cerebrum was reduced by CR, whereas it perplexingly increased in mitochondrial proteins. The absolute level of oxidized mitochondrial protein was always higher in the heart than in the cerebrum under all conditions. Carbonylation, a prevalent marker of protein oxidation and aging, increased in the heart with age and was notably reduced by CR. However, this trend was not consistent in cerebrum or for some other types of oxPTMs. Therefore, protein oxidation in the heart and cerebrum exhibits distinct responses to chronological aging and dietary interventions, with the latter exerting a stronger influence.

Keywords:  aging; calorie restriction; mitochondria; oxidative modification

DOI:  https://doi.org/10.1111/acel.70339
Eur J Neurosci. 2026 Jan;63(1): e70364

Type 3 Diabetes: A Molecular Link Between Cerebral Insulin Resistance and Neurodegeneration via AGE-RAGE Signaling.

Ankit Verma, Manju Sharma, Ozair Alam, Tarique Anwer.

  Type 3 diabetes, a term that underscores the pathological connection between Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), emphasizes the role of cerebral insulin resistance and metabolic dysfunction in neuron degeneration. Cerebral insulin resistance impairs Akt signaling, leading to the suppression of GSK-3β activity, enhancement of tau hyperphosphorylation and neurofibrillary tangle formation. Concurrent impaired GLUT-3/4 translocation, mitochondrial function, and amyloid-β clearance exacerbate oxidative stress and plaque deposition. Collectively, these disruptions compromise synaptic plasticity and cognition, accelerating AD progression. Moreover, activation of AGE-RAGE-NF-κB signaling amplifies neuroinflammation, further aggravating tau and Aβ pathology. This interaction activates downstream MAPK, ERK1/2, and JNK/STAT pathways, which in turn stimulate transcription factors such as NF-κB, TGF-β, HIF-1α, and AP-1. The resulting cascade promotes oxidative stress, neuroinflammation, and PI3K/Akt/IRS-1 signaling impairment. Together, these interconnected pathways accelerate neuronal loss and cognitive decline. Emerging evidence indicates that natural bioactive compounds offer therapeutic benefits in AD by attenuating AGE-RAGE-mediated oxidative stress, neuroinflammation, and cerebral insulin resistance, thereby reducing amyloid-β accumulation and tau hyperphosphorylation. This review highlights the AGE-RAGE axis as a critical molecular mediator connecting T2DM and AD, orchestrating neuroinflammation, mitochondrial dysfunction, and tau hyperphosphorylation. Therapeutic strategies aimed at inhibiting AGE formation or blocking RAGE activation represent promising approaches to attenuate cognitive decline associated with Type 3 diabetes.

Keywords:  AGE–RAGE pathway; Alzheimer's disease; Type 3 diabetes; cerebral insulin resistance; cognitive decline; neuroinflammation

DOI:  https://doi.org/10.1111/ejn.70364
Genes (Basel). 2025 Dec 15. pii: 1497. [Epub ahead of print]16(12):

SIRT3-Mediated Mitochondrial Regulation and Driver Tissues in Systemic Aging.

Kate Šešelja, Ena Šimunić, Sandra Sobočanec, Iva I Podgorski, Marija Pinterić, Marijana Popović Hadžija, Tihomir Balog, Robert Belužić.

  Mitochondrial dysfunction is a defining hallmark of aging that connects redox imbalance, metabolic decline, and inflammatory signaling across organ systems. The mitochondrial deacetylase SIRT3 preserves oxidative metabolism and proteostasis, yet its age-related decline transforms metabolically demanding organs into sources of pro-senescent cues. This review synthesizes evidence showing how SIRT3 loss in select "driver tissues"-notably liver, adipose tissue, vascular endothelium, bone-marrow macrophages, and ovary-initiates systemic aging through the release of cytokines, oxidized metabolites, and extracellular vesicles. We discuss molecular routes and mediators of senescence propagation, including the senescence-associated secretory phenotype (SASP), mitochondrial-derived vesicles, and circulating mitochondrial DNA, as well as sex-specific modulation of SIRT3 by hormonal and intrinsic factors. By integrating multi-tissue and sex-dependent data, we outline a framework in which SIRT3 activity defines the mitochondrial threshold separating local adaptation from systemic aging spread. Targeting SIRT3 and its NAD+-dependent network may offer a unified strategy to restore mitochondrial quality, dampen chronic inflammation, and therefore recalibrate the aging dynamics of an organism.

Keywords:  NAD+ metabolism; SIRT3; aging drivers; extracellular vesicles; inflammaging; mitochondrial acetylation; senescence; sex differences; systemic aging

DOI:  https://doi.org/10.3390/genes16121497
Int J Mol Sci. 2025 Dec 12. pii: 11973. [Epub ahead of print]26(24):

Clinical Strategies for Counteracting Human Ovarian Aging: Molecular Background, Update, and Outlook.

Jan Tesarik, Raquel Mendoza Tesarik.

  Ovarian aging (OA) results from the senescence of different cell types present in the ovary, decreasing female fertility and quality of life and augmenting the risk of a variety of fertility-unrelated pathological conditions. The changes observed in the ovarian cells are accompanied by changes occurring in various elements of the hypothalamic-pituitary-ovarian (HPO) axis, the complex endocrine system that regulates the female reproductive cycle. Issues pertaining to the HPO axis have been addressed in animal models via hormonal treatments with preparations inhibiting ovarian follicular recruitment at the level of the receptors of gonadotropin-releasing hormone (GnRH)-secreting neurons, mainly acting on glutamate- and gamma-aminobutyric acid (GABA)-driven signaling. GnRH agonists and antagonists have also been used in women exposed to chemotherapeutics. HPO-independent OA can be delayed through the administration of different antioxidants and mitochondria-protecting agents, among which melatonin has been shown to be particularly useful. Other therapeutic approaches used with success in women include hormonal and growth factor (GF) modulators, such as growth hormone (GH), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factors (VEGF), and dehydroepiandrosterone (DHEA), and the development of patient-tailored combination-based therapies (IGF-1 + VEGF + DHEA) has also been suggested. Intraovarian injection of autologous platelet-rich plasma (PRP), mitochondrial donation through pronuclear transfer, and ovarian tissue cryopreservation and autotransplantation have also yielded promising results in women, and their use can preserve not only fertility but also the ovarian endocrine function. Personalized mixtures of specific agents (desatinib, quercetin, rapamycin, metformin, resveratrol, melatonin, and coenzyme Q10) targeting different cell types in the ovary are currently under investigation. Overall, this review aims to present a global view of the subject, uniting the physiological and molecular background of this pathology with the history and development of potential treatment strategies and new perspectives in this domain. As such, this study may be helpful both to clinicians facing problems resulting from OA and to researchers pursuing further developments in this field.

Keywords:  antioxidant and mitochondrial treatment; fertility preservation; hormonal and growth factor modulation; hypothalamic-pituitary-ovarian axis; ovarian aging; precision medicine

DOI:  https://doi.org/10.3390/ijms262411973
Theriogenology. 2025 Dec 29. pii: S0093-691X(25)00524-2. [Epub ahead of print]253 117798

Mitoquinone mesylate enhances bovine oocyte in vitro maturation efficiency by modulating oxidative stress and enhancing mitochondrial function.

Yongxin Li, Mengman Li, Hongtao Wang, Xiaoxin Chen, Hu Luan, Junwei Lv, Xintao Li, Jingchun Li, Lichun Zhang.

  This study probed the regulatory role of mitoquinone mesylate (MitoQ) on oxidative stress (OS) and mitochondrial function during the in vitro maturation (IVM) of bovine oocytes. To this end, MitoQ was added to the IVM medium at concentrations of 0, 50, 100, and 150 nmol/L. Compared with untreated controls, supplementation with 50 nmol/L MitoQ significantly improved the first polar body extrusion (PBE) rate, cleavage rate, and blastocyst formation rate (P < 0.05). Biochemical and cellular analyses further revealed that treatment with 50 nmol/L MitoQ led to a marked reduction in apoptotic death and intracellular reactive oxygen species (ROS) content (P < 0.01), accompanied by significant increases in glutathione (GSH) content and adenosine triphosphate (ATP) production (P < 0.05). In addition, mitochondrial membrane potential (MMP) was significantly elevated in the 50 nmol/L MitoQ group compared to controls (P < 0.01). Gene expression analysis indicated that antioxidant-related genes (SOD, SIRT2, SIRT3) and mitochondrial dynamics-associated genes (DNM1, DNM2, MFN2) were significantly upregulated (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001). Conversely, the pro-apoptotic gene BAX was significantly downregulated (∗∗P < 0.01), whereas expression of the anti-apoptotic gene BCL-2 was significantly increased (∗P < 0.05). Collectively, these findings demonstrate that supplementation of IVM medium with 50 nmol/L MitoQ effectively alleviates OS-induced injury, enhances mitochondrial energy metabolism, and substantially improves oocyte maturation quality and subsequent embryonic developmental potential.

Keywords:  Bovine oocytes; IVM; Mitochondrial function; Mitoquinone mesylate

DOI:  https://doi.org/10.1016/j.theriogenology.2025.117798
Antioxidants (Basel). 2025 Nov 27. pii: 1426. [Epub ahead of print]14(12):

Antioxidant Natural Compounds Integrated with Targeted Protein Degradation: A Multi-Modal Strategy for Alzheimer's Disease Therapy.

Desh Deepak Singh, Dharmendra Kumar Yadav, Dongyun Shin.

  Alzheimer's disease (AD) Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by protein aggregation, oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation, leading to cognitive decline. Current therapies remain largely symptomatic, highlighting the need for multi-target therapeutic strategies. Recent advances in antioxidant natural compounds and targeted protein degradation (TPD) technologies-particularly proteolysis-targeting chimeras (PROTACs), offer complementary mechanisms for disease modification. Natural antioxidants, including flavonoids, polyphenols, terpenoids, and alkaloids, confer neuroprotection by reducing reactive oxygen species, activating Nrf2 pathways, restoring mitochondrial function, and suppressing neuroinflammation. PROTACs, in contrast, selectively degrade pathological proteins such as hyperphosphorylated tau, amyloid-β, and APP fragments through the ubiquitin-proteasome system. The integrated "Antiox-PROTAC" approach combines these modalities to simultaneously mitigate oxidative stress and eliminate neurotoxic proteins. Natural compounds may act as warheads or scaffolds in PROTAC design, retaining antioxidant activity while enabling targeted degradation. Early preclinical findings demonstrate synergistic neuroprotective potential, though translational challenges remain, including blood-brain barrier permeability, bioavailability, and delivery optimization. Future directions involve hybrid molecules, nanoparticle-based delivery, and personalized therapeutic strategies. Overall, the Antiox-PROTAC paradigm represents a next-generation, multi-modal framework with the potential to modify disease progression and enhance cognitive outcomes in Alzheimer's disease.

Keywords:  Alzheimer’s disease; PROTACs; amyloid-β; antioxidant natural compounds; neuroprotection; oxidative stress; targeted protein degradation; tau protein

DOI:  https://doi.org/10.3390/antiox14121426
Antioxidants (Basel). 2025 Dec 12. pii: 1491. [Epub ahead of print]14(12):

Lifetime Deletion of Skeletal Muscle Keap1 Attenuates Aging-Induced Cardiac Dysfunction via an Nrf2-Antioxidant Mechanism.

Kanika Sharma, Sarah Pribil Pardun, Neha Dhyani, Irving H Zucker, Bipin G Nair, Sudarslal Sadasivan Nair, Vikas Kumar, Lie Gao.

  Background: Aging elevates reactive oxygen species (ROS) and weakens antioxidant defenses, contributing to cardiac dysfunction. The objective of this study was to determine whether sustained activation of skeletal muscle (SkM) Nrf2 preserves cardiac function during aging and to explore the underlying mechanisms, focusing on myocardial antioxidant pathways. Methods: Tamoxifen-induced SkM-specific Keap1 knockout male mice (iMS-Keap1flox/flox; SkM-Nrf2 overexpression) were divided into young wild-type (Y-WT), aged wild-type (A-WT), and aged knockout (A-KO) groups. Cardiac performance was evaluated by echocardiography and invasive hemodynamics. Myocardial proteomics identified differentially expressed proteins (DEPs) and enriched biological pathways. Results: Compared with Y-WT, A-WT mice showed impaired left ventricular function, including reduced ejection fraction, prolonged isovolumic relaxation time, blunted inotropic response to dobutamine, and elevated Tau index. These age-related deficits were partially reversed in A-KO mice. Proteomic analysis revealed 561 DEPs between A-WT and Y-WT, and 741 DEPs between A-KO and A-WT, enriched in calcium signaling, Nrf2-mediated oxidative stress response, oxidative phosphorylation, ROS detoxification, and cardiac-specific processes, such as hypertrophy, conduction, and dilated cardiomyopathy. Conclusions: Lifelong SkM-Nrf2 activation strengthens myocardial antioxidant capacity and alleviates age-related cardiac dysfunction. These data support an antioxidant crosstalk between skeletal muscle and the heart, highlighting a potential therapeutic target for aging-associated heart failure.

Keywords:  Keap1 knockout; aging; cardiac dysfunction; interorgan antioxidant crosstalk; myocardial proteomics; nuclear factor erythroid 2-related factor

DOI:  https://doi.org/10.3390/antiox14121491
Br J Nutr. 2025 Dec 29. 1-56

Coenzyme Q10 supplementation increases blood concentrations but shows limited and inconsistent effects on exercise performance: A systematic review and meta-analysis.

Hengzhi Deng, Tianyu Song, Mingyue Yin, Kai Xu, Yuming Zhong, Norsyazmi Bin Mohd, Mohamed Nashrudin Bin Naharudin, Ashril Yusof, Xiaohan Fan.

  Coenzyme Q10 (CoQ10) is biologically plausible as an ergogenic aid through roles in mitochondrial energy production and antioxidant defence, yet findings from randomised trials are inconsistent. This review included 24 studies from 6 databases published up to November 2025, assessing effects of CoQ10 on exercise performance, subjective fatigue, and circulating CoQ10 levels in healthy adults. Randomised trials comparing CoQ10 with placebo were synthesised using a three-level model. Risk of bias was assessed with RoB2 and certainty judged with GRADE.Supplementation consistently increased blood CoQ10, indicating robust biochemical responsiveness. In contrast, performance effects were small and inconsistent. In primary analyses, chronic supplementation showed a small benefit, whereas acute supplementation showed no benefit. After excluding outliers, the chronic effect was no longer stable and the acute effect remained trivial. All subgroup analyses were restricted to chronic supplementation. Within this context, aerobic endurance was significant in primary analyses but became borderline after outlier exclusion, while anaerobic and strength outcomes showed little change. Evidence for reduced subjective fatigue was suggestive and became more consistent after outlier exclusion. Benefits in trained individuals were unstable and became consistent only after outlier exclusion. No stable dose-response pattern emerged for supplementation dosage or duration. Heterogeneity and moderate-to-high risk of bias reduced certainty.Collectively, CoQ10 reliably elevates circulating levels but provides at most modest and context-dependent benefits for exercise performance, largely under chronic use. Overall certainty is very low to low. Well-controlled randomised trials that standardise formulation, dose, and duration and examine sex-specific and endurance-related responses are needed.

Keywords:  Antioxidant supplementation; Blood CoQ10; Coenzyme Q10; Exercise performance; Meta-analysis

DOI:  https://doi.org/10.1017/S0007114525106211
Antioxidants (Basel). 2025 Nov 27. pii: 1424. [Epub ahead of print]14(12):

β-Nicotinamide Mononucleotide Enhances Skin Barrier Function and Attenuates UV-B-Induced Photoaging in Mice.

Sung Jin Kim, Sullim Lee, Yea Jung Choi, Minseo Kang, Junghwan Lee, Gwi Seo Hwang, Seok-Seon Roh, Mu Hyun Jin, Sangki Park, Minji Park, Ho Song Cho, Ki Sung Kang.

  Ultraviolet B (UV-B) radiation significantly contributes to skin photoaging, which is characterized by epidermal thickening, collagen degradation, wrinkle formation, barrier dysfunction, and oxidative stress. Nicotinamide mononucleotide (NMN), a key precursor of nicotinamide adenine dinucleotide, regulates cellular energy metabolism and antioxidant defense and demonstrates anti-aging effects in animal models. Here, we investigated the protective effects of oral NMN supplementation against UV-B-induced photoaging in SKH-1 hairless mice. Over a 10-week experimental period, oral NMN administration significantly alleviated epidermal hypertrophy, reduced wrinkle formation and skin surface roughness, improved hydration and elasticity, and restored transepidermal water loss to near-normal levels. Histological analyses revealed marked preservation of collagen fiber density and attenuation of dermal matrix degradation. Furthermore, NMN supplementation inhibited the phosphorylation of MAPK signaling components (ERK, JNK, and p38), suppressed pro-inflammatory cytokine (TNF-α and IL-6) and matrix-degrading enzyme (MMP-1) expression, and restored hyaluronan synthase (HAS-1 and HAS-2) expression. Additionally, NMN enhanced the systemic antioxidant defense, as indicated by the restored superoxide dismutase activity. Thus, NMN has multi-layered protective effects against UV-B-induced skin aging by modulating oxidative stress, inflammatory signaling, extracellular matrix remodeling, and hyaluronic acid metabolism.

Keywords:  UV-B–induced photoaging; extracellular matrix remodeling; nicotinamide mononucleotide (NMN); oxidative stress; skin barrier function

DOI:  https://doi.org/10.3390/antiox14121424
Mol Cell Biol. 2026 Jan 02. 1-19

Mitochondria and Lipids in Cellular Signaling of the Brain: from Physiology to Neurodegeneration.

Plamena R Angelova, Lauren Millichap, Andrey Y Abramov.

  The brain is one of the most lipid-rich organs, reflecting the critical role of lipid metabolism in neuronal and glial cell function. While mitochondria are central to energy metabolism, calcium signaling, and cell death, they do not utilize lipid oxidation for energy but rely on lipids for membrane integrity and intracellular communication. Here we review the interactions between lipids and mitochondria in intracellular signaling within brain cells, examining their roles in normal physiology and the mechanisms underlying major neurodegenerative diseases. Alterations in lipid homeostasis and mitochondrial metabolism are implicated in neurodegeneration, highlighting the importance of lipid-mediated mitochondrial signaling pathways. Understanding these interactions provides insights into cellular dysfunction in neurodegenerative disorders and may inform future therapeutic strategies targeting lipid and mitochondrial pathways.

Keywords:  Lipid signaling; calcium signaling; lipid peroxidation; mitochondria; neurodegeneration

DOI:  https://doi.org/10.1080/10985549.2025.2607428
J Clin Endocrinol Metab. 2026 Jan 03. pii: dgaf699. [Epub ahead of print]

Insulin levels early in perimenopause inform vasomotor symptom incidence across the menopausal transition.

Faria Athar, Sarah Gregory, Emma J Houston, Nicole M Templeman.

   CONTEXT: Metabolic health impacts the menopausal transition. Metabolic characteristics like body mass index (BMI) affect vasomotor syndrome incidence, but the role of elevated insulin, an early marker of metabolic dysfunction, remains understudied.
OBJECTIVE: To determine whether midlife insulin levels are associated with vasomotor symptom incidence or reproductive hormone trajectories.
METHODS: Longitudinal analyses of community-based data from the Study of Women's Health Across the Nation (SWAN) were conducted. We analyzed the 704 SWAN participants (of 3302) without oophorectomy or hysterectomy who had metabolic data for age 47 and did not take insulin/medications for hyperglycemia. Mean fasting insulin at 47 was 10.117 µIU/mL (SD = 6.711), with 27.0 kg/m2 BMI (SD = 6.6); mean age of final menstrual period for these participants was 51.0 years (SD = 2.3). Main outcome measures included vasomotor symptom timings and durations, and trajectories of estradiol, follicle-stimulating hormone (FSH), and testosterone across the menopausal transition.
RESULTS: Higher insulin at 47 predicted younger onsets of hot flashes and night sweats, longer durations of hot flashes and cold sweats, and greater testosterone rise. BMI associations with vasomotor symptoms paralleled those of insulin, but BMI appeared more closely linked to slower estradiol decline and blunted FSH rise. In Cox proportional hazards models, elevated age-47 insulin was associated with increased likelihood of hot flashes; this remained significant with BMI and glucose as covariates.
CONCLUSIONS: Perimenopausal fasting insulin and BMI show complementary but distinct associations with menopausal changes. Elevated insulin predicts earlier and prolonged vasomotor symptoms, and is associated with higher testosterone.

Keywords:  Study of Women's Health Across the Nation (SWAN); androgen; climacteric; hot flashes; hyperinsulinemia; insulin resistance

DOI:  https://doi.org/10.1210/clinem/dgaf699
Hum Brain Mapp. 2026 Jan;47(1): e70447

Functional Impact Score of Mitochondrial Variants and Its Relationship With Functional Connectivity of the Brain: Potential Origins of Premature Aging in Young Adulthood.

Klara Mareckova, Ana Paula Mendes-Silva, Radek Mareček, Tomáš Jordánek, Anna Pačínková, Jana Klánová, Vanessa F Gonçalves, Yuliya S Nikolova.

  Alterations in mitochondrial DNA (mtDNA) have been associated with worse cognitive abilities in older adults and premature epigenetic aging in young adulthood. However, it is not clear how mitochondrial dysfunction affects brain function in young adulthood and whether cognition-related networks might be most affected. We tested whether mtDNA functional impact (FI) score might map onto specific patterns of between-network functional connectivity in young adults from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC). We also tested whether these relationships might be mediated by accelerated epigenetic aging, calculated using Horvath's epigenetic clock, CheekAge clock, and AltumAge clock. General connectivity method was used as a reliable marker of individual differences in brain function. We showed that a greater mtDNA FI score was associated with lower connectivity between the dorsal attention and language networks (beta = -0.41, p = 0.0007, AdjR2 = 0.15) and that there was suggestive evidence that this relationship might be mediated by accelerated epigenetic aging calculated using Horvath's epigenetic clock in young adulthood (ab = -0.061, SE = 0.04, 95% CI [-0.163; 0.001], 90% CI [-0.142; -0.002]). These findings were independent of sex, current BMI, and current substance use. Overall, we conclude that individuals with a greater mtDNA FI score might be at greater risk of experiencing worse attention to relevant linguistic inputs, greater difficulties with speech comprehension, and verbal working memory.

Keywords:  dorsal attention network; functional impact score of mitochondrial variants (mtDNA FI score); general connectivity; language network; mitochondria dysfunction; young adulthood

DOI:  https://doi.org/10.1002/hbm.70447