bims-mithem 2025-10-26 papers

Issue of 2025–10–26
five papers selected by
Tim van Tienhoven, Erasmus Medical Center

Cell Cycle. 2025 Oct 24. 1-24

Advances in DNA damage repair mechanisms in stem cells and their applications.

Dongxu Wei, Yuhao Chang, Yao Yang, Xuanbai Chen, Shiqi Jin, Kainan Huang, Zeyidan Jiapaer, Xianli Wang.

Stem cells play a critical role in tissue regeneration and the maintenance of homeostasis. Due to their high replicative potential, stem cells face an elevated risk of DNA damage during DNA replication. Consequently, efficient DNA damage repair (DDR) mechanisms are essential for preserving the genomic stability and functionality of stem cells. This review summarizes the main DNA damage repair mechanisms, examines the characteristics of these DDR pathways in different stem cell types (highlighting their specific features and key molecules), and discusses the clinical significance and applications of stem cell DDR research. Furthermore, we identify current research limitations and propose potential future research directions. Collectively, this review provides a comprehensive perspective on DDR mechanisms in stem cells, laying a foundation for future investigations and potential clinical applications.

Keywords: DNA damage; DNA double-strand break repair; DNA repair; Stem cells; base excision repair; cell-specific DDR-associated molecular regulators; interstrand cross-link repair; mismatch repair; nucleotide excision repair; translesion DNA synthesis

DOI: https://doi.org/10.1080/15384101.2025.2576514

Front Cell Dev Biol. 2025 ;13 1590524

Mitochondrial dysfunction in age-related sarcopenia: mechanistic insights, diagnostic advances, and therapeutic prospects.

Yingtao Huang, Chenchen Wang, Haijian Cui, Guangjiang Sun, Xiaonan Qi, Xiaosheng Yao.

Sarcopenia is a progressive age-related decline in skeletal muscle mass, strength, and function, representing a significant health burden in older adults. Diagnostic criteria have been established that integrate measures of muscle mass, strength, and physical performance [e.g., European Working Group on Sarcopenia in Older People 2010 (EWGSOP1) and 2019 (EWGSOP2) criteria]. Mechanistically, sarcopenia is driven by hormonal changes, chronic inflammation, cellular senescence, and, importantly, mitochondrial dysfunction. Age-related declines in sex hormones and activation of myostatin impair muscle regeneration and metabolism, while chronic low-grade inflammation disrupts protein synthesis and accelerates proteolysis via the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP). The accumulation of senescent cells and their secretory phenotype further exacerbates muscle degeneration and functional decline. Mitochondrial dysfunction plays a central role, characterized by impaired biogenesis, excessive reactive oxygen species (ROS) production, compromised autophagy/mitophagy, and accumulation of mitochondrial DNA (mtDNA) mutations. These defects collectively disrupt muscle energy homeostasis, promoting atrophy. The AMPK/SIRT1/PGC-1α and mTORC1 signaling pathways, along with PINK1/Parkin-mediated and receptor-dependent mitophagy, are essential for regulating mitochondrial biogenesis, protein synthesis, and mitochondrial quality control. Current and emerging therapeutic approaches include resistance and endurance exercise, nutritional and pharmacological agents targeting mitochondrial health, and hormonal modulation. Innovative treatments such as senolytics, exerkines, and gene therapies show promise but require further validation. Future advances in mechanistic understanding, diagnostics, and therapeutic strategies offer hope for mitigating sarcopenia and improving the quality of life in aging populations.

Keywords: aging; chronic inflammation; mitochondrial dysfunction; muscle atrophy; sarcopenia; therapeutic strategies

DOI: https://doi.org/10.3389/fcell.2025.1590524

Cell Death Dis. 2025 Oct 21. 16(1): 745

P-selectin overexpression impairs hematopoietic stem cell homeostasis via inflammatory receptor-mediated proliferation and differentiation.

Wei He, Huandi Qiu, Yunyu Feng, Qiang Qiu, Li Zheng, Cong Pan, Xue Cui, Yuanyuan Sun, Bochuan Wang, Yiguo Hu.

Hematopoietic stem cells (HSC) sustain lifelong blood and immune system homeostasis. This study identifies P-selectin as a pivotal regulator of HSC function under aging and inflammatory stress. We observed pronounced Selp upregulation in aged HSC and inflammatory contexts, which drives excessive proliferation and differentiation while depleting their long-term self-renewal capacity. Using tissue-specific Selp overexpression models, we demonstrate that chronic Selp elevation disrupts HSC polarity, promotes oxidative stress accumulation, and induces genomic instability. Over time, sustained Selp expression leading to LT-HSC exhaustion and impaired hematopoietic reconstitution. Single-cell transcriptomics revealed that Selp enforces a pro-inflammatory transcriptional program in HSC, hyperactivating IFN-γ and PI3K-AKT-MOTR signaling pathways. Mechanistically, P-selectin directly interacted with IFNγR1 on the HSC surface, which driving activation of JAK1-STAT1 and PI3K-AKT-mTOR signaling axes. Notably, Selp overexpression suppresses the pathogenic capacity of leukemia stem cells (LSC), highlighting potential therapeutic implications. Our findings established P-selectin as a molecular nexus linking chronic inflammation and aging to hematopoietic decline, with dual therapeutic implications: targeting P-selectin may mitigate age-related hematopoietic dysfunction while offering a strategy to selectively impair LSC activity in malignancies.

DOI: https://doi.org/10.1038/s41419-025-08050-9

Sage Open Aging. 2025 Jan-Dec;11:11 30495334251385836

Effects of Participation in Volunteer Activities on CD34+ Hematopoietic Stem Cells.

Chuan-Hsin Chang, Chia-Chi Chen, Yue-Cune Chang, Cho Chen Hsieh, Chai Ching Lin, Jia-Fu Lee.

Aging populations face health challenges, and volunteering may improve health outcomes. This study investigated the relationship between volunteering, CD34+ hematopoietic stem cells, and health indicators in older adults. The sample included 91 participants aged 65 to 75, with 52 reporting prior volunteering involvement. Evaluations comprised the Geriatric Depression Scale (GDS), Mini-Mental State Examination, Clinical Dementia Rating scale, and Neuropsychiatric Inventory. Blood analyses measured CD34+ hematopoietic stem cells and CD34+ lymphocytes. Multiple linear regression assessed variations in CD34+ counts and related metrics among groups, adjusting for confounding factors. Volunteers exhibited enhanced cognitive functioning and lower depression levels compared to non-volunteers, as reflected in GDS scores of 4.29 ± 4.18 versus 8.26 ± 5.09 (p < .001). Furthermore, volunteers had notably elevated CD34+ stem cell and lymphocyte counts, suggesting volunteering positively influences this health marker. Participation in volunteer activities is linked to improved cognitive abilities, reduced depressive symptoms, and heightened CD34+ hematopoietic stem cell levels. Findings underscore the potential health benefits of volunteering for older adults, necessitating further investigation into the mechanisms and enduring effects of volunteerism on health, with CD34+ cell counts identified as a significant biomarker for cognitive and emotional health enhancements in this population.

Keywords: CD34+; effects; hematopoietic stem cells; volunteer activities

DOI: https://doi.org/10.1177/30495334251385836

Immunol Med. 2025 Oct 21. 1-24

Long COVID: mechanisms of disease, multisystem sequelae, and prospects for treatment.

Seiya Oba, Tadashi Hosoya, Hideyuki Iwai, Shinsuke Yasuda.

Long COVID has emerged as a significant global health issue, affecting individuals across a wide spectrum of initial disease severity. While its definition and prevalence vary across studies, persistent symptoms such as fatigue, cognitive dysfunction, respiratory difficulties, and cardiovascular complications have been widely reported. Multiple pathophysiological mechanisms have been proposed, including incomplete viral clearance, reactivation of latent viruses, immune dysregulation, autoimmunity, endothelial dysfunction, microbiome alterations, and mitochondrial impairment. These interconnected processes are thought to contribute to chronic inflammation and multi-organ disease. To date, there are no established therapies for Long COVID, and management primarily focuses on symptomatic relief and rehabilitation. Vaccination has been shown to reduce the incidence of Long COVID, and emerging strategies, including antiviral agents, immune-modulating therapies, microbiome restoration, and mitochondria-targeted interventions, are under investigation. This review summarizes the current understanding of the epidemiology, pathophysiology, organ-specific manifestations, and potential therapeutic approaches for Long COVID, aiming to provide insights into future research directions and clinical management strategies.

Keywords: COVID-19; Long COVID; disease mechanism; post-acute COVID-19 syndrome; post-acute sequelae of SARS-CoV-2 infection

DOI: https://doi.org/10.1080/25785826.2025.2570902