bims-minfam 2025-01-12 papers

Issue of 2025–01–12
three papers selected by
Ayesh Seneviratne, McMaster University

Exp Hematol. 2025 Jan 07. pii: S0301-472X(25)00002-5. [Epub ahead of print] 104711

How age affects human hematopoietic stem and progenitor cells and strategies to mitigate HSPC aging.

Xueling Li, Jianwei Wang, Linping Hu, Tao Cheng.

Hematopoietic stem cells (HSCs) are central to blood formation and play a pivotal role in hematopoietic and systemic aging. With aging, HSCs undergo significant functional changes, such as an increased stem cell pool, declined homing and reconstitution capacity, and skewed differentiation towards myeloid and megakaryocyte/platelet progenitors. These phenotypic alterations are likely due to the expansion of certain clones, known as clonal hematopoiesis (CH), which leads to disrupted hematopoietic homeostasis, including anemia, impaired immunity, higher risks of hematological malignancies, and even associations with cardiovascular disease, highlighting the broader impact of HSC aging on overall health. HSC aging is driven by a range of mechanisms involving both intrinsic and extrinsic factors, such as DNA damage accumulation, epigenetic remodeling, inflammaging and metabolic regulation. In this review, we summarize the update understanding of age-related changes in HSPCs and the mechanisms underlie the aging process in mammalian models, especially in human study. Additionally, we provide insights into potential therapeutic strategies to counteract aging process and enhance HSC regenerative capacity, which will support therapeutic interventions and promote healthy aging.

DOI: https://doi.org/10.1016/j.exphem.2025.104711

Cells. 2024 Dec 18. pii: 2101. [Epub ahead of print]13(24):

Dog Aging: A Comprehensive Review of Molecular, Cellular, and Physiological Processes.

Gabriella Guelfi, Camilla Capaccia, Martina Tedeschi, Antonello Bufalari, Leonardo Leonardi, Beniamino Cenci-Goga, Margherita Maranesi.

The aging process is a multifactorial biological phenomenon starting at birth and persisting throughout life, characterized by a decline in physiological functions and adaptability. This decline results in the diminished capacity of aging organisms to respond to environmental changes and stressors, leading to reduced efficiency in metabolic, immune, and hormonal functions. As behavioral flexibility wanes, older individuals face longer recovery times and increased vulnerability to diseases. While early research proposed nine core hallmarks of mammalian aging, recent studies have expanded this framework to twelve key characteristics: epigenetic changes, genomic instability, telomere shortening, loss of proteostasis, altered metabolism, mitochondrial dysfunction, cellular senescence, disrupted intercellular communication, stem cell depletion, immune system dysfunction, accumulation of toxic metabolites, and dysbiosis. Given the growing interest in the aging area, we propose to add a new hallmark: impaired water homeostasis. This potential hallmark could play a critical role in aging processes and might open new directions for future research in the field. This review enhances our understanding of the physiological aspects of aging in dogs, suggesting new clinical intervention strategies to prevent and control issues that may arise from the pathological degeneration of these hallmarks.

Keywords: aging dog; aging hallmarks; epigenetic changes; physiological decline

DOI: https://doi.org/10.3390/cells13242101

EClinicalMedicine. 2024 Aug;74 102753

Clonal hematopoiesis of indeterminate potential and the risk of pulmonary embolism: an observational study.

Qianwei Liu, Karin Ekström Smedby, Huiwen Xue, Tove Wästerlid, Jiong Li, Fang Fang, Xinyuan Liu.

Background: Pulmonary embolism causes a substantial burden of morbidity and mortality. Although there are several well-established risk factors for pulmonary embolism, a substantial proportion of cases cannot be attributed to provoked or known risk factors. Accumulating evidence has suggested an association of clonal hematopoiesis of indeterminate potential (CHIP) with the risk of arterial thromboembolism. However, the association between CHIP and the risk of pulmonary embolism remains unknown.
Methods: We performed a community-based cohort study (between 2006 and 2022) including 464,417 individuals with available whole exome sequencing (WES) data in the UK biobank (UKB) to examine the association between CHIP and pulmonary embolism. CHIP was ascertained by analyzing WES data. We used Cox regression models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to assess the association between CHIP and pulmonary embolism. In addition, we performed analyses for several types of CHIP mutations, including DNMT3A, TET2, ASXL1, PPM1D, SRSF2, and JAK2.
Findings: The study included 14,418 individuals with CHIP and 449,999 individuals without CHIP. The median age at cohort entry was 58 and 63 years among individuals without and with CHIP, respectively. We observed an increased risk of pulmonary embolism (HR 1.17, 95% CI, 1.05-1.31) among individuals with CHIP. The increased risk was mainly noted for CHIP with TET2 (HR 1.42, 95% CI 1.16-1.74) or JAK2 (HR 4.17, 95% CI 2.09-8.35) mutation, but not for DNMT3A mutation (HR 1.01, 95% CI 0.86-1.19), ASXL1 mutation (HR 1.15, 95% CI 0.83-1.60), PPM1D mutation (HR 1.22, 95% CI 0.66-2.27), or SRSF2 mutation (HR 0.62, 95% CI 0.20-1.93).
Interpretation: Our results highlight the association of pulmonary embolism in individuals with CHIP, especially the TET2-mutant or JAK2-mutant CHIP. If further studies will identify a causal relationship between clonal hematopoiesis and pulmonary embolism, prioritizing early screening for pulmonary embolism in individuals with CHIP could be significantly beneficial.
Funding: Initial Founding for High Level Talented Scholars in Nanfang Hospital, Southern Medical University (No. 2023G001) and the Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University (Grant No. 2023J009).

Keywords: Clonal hematopoiesis; Cohort study; Epidemiology; Pulmonary embolism

DOI: https://doi.org/10.1016/j.eclinm.2024.102753