bims-mistre 2025-04-20 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–04–20
seventeen papers selected by
Ellen Siobhan Mitchell, MitoQ

The cell origin of reactive oxygen species and its implication for evolutionary trade-offs.
Current study on Pyrroloquinoline quinone (PQQ) therapeutic role in neurodegenerative diseases.
Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities.
Active control of mitochondrial network morphology by metabolism-driven redox state.
Relationship between Alzheimer's Disease and Type 2 Diabetes: Critical Review On Cellular and Molecular Common Pathogenic Mechanisms.
The Role of Aromatic Amino Acids in Polycystic Ovary Syndrome through Patients' Blood Metabolic Profiling: A Systematic Review of the Past Five Years.
The Dual Role of Oxidative Stress in Atherosclerosis and Coronary Artery Disease: Pathological Mechanisms and Diagnostic Potential.
Oxidative Stress in Brain Function.
VDAC1-Targeted NHK1 Peptide Recovers Mitochondrial Dysfunction Counteracting Amyloid-β Oligomers Toxicity in Alzheimer's Disease.
Mechanisms Linking Obesity, Insulin Resistance, and Alzheimer's Disease: Effects of Polyphenols and Omega-3 Polyunsaturated Fatty Acids.
Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases.
Premature aging and metabolic diseases: the impact of telomere attrition.
Evaluation of Metabolic Dysfunction-Associated Fatty Liver Disease-Related Pathogenic Mechanisms in Human Steatotic Liver Cell-Based Model: Beneficial Effects of Prunus domestica L. subsp. syriaca Extract.
Sirtuins and Resveratrol in Cardiorenal Diseases: A Narrative Review of Mechanisms and Therapeutic Potential.
Chlorogenic Acid Improves High-Fat Diet-Induced Skeletal Muscle Metabolic Disorders by Regulating Mitochondrial Function and Lactate Metabolism.
The Janus Face of Oxidative Stress and Hydrogen Sulfide: Insights into Neurodegenerative Disease Pathogenesis.
Understanding the connection between stress and sleep: From underlying mechanisms to therapeutic solutions.

Open Biol. 2025 Apr;15(4): 240312

The cell origin of reactive oxygen species and its implication for evolutionary trade-offs.

Maïly Kervella, Fabrice Bertile, Frédéric Bouillaud, François Criscuolo.

  The allocation of resources in animals is shaped by adaptive trade-offs aimed at maximizing fitness. At the heart of these trade-offs, lies metabolism and the conversion of food resources into energy, a process mostly occurring in mitochondria. Yet, the conversion of nutrients to utilizable energy molecules (adenosine triphosphate) inevitably leads to the by-production of reactive oxygen species (ROS) that may cause damage to important biomolecules such as proteins or lipids. The 'ROS theory of ageing' has thus proposed that the relationship between lifespan and metabolic rate may be mediated by ROS production. However, the relationship is not as straightforward as it may seem: not only are mitochondrial ROS crucial for various cellular functions, but mitochondria are also actually equipped with antioxidant systems, and many extra-mitochondrial sources also produce ROS. In this review, we discuss how viewing the mitochondrion as a regulator of cellular oxidative homeostasis, not merely a ROS producer, may provide new insights into the role of oxidative stress in the reproduction-survival trade-off. We suggest several avenues to test how mitochondrial oxidative buffering capacity might complement current bioenergetic and evolutionary studies.

Keywords:  ageing theory; bioenergetics; longevity; oxidative metabolism; oxidative stress

DOI:  https://doi.org/10.1098/rsob.240312
Mol Biol Rep. 2025 Apr 15. 52(1): 397

Current study on Pyrroloquinoline quinone (PQQ) therapeutic role in neurodegenerative diseases.

Tao Xie, Zhen Zhang, Mingzhe Feng, Lingbo Kong.

  Pyrroloquinoline quinone (PQQ) is a naturally occurring redox-active compound with potent antioxidant, mitochondrial-enhancing, and neuroprotective properties. Originally identified as a cofactor in bacterial enzymes, PQQ has garnered significant interest for its potential therapeutic role in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). It has reported that PQQ exerts its effects through several key molecular mechanisms, including the activation of antioxidant pathways via Nrf2/ARE signaling, enhancement of mitochondrial biogenesis and function through AMPK/PGC-1α, and the regulation of inflammatory processes through NF-κB inhibition. By improving cellular energy metabolism, reducing oxidative stress, and promoting neuronal survival, PQQ offers a multifaceted approach to counteracting the pathophysiological factors underlying neurodegeneration. Our review focusing on current study of PQQ on its enhancing neuroplasticity, and protecting neurons from damage induced by oxidative stress, mitochondrial dysfunction, and inflammation. Further we reviewed the significant signaling pathways that involved PQQ neuroprotective mechanisms, positioning it as a novel candidate for future therapeutic strategies targeting these debilitating conditions.

Keywords:  Alzheimer’s disease (AD); Neurodegenerative diseases; Parkinson’s disease (PD); Pyrroloquinoline quinone (PQQ); ROS; Signaling pathways

DOI:  https://doi.org/10.1007/s11033-025-10491-6
Stem Cell Res Ther. 2025 Apr 15. 16(1): 180

Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities.

Yun Liao, Stacia Octaviani, Zhen Tian, Samuel R Wang, Chunlan Huang, Jian Huang.

  Mitochondrial quality control (MQC) is a critical mechanism for maintaining mitochondrial function and cellular metabolic homeostasis, playing an essential role in the self-renewal, differentiation, and long-term stability of hematopoietic stem cells (HSCs). Recent research highlights the central importance of MQC in HSC biology, particularly the roles of mitophagy, mitochondrial biogenesis, fission, fusion and mitochondrial transfer in regulating HSC function. Mitophagy ensures the removal of damaged mitochondria, maintaining low levels of reactive oxygen species (ROS) in HSCs, thereby preventing premature aging and functional decline. Concurrently, mitochondrial biogenesis adjusts key metabolic regulators such as mitochondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) to meet environmental demands, ensuring the metabolic needs of HSCs are met. Additionally, mitochondrial transfer, as an essential form of intercellular material exchange, facilitates the transfer of functional mitochondria from bone marrow stromal cells to HSCs, contributing to damage repair and metabolic support. Although existing studies have revealed the significance of MQC in maintaining HSC function, the precise molecular mechanisms and interactions among different regulatory pathways remain to be fully elucidated. Furthermore, the potential role of MQC dysfunction in hematopoietic disorders, including its involvement in disease progression and therapeutic resistance, is not yet fully understood. This review discusses the molecular mechanisms of MQC in HSCs, its functions under physiological and pathological conditions, and its potential therapeutic applications. By summarizing the current progress in this field, we aim to provide insights for further research and the development of innovative treatment strategies.

Keywords:  Hematopoietic stem cell; Mitochondrial biogenesis; Mitochondrial dynamics; Mitochondrial metabolism; Mitochondrial quality control; Mitochondrial transfer; Mitophagy

DOI:  https://doi.org/10.1186/s13287-025-04304-7
Proc Natl Acad Sci U S A. 2025 Apr 22. 122(16): e2421953122

Active control of mitochondrial network morphology by metabolism-driven redox state.

Gaurav Singh, Vineeth Vengayil, Aayushee Khanna, Swagata Adhikary, Sunil Laxman.

  Mitochondria are dynamic organelles that constantly change morphology. What controls mitochondrial morphology however remains unresolved. Using actively respiring yeast cells growing in distinct carbon sources, we find that mitochondrial morphology and activity are unrelated. Cells can exhibit fragmented or networked mitochondrial morphology in different nutrient environments independent of mitochondrial activity. Instead, mitochondrial morphology is controlled by the intracellular redox state, which itself depends on the nature of electron entry into the electron transport chain (ETC)-through complex I/II or directly to coenzyme Q/cytochrome c. In metabolic conditions where direct electron entry is high, reactive oxygen species (ROS) increase, resulting in an oxidized cytosolic environment and rapid mitochondrial fragmentation. Decreasing direct electron entry into the ETC by genetic or chemical means, or reducing the cytosolic environment rapidly restores networked morphologies. Using controlled disruptions of electron flow to alter ROS and redox state, we demonstrate minute-scale, reversible control between networked and fragmented forms in an activity-independent manner. Mechanistically, the fission machinery through Dnm1 responds in minute-scale to redox state changes, preceding the change in mitochondrial form. Thus, the metabolic state of the cell and its consequent cellular redox state actively control mitochondrial form.

Keywords:  electron transport chain; mitochondrial network; reactive oxygen species; redox state

DOI:  https://doi.org/10.1073/pnas.2421953122
Curr Alzheimer Res. 2025 Apr 11.

Relationship between Alzheimer's Disease and Type 2 Diabetes: Critical Review On Cellular and Molecular Common Pathogenic Mechanisms.

Arantxa Rodríguez-Casado, Mª Isabel Álvarez, José-Joaquín Merino, Adolfo Toledano-Díaz, Adolfo Toledano.

   OBJECTIVE/BACKGROUND: Type 2 Diabetes Mellitus (T2D) and Alzheimer's disease (AD) are two diseases with a high prevalence today that share common pathophysiological mechanisms, suggesting a potential causal relationship between them. AD is also known as Type 3 Diabetes Mellitus (T3D). A complete understanding of this complex issue (T2D-AD) is necessary to develop fully effective and easily applicable therapies that do not yet exist. A critical update on the subject is presented, delving into the pathophysiological implications and defining new research for promoting new therapeutic interventions.
METHODS: Revision and critical analysis of the described and observed cellular and molecular common pathogenic T2D-AD mechanisms in human and model studies.
RESULTS: Both diseases exhibit common genetic, epigenetic, biochemical and physiological characteristics. Pathogenic mechanisms such as peripheral inflammation, mitochondrial dysfunction, oxidative stress, insulin resistance, hyperglycemia, formation of advanced glycation end products, neuroinflammation, neuroglial dysfunctions, and deposition of aberrant misfolded proteins are commonly displayed in dysmetabolic diseases and AD. The T2D, AD and T2D-AD pathogenic courses present several close key contacts (or identities). The clinical course of T2D has different incidences in the neurodegenerative course of AD (from its onset to its aggravation). There are theoretical, practical and interpretative problems in studies on human and experimental models, as well as in the clinical and pathological interpretation of T2D-AD dementia, which are of great importance in the development of knowledge of this subject and the therapeutic application of its results.
CONCLUSION: In recent years, there has been a great advance in the study of the relationships between T2D (and related dysmetabolic diseases) and AD. There is no doubt about their close relationship and/or the inclusion of AD as a metabolic disease (T3D). Joint therapies seem to be absolutely necessary. Key pathogenic processes (insulin resistance, genetic and epigenetic regulation, peripheral inflammation and neuroinflammation) must be investigated to develop new and effective therapies.

Keywords:  Alzheimer's disease (AD); Type 3 diabetes (T3D); epigenetic causes.; genetic causes; hyperglycemia; insulin resistance; mitochondrial dysfunction; neuroglial dysfunction; neuroinflammation; neuronal degeneration; oxidative stress; pathogenic mechanisms; peripheral inflammation; type 2 diabetes (T2D)

DOI:  https://doi.org/10.2174/0115672050375461250325074826
J Proteome Res. 2025 Apr 17.

The Role of Aromatic Amino Acids in Polycystic Ovary Syndrome through Patients' Blood Metabolic Profiling: A Systematic Review of the Past Five Years.

Apostolos Gkantzos, Stavros Kalogiannis, Olga Deda.

  Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of reproductive age that encompasses a multitude of signs and symptoms, including hyperandrogenism, polycystic ovarian morphology, ovulatory dysfunction, and insulin resistance. The study aims to explore the role of aromatic amino acid (AAA) disorders in the syndrome. A systematic search on the databases Scopus, PubMed, and Google Scholar until 20 July 2024 over the past 5 years regarding metabolomic studies on PCOS patients' blood and the status of AAAs resulted in 12 related papers. Our review showed that AAA metabolic pathways are dysregulated, and their levels in the blood serum and plasma of PCOS patients in most studies are elevated due to inflammation and oxidative stress which, assisted by gut dysbiosis, give rise to insulin resistance that develops into PCOS. AAA abnormalities can also directly induce the defining symptoms of the syndrome through diminished neurotransmitter availability and impaired signaling. According to our review, AAA perturbations are detected in every stage of PCOS pathophysiology, making them valuable biomarkers for early diagnosis and management of the syndrome. Further investigation of the biological function, role, and impact of AAAs, probably alongside other metabolites, including BCAAs, could lead to the discovery of new tools for preventing and managing PCOS symptoms.

Keywords:  Aromatic Amino Acids; Inflammation; Insulin Resistance; Metabolomics; Phenylalanine; Polycystic Ovary Syndrome; Tryptophan; Tyrosine

DOI:  https://doi.org/10.1021/acs.jproteome.4c00937
Antioxidants (Basel). 2025 Feb 26. pii: 275. [Epub ahead of print]14(3):

The Dual Role of Oxidative Stress in Atherosclerosis and Coronary Artery Disease: Pathological Mechanisms and Diagnostic Potential.

Marcin Myszko, Jerzy Bychowski, Elżbieta Skrzydlewska, Wojciech Łuczaj.

  Oxidative stress plays a pivotal role in the pathogenesis of atherosclerosis and coronary artery disease (CAD), with both beneficial and detrimental effects on cardiovascular health. On one hand, the excessive production of reactive oxygen species (ROS) contributes to endothelial dysfunction, inflammation, and vascular remodeling, which are central to the development and progression of CAD. These pathological effects drive key processes such as atherosclerosis, plaque formation, and thrombosis. On the other hand, moderate levels of oxidative stress can have beneficial effects on cardiovascular health. These include regulating vascular tone by promoting blood vessel dilation, supporting endothelial function through nitric oxide production, and enhancing the immune response to prevent infections. Additionally, oxidative stress can stimulate cellular adaptation to stress, promote cell survival, and encourage angiogenesis, which helps form new blood vessels to improve blood flow. Oxidative stress also holds promise as a source of biomarkers that could aid in the diagnosis, prognosis, and monitoring of CAD. Specific oxidative markers, such as malondialdehyde (MDA), isoprostanes (isoP), ischemia-modified albumin, and antioxidant enzyme activity, have been identified as potential indicators of disease severity and therapeutic response. This review explores the dual nature of oxidative stress in atherosclerosis and CAD, examining its mechanisms in disease pathogenesis as well as its emerging role in clinical diagnostics and targeted therapies. The future directions for research aimed at harnessing the diagnostic and therapeutic potential of oxidative stress biomarkers are also discussed. Understanding the balance between the detrimental and beneficial effects of oxidative stress could lead to innovative approaches in the prevention and management of CAD.

Keywords:  acute coronary syndrome; antioxidants; atherosclerosis; oxidative stress; reactive oxygen species

DOI:  https://doi.org/10.3390/antiox14030275
Antioxidants (Basel). 2025 Feb 28. pii: 297. [Epub ahead of print]14(3):

Oxidative Stress in Brain Function.

Daniela-Marilena Trofin, Dragos-Petrica Sardaru, Dan Trofin, Ilie Onu, Andrei Tutu, Ana Onu, Cristiana Onită, Anca Irina Galaction, Daniela Viorelia Matei.

  Oxidative stress (OS) is an important factor in the pathophysiology of numerous neurodegenerative disorders, such as Parkinson's disease, multiple sclerosis, cerebrovascular pathology or Alzheimer's disease. OS also significantly influences progression among the various neurodegenerative disorders. The imbalance between the formation of reactive oxygen species (ROS) and the body's capacity to neutralize these toxic byproducts renders the brain susceptible to oxidative injury. Increased amounts of ROS can result in cellular malfunction, apoptosis and neurodegeneration. They also represent a substantial factor in mitochondrial dysfunction, a defining characteristic of neurodegenerative disorders. Comprehending the fundamental mechanisms of OS and its interactions with mitochondrial function, neuroinflammation and cellular protective pathways becomes essential for formulating targeted therapeutics to maintain brain health and reduce the impacts of neurodegeneration. We address recent highlights on the role of OS in brain function in terms of significance for neuronal health and the progression of neurodegenerative disorders.

Keywords:  Alzheimer disease; Parkinson disease; brain function; multiple sclerosis; oxidative stress; physical exercise; stroke

DOI:  https://doi.org/10.3390/antiox14030297
Aging Cell. 2025 Apr 13. e70069

VDAC1-Targeted NHK1 Peptide Recovers Mitochondrial Dysfunction Counteracting Amyloid-β Oligomers Toxicity in Alzheimer's Disease.

Fabrizio Cavallaro, Stefano Conti Nibali, Salvatore Antonio Maria Cubisino, Pietro Caruso, Stefania Zimbone, Iolanda Rita Infantino, Simona Reina, Vito De Pinto, Angela Messina, Maria Laura Giuffrida, Andrea Magrì.

  Mitochondrial dysfunction has been implicated in a broad range of age-related pathologies and has been proposed as a causative factor in Alzheimer's disease (AD). Analysis of post-mortem brains from AD patients showed increased levels of Voltage-dependent anion-selective channel 1 (VDAC1) in the dystrophic neurites surrounding amyloid-β (Aβ) deposits, suggesting a direct association between VDAC1 and mitochondrial toxicity. VDAC1 is the most abundant pore-forming protein of the outer mitochondrial membrane and, as a channel, it plays a pivotal role in regulating cellular bioenergetics, allowing the continuous exchange of ions and metabolites (ATP/ADP, Krebs cycle intermediates) between cytosol and mitochondria. In light of this evidence, we looked into the effects of Aβ oligomers on VDAC1 functions through electrophysiological and respirometric techniques. Our findings indicate that Aβ oligomers significantly modify the conductance, voltage dependency, and kinetic features of VDAC1, as well as its slight selectivity for anions, leading to a marked preference for cations. Given that VDAC1 is mainly involved in the trafficking of charged molecules in and out of mitochondria, a general reduction of cell viability and mitochondrial respiration was detected in neuroblastoma cells and primary cortical neurons exposed to Aβ oligomers. Interestingly, the toxic effect mediated by Aβ oligomers was counteracted by the use of NHK1, a small synthetic, cell-penetrating peptide that binds and modulates VDAC1. On these results, VDAC1 emerges as a crucial molecule in mitochondrial dysfunction in AD and as a promising pharmacological target for the development of new therapeutic avenues for this devastating neurodegenerative disease still without a cure.

Keywords:  Alzheimer's disease; VDAC1; amyloid‐β; interfering peptide; mitochondria

DOI:  https://doi.org/10.1111/acel.70069
Nutrients. 2025 Mar 29. pii: 1203. [Epub ahead of print]17(7):

Mechanisms Linking Obesity, Insulin Resistance, and Alzheimer's Disease: Effects of Polyphenols and Omega-3 Polyunsaturated Fatty Acids.

Mahsa Yavari, Nishan Sudheera Kalupahana, Breanna N Harris, Latha Ramalingam, Yujiao Zu, Chanaka Nadeeshan Kahathuduwa, Naima Moustaid-Moussa.

  Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and behavioral changes. It poses a significant global health challenge. AD is associated with the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain, along with chronic inflammation, dysfunctional neurons, and synapse loss. While the prevalence of AD continues to rise, the current FDA-approved drugs offer only limited effectiveness. Emerging evidence suggests that obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM) are also implicated in AD pathogenesis, with epidemiological studies and animal models confirming the impact of IR on Aβ accumulation, and high-fat diets also exacerbating Aβ accumulation. Since neuroinflammation activated by Aβ involves the nuclear factor kappa-light-chain-enhancer of the activated B cell (NF-κB) pathway, the inhibition of NF-κB and NLRP3 inflammasome activation are potential therapeutic strategies in AD. Bioactive compounds, including polyphenols (resveratrol, epigallocatechin-3-gallate, curcumin, and quercetin), and omega-3 polyunsaturated fatty acids, show promising results in animal studies and clinical trials for reducing Aβ levels, improving cognition and modulating the signaling pathways implicated in AD. This review explores the interplay between obesity, IR, inflammation, and AD pathology, emphasizing the potential of dietary compounds and their role in reducing inflammation, oxidative stress, and cognitive decline, as viable strategies for AD prevention and treatment. By integrating epidemiological findings, observational studies, and clinical trials, this review aims to provide a comprehensive understating of how metabolic dysfunctions and bioactive compounds influence AD progression.

Keywords:  Alzheimer’s disease; diabetes; insulin resistance; obesity; omega-3 polyunsaturated fatty acids; polyphenols

DOI:  https://doi.org/10.3390/nu17071203
Antioxidants (Basel). 2025 Feb 23. pii: 256. [Epub ahead of print]14(3):

Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases.

Claudia Penna, Pasquale Pagliaro.

  Endothelial dysfunction (ED) is characterized by an imbalance between vasodilatory and vasoconstrictive factors, leading to impaired vascular tone, thrombosis, and inflammation. These processes are critical in the development of cardiovascular diseases (CVDs) such as atherosclerosis, hypertension and ischemia/reperfusion injury (IRI). Reduced nitric oxide (NO) production and increased oxidative stress are key contributors to ED. Aging further exacerbates ED through mitochondrial dysfunction and increased oxidative/nitrosative stress, heightening CVD risk. Antioxidant systems like superoxide-dismutase (SOD), glutathione-peroxidase (GPx), and thioredoxin/thioredoxin-reductase (Trx/TXNRD) pathways protect against oxidative stress. However, their reduced activity promotes ED, atherosclerosis, and vulnerability to IRI. Metabolic syndrome, comprising insulin resistance, obesity, and hypertension, is often accompanied by ED. Specifically, hyperglycemia worsens endothelial damage by promoting oxidative stress and inflammation. Obesity leads to chronic inflammation and changes in perivascular adipose tissue, while hypertension is associated with an increase in oxidative stress. The NLRP3 inflammasome plays a significant role in ED, being triggered by factors such as reactive oxygen and nitrogen species, ischemia, and high glucose, which contribute to inflammation, endothelial injury, and exacerbation of IRI. Treatments, such as N-acetyl-L-cysteine, SGLT2 or NLRP3 inhibitors, show promise in improving endothelial function. Yet the complexity of ED suggests that multi-targeted therapies addressing oxidative stress, inflammation, and metabolic disturbances are essential for managing CVDs associated with metabolic syndrome.

Keywords:  NLRP3 inflammasome; antioxidant treatments; ischemia/reperfusion injury; metabolic syndrome; nitric oxide; oxidative stress

DOI:  https://doi.org/10.3390/antiox14030256
Front Aging. 2025 ;6 1541127

Premature aging and metabolic diseases: the impact of telomere attrition.

Sandhya Jinesh, Burçin Özüpek, Prerana Aditi.

  Driven by genetic and environmental factors, aging is a physiological process responsible for age-related degenerative changes in the body, cognitive decline, and impaired overall wellbeing. Notably, premature aging as well as the emergence of progeroid syndromes have posed concerns regarding chronic health conditions and comorbidities in the aging population. Accelerated telomere attrition is also implicated in metabolic dysfunction and the development of metabolic disorders. Impaired metabolic homeostasis arises secondary to age-related increases in the synthesis of free radicals, decreased oxidative capacity, impaired antioxidant defense, and disrupted energy metabolism. In particular, several cellular and molecular mechanisms of aging have been identified to decipher the influence of premature aging on metabolic diseases. These include defective DNA repair, telomere attrition, epigenetic alterations, and dysregulation of nutrient-sensing pathways. The role of telomere attrition premature aging in the pathogenesis of metabolic diseases has been largely attributed to pro-inflammatory states that promote telomere shortening, genetic mutations in the telomerase reverse transcriptase, epigenetic alteration, oxidative stress, and mitochondrial dysfunctions. Nonetheless, the therapeutic interventions focus on restoring the length of telomeres and may include treatment approaches to restore telomerase enzyme activity, promote alternative lengthening of telomeres, counter oxidative stress, and decrease the concentration of pro-inflammatory cytokines. Given the significance and robust potential of delaying telomere attrition in age-related metabolic diseases, this review aimed to explore the molecular and cellular mechanisms of aging underlying premature telomere attrition and metabolic diseases, assimilating evidence from both human and animal studies.

Keywords:  aging; metabolic diseases; premature aging; telomerase; telomere

DOI:  https://doi.org/10.3389/fragi.2025.1541127
Nutrients. 2025 Apr 03. pii: 1249. [Epub ahead of print]17(7):

Evaluation of Metabolic Dysfunction-Associated Fatty Liver Disease-Related Pathogenic Mechanisms in Human Steatotic Liver Cell-Based Model: Beneficial Effects of Prunus domestica L. subsp. syriaca Extract.

Laura Comi, Claudia Giglione, Fationa Tolaj Klinaku, Lorenzo Da Dalt, Hammad Ullah, Maria Daglia, Paolo Magni.

  Background/Objectives: Disrupted glucose uptake, oxidative stress, and increased de novo lipogenesis are some of the key features of metabolic dysfunction-associated fatty liver disease (MASLD). The modulation of these pathogenic mechanisms using extracts from natural and sustainable sources is a promising strategy to mitigate disease progression. This study aimed to evaluate the effects of Prunus domestica L. subsp. syriaca extract on these processes, taking advantage of a cell-based model of steatotic hepatocytes (HepG2-OA) that recapitulates some key pathophysiological features of MASLD. Methods: The HepG2-OA cell model was generated by treating cells for 7 days with 100 μM oleic acid (OA). The effect of different concentrations (0.01, 0.1, 0.5, and 1 mg/mL) of P. domestica extract was assessed through MTT assay (cell viability), flow cytometry (glucose uptake and reactive oxygen species, ROS, production), spectrophotometry (lipid accumulation), and qRT-PCR (expression of selected genes). Results: P. domestica extract exhibited no cytotoxicity at any tested concentration after 24 and 48 h in the HepG2-OA cells. The extract increased glucose uptake in a dose-dependent fashion after both 6 and 24 h. Additionally, the extract reduced lipid accumulation and downregulated the expression of key lipogenic genes (DGAT1 and FASN). Furthermore, in the HepG2-OA cells, P. domestica extract reduced ROS production and downregulated the expression of oxidative stress-related genes (SOD and CAT). Conclusions: P. domestica extract positively modulated some key molecular mechanisms associated with glucose metabolism, lipogenesis, and oxidative stress, supporting its potential as a nutraceutical candidate for MASLD management.

Keywords:  HepG2 hepatocytes; Prunus domestica L. subsp. syriaca; agro-food waste; glucose uptake; lipid accumulation; metabolic dysfunction-associated fatty liver disease (MASLD); natural extract; oleic acid; oxidative stress

DOI:  https://doi.org/10.3390/nu17071249
Nutrients. 2025 Mar 30. pii: 1212. [Epub ahead of print]17(7):

Sirtuins and Resveratrol in Cardiorenal Diseases: A Narrative Review of Mechanisms and Therapeutic Potential.

Caterina Carollo, Alessandra Sorce, Emanuele Cirafici, Giuseppe Mulè, Gregorio Caimi.

  Aging is a very complex process, and it has been linked with Sirtuins. Sirtuin enzymes are a family of deacetylases that are related to caloric restriction and aging by modulating energy metabolism, genomic stability, and stress resistance. Up to now, seven sirtuins have been recognized. This narrative review aimed to analyze the literature produced between January 2005 and March 2025 to evaluate the role of sirtuins in chronic kidney disease and, as heart and kidney diseases are strictly interrelated, to explore their role in heart diseases and cardio-renal cross-talk. A reciprocal relationship between CKD and aging seems to exist since CKD may contribute to premature biological aging of different organ systems. SIRTs are involved in the pathophysiology of renal diseases; their activation can delay the progression of several renal diseases. Notably, an increasing number of studies linked SIRTs with different CVDs. SIRTs affect the production of mitochondrial reactive oxygen species (ROS) by modulating mitochondrial function. The imbalance of SIRT levels may increase the vulnerability to CVDs. SIRTs are involved in the pathophysiological mechanisms of HFpEF (heart failure with preserved ejection fraction) through different signaling pathways. Fibrosis is the linkage mechanism between the heart and kidney in the development of cardio-renal diseases. Current studies on sirtuins, resveratrol, and cardiorenal disease highlight their potential therapeutic benefits in regulating blood pressure, kidney function, lipid profiles, and inflammation, making them a promising area of investigation for improving cardiovascular and renal health outcomes. However, significant gaps remain. The limited availability of highly selective and potent sirtuin modulators hampers their clinical translation, as most existing compounds exhibit poor bioavailability and suboptimal pharmacokinetic properties.

Keywords:  CKD; CRS; CVD; SIRTs; aging; cardiorenal syndromes; resveratrol; sirtuins

DOI:  https://doi.org/10.3390/nu17071212
J Agric Food Chem. 2025 Apr 15.

Chlorogenic Acid Improves High-Fat Diet-Induced Skeletal Muscle Metabolic Disorders by Regulating Mitochondrial Function and Lactate Metabolism.

Yu Wang, Juan Sun, Lamei Xue, Yujie Sun, Kuiliang Zhang, Mingcong Fan, Haifeng Qian, Yan Li, Li Wang.

  Mitochondria are pivotal in sustaining skeletal muscle and the systemic metabolic balance. Chlorogenic acid (CA) is a common dietary antioxidant known for its ability to modulate metabolic homeostasis. This study aimed to investigate the impact of CA on high-fat diet (HFD)-induced mitochondrial dysfunction and metabolic disorder in skeletal muscle. C57BL/6J mice fed with a HFD were treated with CA for 12 weeks. The study assessed the overall glycolipid metabolic status, exercise performance, muscle fiber type, and antioxidant capacity of skeletal muscle in HFD-fed mice treated with CA. Results showed that CA reduced fat accumulation, improved exercise capacity, and enhanced mitochondrial performance in HFD-fed mice. Untargeted metabolomics analysis revealed that lactate metabolism and mitochondrial fatty acid oxidation (FAO) responded positively to CA intervention. Molecular mechanisms demonstrated that CA intervention improved mitochondrial biogenesis and function, promoting FAO and oxidative phosphorylation in mitochondria and ultimately reducing fat deposition in skeletal muscle induced by HFD feeding. Mechanistically, CA decreased HFD-induced lactate production and protein lactylation in skeletal muscle, highlighting the importance of the LDHA-lactate axis in mitochondrial function improvement by CA. Therefore, this study provides additional insights supporting the potential of CA as a natural dietary supplement for metabolic syndrome and associated disorders.

Keywords:  LDHA; chlorogenic acid; lactate; mitochondrial function; skeletal muscle

DOI:  https://doi.org/10.1021/acs.jafc.5c03967
Antioxidants (Basel). 2025 Mar 19. pii: 360. [Epub ahead of print]14(3):

The Janus Face of Oxidative Stress and Hydrogen Sulfide: Insights into Neurodegenerative Disease Pathogenesis.

Constantin Munteanu, Anca Irina Galaction, Gelu Onose, Marius Turnea, Mariana Rotariu.

  Oxidative stress plays an essential role in neurodegenerative pathophysiology, acting as both a critical signaling mediator and a driver of neuronal damage. Hydrogen sulfide (H2S), a versatile gasotransmitter, exhibits a similarly "Janus-faced" nature, acting as a potent antioxidant and cytoprotective molecule at physiological concentrations, but becoming detrimental when dysregulated. This review explores the dual roles of oxidative stress and H2S in normal cellular physiology and pathophysiology, focusing on neurodegenerative disease progression. We highlight potential therapeutic opportunities for targeting redox and sulfur-based signaling systems in neurodegenerative diseases by elucidating the intricate balance between these opposing forces.

Keywords:  Janus face; hydrogen sulfide (H2S); neurodegenerative diseases; neuroinflammation; oxidative stress; redox signaling

DOI:  https://doi.org/10.3390/antiox14030360
Prog Brain Res. 2025 ;pii: S0079-6123(25)00016-0. [Epub ahead of print]291 137-159

Understanding the connection between stress and sleep: From underlying mechanisms to therapeutic solutions.

Matthew-Zane L Broderick, Qadir Khan, Nasrollah Moradikor.

  The objective of this chapter is to navigate through the nexus between stress and sleep, highlighting the neurobiological systems that connect them. Starting with an overview of neuroanatomy and physiology of stress and sleep, with a further detailed breakdown of sleep stages and key neuroanatomical centers that are responsible for sleep and wakefulness. Starting with suprachiasmatic nuclei (SCN) in circadian rhythm and sleep regulation overview, with a center point on the molecular systems including the CLOCK/CRY and BMAL1/2/PER1/2 feedback loops. Following this is the neurobiological of stress, specifically the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal (SPA) axis and influence on sleep. Vital neural circuits connecting stress and sleep are examined with the attention of the ventral tegmental area (VTA) GABA-somatostatin neurons and the locus coerules in sleep regulation in response to stress. In addition, neuroinflammation's role occurs through the cytokines IL-1β and TNF-α are investigated as a mediator of sleep disturbances caused by stress. It concludes by summarizing the implications of neuroinflammatory modulation in stress-related psychopathologies, emphasizing the opening this provides for interventions that target this inflammation helping to lighten sleep disorder.

Keywords:  Corticotropin-releasing hormone; Hypothalamic-pituitary-adrenal axis; Post-traumatic stress disorder; Retinohypothalamic tract; Sleep; Ventral tegmental area

DOI:  https://doi.org/10.1016/bs.pbr.2025.01.016