bims-mistre 2025-12-21 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2025–12–21
eleven papers selected by
Ellen Siobhan Mitchell, MitoQ

Revisiting ROS: duality in organ aging progression.
Comparison of anti-aging effect of PQQ (Pyrroloquinoline Quinone) and NMN/NR (Nicotinamide Mononucleotide /Nicotinamide Riboside) - possible combination use.
Neuroprotective Effect of Marine-Derived Nacre Extract against Aβ-Induced Toxicity via Preservation of Mitochondrial Function and Biogenesis.
Ergothioneine and exercise: A match made in (cognitive) heaven?
Association of DNA methylation-predicted growth differentiation factor 15 with all-cause mortality among older adults in the United States: A prospective cohort study of NHANES 1999 to 2002.
Pathogen-induced mitochondrial dysfunction: mechanistic insights, immune crosstalk, and therapeutic opportunities.
Kynurenic acid signaling expands in human and nonhuman primates and impairs dorsolateral prefrontal cortical cognition that is key to mental illness.
Integrative effects of saffron and physical activity on endurance performance, quality of life, cognitive, emotional, and metabolic outcomes in age-related and neurodegenerative diseases.
Gestational Diabetes Mellitus and Accelerated Biological Aging in Middle-Aged and Elderly Women.
Association of female reproductive traits with altered aging trajectories: Insights from genetic and observational analyses.
The mechanisms in glucose metabolism of aging hippocampus.

Mol Biol Rep. 2025 Dec 15. 53(1): 202

Revisiting ROS: duality in organ aging progression.

Mohan Yu, Shiyi Liu, Chenxin Zhang, Wen Yang.

  The functions of multiple organs decline with the process of aging. Revealing the intrinsic mechanisms governing organ degeneration is a critical pursuit for understanding the aging process and creating interventions for aging-related diseases. Macromolecular damage caused by the generation of reactive oxygen species (ROS) increases with the process of aging. However, excessive ROS generation may only partially account for aging at the individual and organ levels. In contrast, they could serve as important signaling molecules in stress responses. In this review, we focused on the dual role of ROS in the aging processes of several human organ systems. Through this investigation, we aim to reassess the relationship between ROS and aging.

Keywords:  Aging intervention; Aging-related diseases; Organ aging; Reactive oxygen species (ROS)

DOI:  https://doi.org/10.1007/s11033-025-11342-0
Ageing Res Rev. 2025 Dec 11. pii: S1568-1637(25)00338-1. [Epub ahead of print] 102992

Comparison of anti-aging effect of PQQ (Pyrroloquinoline Quinone) and NMN/NR (Nicotinamide Mononucleotide /Nicotinamide Riboside) - possible combination use.

Savani Ulpathakumbura, Sicong Kenric Lu, Rasika Gunarathne, John Zhiyong Yang, Johnson Liu, Xiaodong Jin, Qiang Zhou, Jun Lu.

  Aging is a complex biological process characterized by the gradual deterioration of cellular functions, leading to an increased susceptibility to chronic diseases. In the search for interventions to promote healthy aging and extend lifespan, Pyrroloquinoline Quinone (PQQ) and Nicotinamide Mononucleotide/Nicotinamide Riboside (NMN/NR) have emerged as promising anti-aging agents. PQQ exerts its anti-aging effect primarily through enhancing mitochondrial biogenesis, exerting antioxidant activity, and modulating inflammatory pathways. On the other hand, NMN/NR act as key precursors in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme involved in energy metabolism, cellular homeostasis, and DNA repair, thereby promoting longevity. This review systematically compares the mechanisms of action and efficacy of those compounds in mitigating age-related complications. Furthermore, this emphasizes the potent synergistic effect when PQQ and NMN/NR are used in combined formulations, highlighting their complementary pathways to support healthy aging. Despite supporting preliminary data and patented formulations, strong scientific evidence encouraging the synergistic anti-aging potential of PQQ and NMN/NR remains limited, highlighting the need for robust studies. Collectively, PQQ and NMN/NR offer distinct complementary strategies to promote healthy aging and prevent age-related diseases; their combination could offer a more effective approach to enhance healthy aging and longevity.

Keywords:  NMN; NR; PQQ; anti-aging

DOI:  https://doi.org/10.1016/j.arr.2025.102992
Neurochem Res. 2025 Dec 20. 51(1): 19

Neuroprotective Effect of Marine-Derived Nacre Extract against Aβ-Induced Toxicity via Preservation of Mitochondrial Function and Biogenesis.

Zhao Yan, Yamato Yotsuya, Yasushi Hasegawa.

  Pearls, formed from the nacreous layers of marine mollusks, have long been used in traditional medicine, yet the molecular basis of their bioactivity remains insufficiently characterized. Mitochondrial dysfunction is a central feature of Alzheimer's disease (AD) pathology and represents a critical therapeutic target. Although nacre extract has been reported to improve cognitive impairment, its effects on mitochondrial function and biogenesis under amyloid-β (Aβ)-induced toxicity remain unclear. In this study, we examined the impact of nacre extract on mitochondrial activity in PC12 cells and in an Aβ-injected mouse model. Treatment with nacre extract significantly alleviated Aβ-induced mitochondrial dysfunction in PC12 cells, restoring membrane potential, ATP production, and the expression of mitochondrial biogenesis-related genes, including PPARγ and Nrf1. MitoBright LT staining demonstrated recovery of mitochondrial mass following extract administration. In vivo, we first isolated and identified a sulfated polysaccharide fraction from nacre extract, which significantly improved Aβ-induced memory impairment. In parallel, this fraction preserved mitochondrial function in the brains of Aβ-injected mice, as evidenced by maintained membrane potential, ATP levels, and hippocampal succinate dehydrogenase expression. Together, these findings demonstrate that nacre extract exerts neuroprotective effects through its sulfated polysaccharide fraction, highlighting its potential as a marine-derived therapeutic resource against AD-related neurodegeneration.

Keywords:  Alzheimer's disease; Amyloid-β damage; Mitochondrial dysfunction; Nacre extract; PC12 cells

DOI:  https://doi.org/10.1007/s11064-025-04624-3
Ageing Res Rev. 2025 Dec 11. pii: S1568-1637(25)00339-3. [Epub ahead of print] 102993

Ergothioneine and exercise: A match made in (cognitive) heaven?

Vanessa Kristina Wazny, Jozo Grgic, Pedro L Valenzuela, Lei Feng, Andrea B Maier.

  Cognitive decline is one of the key challenges with aging, with significant implications for independence, quality of life, and healthcare burden. As pharmacological treatments remain limited in efficacy and often carry adverse effects, there is growing interest in safe, accessible, non-pharmacological strategies to preserve cognitive function. This Short Review explores the potential of combining two approaches that, individually, have shown beneficial effects on cognitive function: ergothioneine, a naturally occurring amino acid with antioxidant and anti-inflammatory properties, and physical exercise. Ergothioneine accumulates in the brain and other high-stress organs, where it modulates the redox balance, dampens chronic inflammation and supports mitochondrial function. Meanwhile, physical exercise has well-documented benefits for neuroplasticity, cerebral perfusion, and cognitive performance. Preclinical studies suggest ergothioneine supports exercise performance and muscle recovery without attenuating adaptive responses. Despite their distinct and complementary mechanisms, currently there are no available studies exploring the combined effects of ergothioneine and exercise on cognition. We propose a future research agenda that includes mechanistic animal studies, dose-response trials, and clinical interventions in at-risk populations. Together, the combination of ergothioneine and exercise may offer a low-risk, multifaceted approach to enhancing cognitive resilience in aging.

Keywords:  Aerobic Exercise; Antioxidants; Cognition; Cognitive Aging; Mitochondria/metabolism; Neurodegeneration; Neuroprotection; Oxidative Stress; Resistance Training

DOI:  https://doi.org/10.1016/j.arr.2025.102993
Medicine (Baltimore). 2025 Dec 12. 104(50): e46578

Association of DNA methylation-predicted growth differentiation factor 15 with all-cause mortality among older adults in the United States: A prospective cohort study of NHANES 1999 to 2002.

Meisheng Zou, Daofan Li, Suhong Wu.

  Growth differentiation factor 15 (GDF15) serves as a prominent biomarker across multiple physiological and pathological processes. Increased levels of GDF15 are associated with elevated mortality risk. Nevertheless, the prognostic utility of DNA methylation (DNAm)-predicted GDF15 concentrations for mortality remains inadequately explored. Our study utilized a national cohort to examine the link between GDF15 levels predicted by DNAm and the risk of all-cause mortality. This study employed data from the National Health and Nutrition Examination Survey (NHANES) cycles spanning 1999 to 2002. A regression model was applied to derive DNA methylation (DNAm)-predicted GDF15 concentrations. To evaluate the association linking DNA methylation-predicted GDF15 levels to mortality, we conducted adjusted Cox proportional hazards regression modeling. Dose-response relationships were evaluated using restricted cubic splines (RCS), and subgroup analyses were carried out to strengthen the findings' robustness. Elevated levels of GDF15 predicted via DNA methylation exhibited a marked association with increased all-cause mortality risk (HR = 1.11, 95% CI = 1.05-1.18). Participants within the top tertile of epigenetically estimated GDF15 concentrations exhibited a considerably increased hazard of death (HR = 1.62, 95% CI = 1.27-2.08). Kaplan-Meier curves demonstrated gradually decreasing survival probabilities corresponding to higher epigenetically derived GDF15 levels. A nonlinear dose-response relationship between DNAm-inferred GDF15 concentrations and all-cause mortality was revealed by restricted cubic spline analysis. This positive relationship consistently maintained significance within every prespecified subgroup. Epigenetically estimated GDF15 levels represent an independent predictor of all-cause mortality. This association retains its significance in multiple analytical approaches and across various subpopulations, highlighting the potential of GDF15 as a biomarker for stratifying mortality risk. Future studies are needed to elucidate the biological mechanisms through which GDF15 operates and to evaluate its applicability in clinical settings for reducing mortality risk.

Keywords:  DNA methylation; GDF15; NHANES; all-cause mortality; older adults

DOI:  https://doi.org/10.1097/MD.0000000000046578
Front Cell Infect Microbiol. 2025 ;15 1714998

Pathogen-induced mitochondrial dysfunction: mechanistic insights, immune crosstalk, and therapeutic opportunities.

Yang Yang, Yuanyuan Zeng, Zeyi Liu, Jian-An Huang.

  Mitochondria have emerged as multifunctional organelles central to cellular metabolism, innate immunity, and cell fate determination. Increasing evidence demonstrates that pathogens-including viruses, bacteria, fungi, and parasites-target mitochondria to modulate host immune responses and metabolic reprogramming. Disruption of mitochondrial dynamics, excessive reactive oxygen species (ROS) generation, mitochondrial DNA (mtDNA) release, and altered mitophagy represent key hallmarks of pathogen-induced mitochondrial dysfunction. These processes not only compromise cellular bioenergetics but also influence immune signaling cascades, such as cGAS-STING and NLRP3 inflammasome pathways, thereby shaping infection outcomes. This review synthesizes the latest findings on how distinct pathogen classes orchestrate mitochondrial damage and explores their implications for infection biology and immune regulation. Furthermore, we highlight emerging mitochondria-targeted therapeutic strategies and future research directions aimed at mitigating infection-induced mitochondrial pathology.

Keywords:  host defense; infection; mitochondria; mitochondrial dynamics; pathogens

DOI:  https://doi.org/10.3389/fcimb.2025.1714998
Mol Psychiatry. 2025 Dec 18.

Kynurenic acid signaling expands in human and nonhuman primates and impairs dorsolateral prefrontal cortical cognition that is key to mental illness.

Shengtao Yang, Dibyadeep Datta, Fenna M Krienen, Elizabeth Woo, Athena May, George M Anderson, Veronica C Galvin, Guillermo Gonzalez-Burgos, David A Lewis, Emi Ling, Steven A McCarroll, Amy Ft Arnsten, Min Wang.

Cognitive deficits from dorsolateral prefrontal cortex (dlPFC) dysfunction are common in neuroinflammatory disorders, including long-COVID, schizophrenia and Alzheimer's disease, where impairments are correlated with kynurenine inflammatory signaling. Kynurenine synthesis from tryptophan is increased under conditions of inflammation, then further metabolized to kynurenic acid (KYNA) in brain, where it blocks NMDA and α7-nicotinic receptors (nic-α7Rs). These receptors are essential for neurotransmission in dlPFC, suggesting that KYNA may contribute to higher cognitive deficits in these disorders. The current study employed several methods to examine the expression of KYNA and its synthetic enzyme, KAT II, in primate dlPFC, and to determine its effects on working memory-related dlPFC neuronal firing and cognitive functioning in aging macaques with naturally-occurring neuroinflammation. We found that KYNA, its synthetic enzyme, KAT II, and the gene encoding KAT II (AADAT), have greatly expanded expression in macaque and human dlPFC in both glia and neurons, with AADAT especially prominent in primate neurons compared to rodent PFC. In macaques, like humans, plasma kynurenine/tryptophan ratios increased with age, consistent with age-related increasing inflammation. Local application of KYNA onto dlPFC neurons markedly reduced the delay-related firing needed for working memory via actions at NMDA and nic-α7Rs, while inhibition of KAT II enhanced neuronal firing in aged macaques. Systemic administration of agents that reduce KYNA production similarly improved cognitive performance in aged monkeys. These data show that KYNA inflammatory signaling expands in primate dlPFC, and that inhibition of kynurenine-KYNA production may provide a powerful therapeutic avenue for treating higher cognitive deficits in neuroinflammatory disorders.

DOI: https://doi.org/10.1038/s41380-025-03425-y
Front Nutr. 2025 ;12 1698135

Integrative effects of saffron and physical activity on endurance performance, quality of life, cognitive, emotional, and metabolic outcomes in age-related and neurodegenerative diseases.

Lingyun Li, Kehai Wang.

  Age-related diseases, including cardiovascular disorders, type 2 diabetes, neurodegenerative conditions such as Alzheimer's and Parkinson's disease, and age-related eye diseases, represent leading causes of disability and mortality worldwide. Growing evidence highlights the therapeutic promise of non-pharmacological interventions, notably saffron (Crocus sativus L.) and structured exercise, both of which exert pleiotropic effects through antioxidant, anti-inflammatory, and neuroprotective pathways. In this review, we summarize current experimental and clinical data on saffron's bioactive compounds, crocin, crocetin, and safranal, and their capacity to modulate lipid metabolism, insulin sensitivity, mitochondrial function, and protein aggregation. Parallel findings from exercise research demonstrate improvements in cardiovascular function, glycemic control, neuroplasticity, and ocular health. Importantly, emerging studies reveal synergistic benefits when saffron supplementation is combined with physical activity, resulting in amplified improvements in vascular remodeling, glycemic regulation, neurotrophic signaling, and behavioral outcomes. These complementary interventions target shared molecular pathways, including PI3K/Akt/mTOR signaling, SIRT1-PGC-1α activation, Nrf2-mediated antioxidant defense, and modulation of inflammatory cytokines. Taken together, saffron and exercise represent safe, accessible, and multi-target strategies that may delay or attenuate the progression of aging-related diseases. Future large-scale, long-term clinical trials are warranted to establish optimal protocols and to integrate these interventions into preventive and therapeutic frameworks for healthy aging.

Keywords:  Alzheimer's disease; Parkinson's disease; aging; exercise; saffron

DOI:  https://doi.org/10.3389/fnut.2025.1698135
Diabetes Care. 2025 Dec 16. pii: dc251842. [Epub ahead of print]

Gestational Diabetes Mellitus and Accelerated Biological Aging in Middle-Aged and Elderly Women.

Bin Wang, Ningjian Wang, Xin Yin, Yuhui Huang, Guoqi Yu, Jiaxi Yang, Yap Seng Chong, Yingli Lu, Michelle A Williams, Frank B Hu, Cuilin Zhang.

OBJECTIVE: To evaluate the association between gestational diabetes mellitus (GDM) and accelerated biological aging in middle-aged and elderly women.
RESEARCH DESIGN AND METHODS: We included parous women with a baseline survey on history of GDM and biological aging biomarkers from the UK Biobank. Information regarding prior GDM was collected via a touchscreen questionnaire and linkage to hospital admission records. Biological aging was evaluated using validated phenotypic age (PhenoAge) based on chronological age and nine biomarkers measured at baseline (2006-2010). Biological aging acceleration was determined as the residual by regressing PhenoAge estimates on chronological age. All-cause mortality and incident cardiometabolic disease during follow-up were also assessed.
RESULTS: Among the 178,363 women (mean age, 57.0 [SD 7.9] years), 1,141 had a history of GDM. In a multivariable-adjusted model, a history of GDM was associated with an increase in PhenoAge acceleration by 2.34 (95% CI 2.02, 2.66) years. The association persisted regardless of the occurrence of type 2 diabetes and related comorbidities after GDM. Consistent results were observed across subgroups, while the GDM-related PhenoAge acceleration was more prominent among women with less physical activity and obesity (both Pinteraction < 0.01). The mediation analysis demonstrated that PhenoAge acceleration explained 57.0% (95% CI 21.0, 86.9), 12.4% (7.3, 20.4), and 21.9% (14.0, 32.5) of the positive associations between GDM and all-cause mortality, type 2 diabetes, and cardiovascular disease, respectively.
CONCLUSIONS: Women with a history of GDM were biologically older than their non-GDM counterparts. The biological aging acceleration partially accounted for the associations between GDM and adverse health outcomes.

DOI: https://doi.org/10.2337/dc25-1842
Cell Rep Med. 2025 Dec 16. pii: S2666-3791(25)00554-3. [Epub ahead of print]6(12): 102481

Association of female reproductive traits with altered aging trajectories: Insights from genetic and observational analyses.

Chen Lou, Guiquan Wang, Zuquan Xiong, Yingxin Celia Jiang, Yan Li, Ming Zhu, Haiyan Yang, Lin Wang, Liying He, Hsun-Ming Chang, Jia Wang, Wencheng Zhu, Xi Dong, Terytty Yang Li, Shuai Yuan, Yue Zhao, Liangshan Mu.

  Women's reproductive health plays a pivotal role in both longevity and the aging process. We conduct Mendelian randomization (MR) and observational analyses to investigate these relationships. Univariate MR analyses reveal that older age at first birth, later menarche, higher estradiol, and sex hormone-binding globulin (SHBG) increase longevity, while pre-eclampsia liability decreases longevity. Older ages at first birth and at first sexual intercourse are associated with lower DNAmGrimAgeAccel, but these associations disappear after mutual adjustment. Mediation analyses identify cardiometabolic diseases, lung diseases, and mental disorders as key mediators. In corroborating the MR results, observational analyses show that early reproductive behaviors, such as age at first sex, are associated with accelerated biological aging. Additionally, we observe significant non-linear associations between hormone levels, age at menopause, and aging outcomes. This study highlights the impact of reproductive health on aging and suggests potential strategies for promoting healthy aging in women.

Keywords:  Mendelian randomization; biological aging; female reproductive traits; longevity; observational analysis

DOI:  https://doi.org/10.1016/j.xcrm.2025.102481
Ibrain. 2025 ;11(4): 457-475

The mechanisms in glucose metabolism of aging hippocampus.

Rui He, Fuxing Zhao, Zhiyu Yang, Tingting Wang, Yaohui Zhang, Jinglan Quan, Gaohong Zhu.

  With the intensification of the aging society, the incidence of various neurodegenerative diseases is on the rise. The hippocampus is susceptible to age-related neuronal decline and is the earliest and crucial region affected in the transition from healthy aging to neurodegenerative diseases. Before the diagnosis of neurodegenerative diseases, there is already a decline in brain energy metabolism, with the disruption of energy metabolism serving as the primary mechanism leading to neuronal damage. This triggers complex signaling mechanisms both inside and outside the brain during the aging process. Glucose serves as the primary energy source for brain tissues, and a decrease in glucose metabolism is an early indicator of age-related functional changes in the brain. Therefore, understanding the pathophysiological basis of glucose metabolism in the aging hippocampus, as well as the underlying mechanisms, is crucial in comprehending cognitive aging. Such understanding is integral for early intervention and the mitigation of memory and learning impairments caused by energy metabolism. In this review, we have delved into the characteristics of energy metabolism, focusing specifically on glucose metabolism, as well as exploring the molecular foundations and associated mechanisms present within hippocampal neuronal cells under both normal and aging conditions. Notably, our investigation has highlighted the vital roles played by ALG5 and STT3A, key molecules involved in N-glycosylation, in influencing GLUT expression and the rate of membrane transport, regulating glucose metabolism, and thereby influencing cellular glucose uptake. The exploration of this study direction holds considerable promise for future endeavors.

Keywords:  ALG5; STT3A; aging; glucose metabolism; hippocampus

DOI:  https://doi.org/10.1002/ibra.12201