bims-minfam 2025-03-09 papers

Issue of 2025–03–09
four papers selected by
Ayesh Seneviratne, McMaster University

Physiology (Bethesda). 2025 Feb 28.

Metabolic alterations in HSCs during aging and leukemogenesis.

Yi-Hsuan Chiang, Stephan Emmrich, Nicola Vannini.

Aging is a multifaceted process associated with a functional decline in cellular function over time, affecting all lifeforms. During the aging process, metabolism, a fundamental hallmark of life (1), is profoundly altered. In the context of hematopoiesis, the proper function of hematopoietic stem cells - at the apex of the blood system - is tightly linked to their energy metabolism, which in turn shapes hematopoietic output. Here, we review the latest developments in our understanding of the metabolic states and changes in aged hematopoietic stem cells, molecular players and pathways involved in aged hematopoietic stem cell metabolism, the consequences of perturbed metabolism on clonal hematopoiesis and leukemogenesis, and pharmacologic/ genetic strategies to reverse or rejuvenate altered metabolic phenotypes.

Keywords: aging; clonal hematopoiesis; hematopoietic stem cell; leukemogenesis; metabolism

DOI: https://doi.org/10.1152/physiol.00054.2024

Nat Aging. 2025 Mar 06.

Mitochondria-enriched hematopoietic stem cells exhibit elevated self-renewal capabilities, thriving within the context of aged bone marrow.

Haruhito Totani, Takayoshi Matsumura, Rui Yokomori, Terumasa Umemoto, Yuji Takihara, Chong Yang, Lee Hui Chua, Atsushi Watanabe, Takaomi Sanda, Toshio Suda.

The aging of hematopoietic stem cells (HSCs) substantially alters their characteristics. Mitochondria, essential for cellular metabolism, play a crucial role, and their dysfunction is a hallmark of aging-induced changes. The impact of mitochondrial mass on aged HSCs remains incompletely understood. Here we demonstrate that HSCs with high mitochondrial mass during aging are not merely cells that have accumulated damaged mitochondria and become exhausted. In addition, these HSCs retain a high regenerative capacity and remain in the aging bone marrow. Furthermore, we identified GPR183 as a distinct marker characterizing aged HSCs through single-cell analysis. HSCs marked by GPR183 were also enriched in aged HSCs with high mitochondrial mass, possessing a high capacity of self-renewal. These insights deepen understanding of HSC aging and provide additional perspectives on the assessment of aged HSCs, underscoring the importance of mitochondrial dynamics in aging.

DOI: https://doi.org/10.1038/s43587-025-00828-y

Semin Cancer Biol. 2025 Feb 27. pii: S1044-579X(25)00029-X. [Epub ahead of print]111 89-114

Clonal hematopoiesis, cardiovascular disease and cancer treatment-induced cardiotoxicity.

Nan Zhang, Xu Tian, Dongkun Sun, Gary Tse, Bingxin Xie, Zhiqiang Zhao, Tong Liu.

Clonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells is derived from a single hematopoietic stem cell lineage. It is considered to be a premalignant state that predisposes individuals to an increased risk of cancers. Recently, emerging evidence has demonstrated a strong association between CH and both the incidence and mortality of cardiovascular diseases (CVD), with the relative risks being comparable to those attributed to traditional cardiovascular risk factors. In addition, CH has been suggested to play a role in CVD and anti-cancer treatment-related cardiotoxicity amongst cancer survivors. Moreover, certain forms of chemotherapy and radiation therapy have been shown to promote the clonal expansion of specific CH-related mutations. Consequently, CH may play a substantial role in the realm of cardio-oncology. In this review, we discuss the association between CH with cancer and CVD, with a special focus on anti-cancer treatment-related cardiotoxicity, discuss possible future research avenues and propose a systematic approach for clinical practice.

Keywords: Cancer survivor; Cardio-oncology; Cardiotoxicity; Clonal hematopoiesis; Clonal hematopoiesis of indeterminate potential

DOI: https://doi.org/10.1016/j.semcancer.2025.02.007

Nat Aging. 2025 Mar 04.

The complex interplay between aging and cancer.

Lucrezia A Trastus, Fabrizio d'Adda di Fagagna.

Cancer is an age-related disease, but the interplay between cancer and aging is complex and their shared molecular drivers are deeply intertwined. This Review provides an overview of how different biological pathways affect cancer and aging, leveraging evidence mainly derived from animal studies. We discuss how genome maintenance and accumulation of DNA mutations affect tumorigenesis and tissue homeostasis during aging. We describe how age-related telomere dysfunction and cellular senescence intricately modulate tumor development through mechanisms involving genomic instability and inflammation. We examine how an aged immune system and chronic inflammation shape tumor immunosurveillance, fueling DNA damage and cellular senescence. Finally, as animal models are important to untangling the relative contributions of these aging-modulated pathways to cancer progression and to test interventions, we discuss some of the limitations of physiological and accelerated aging models, aiming to improve experimental designs and enhance translation.

DOI: https://doi.org/10.1038/s43587-025-00827-z