Issue Guest Editors:

Atsushi Iwama, MD, PhD, The University of Tokyo (Japan) and Anthony D. Ho, MD, Heidelberg University (Germany).

The exponential growth of the aging population presents a significant global challenge. Promoting healthy aging largely depends on maintaining a robust hematopoietic and immune system, which is crucial for protecting against infections and cancer. Since Till and McCulloch's [1] groundbreaking discovery of hematopoietic stem cells (HSCs) in bone marrow (BM) in 1961, extensive research has focused on preserving the functional integrity of HSCs throughout life [2]. The interactions between HSCs and their BM niche are fundamental to this effort [3,4].

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Bone marrow niches for hematopoietic stem cells in homeostasis and aging

Taichi Nakatani, Takashi Nagasawa

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Among various types of candidate cells, including osteoblasts and Nestin+ periarteriolar cells, several lines of histological and genetic evidence have demonstrated that the single population of mesenchymal stem cells, termed CXC chemokine ligand 12 (CXCL12)–abundant reticular (CAR) cells, which overlap strongly with leptin receptor–expressing (LepR+) cells, is the major cellular component of niches for hematopoietic stem cells (HSCs) and hematopoiesis in the bone marrow (BM). Expression of p16, a marker for senescent cells, and interleukin (IL)-1β and γH2AX foci, a marker for DNA damage, were increased in CAR/LepR+ cells and osteoblasts with age.

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

Xueling Li, Jianwei Wang, Linping Hu, Tao Cheng

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Hematopoietic stem cells (HSCs) are at the apex of the hematopoietic hierarchy, with the ability of self-renew and differentiation into all the mature cells downstream. They continuously provide the body with fresh blood cells throughout the lifetime. The interaction between hematopoietic system aging and systemic aging has long been a topic of significant interest. In 2005, Conboy et al. [1] demonstrated that the blood of young mice could promote the regeneration of muscle tissue and hepatocytes in aged mice through a parabiosis model, suggesting the presence of specific molecules in young blood capable of reversing aging.

Reconsidering the usual suspects in age-related hematologic disorders: is stem cell dysfunction a root cause of aging?

Foteini Fotopoulou, Esther Rodríguez-Correa, Charles Dussiau, Michael D. Milsom

Open Access

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The global trend toward an increasing aged population demographic raises significant societal challenges, particularly concerning health. As organisms age, progressive tissue dysfunction increases the risk of a broad range of diseases. The hematopoietic system, with its wide range of cell types and physiological functions, is especially vulnerable to the effects of aging [1]. An increased susceptibility to infections is one of the most prominent problems with regards to age-related mortality and morbidity, attributed primarily to the impaired function of the adaptive immune system [2].

Novel techniques to quantitatively assess age-dependent alterations in biophysical properties of HSPCs and bone marrow niche

Anthony D. Ho, Motomu Tanaka

Open Access

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Hematopoietic stem and progenitor cells (HSPCs) are responsible for the lifelong maintenance of blood cell production, a process that relies on the precise regulation of self-renewal versus differentiation of the primitive HSPCs [1]. The decline in the ability of HSPCs to regenerate as we age has been linked to changes in how HSPCs interact with their microenvironment in the bone marrow [2,3]. The negative impact on the regenerative potential of HSPCs with age is therefore a sum product of interactions between HSPCs with extracellular matrix (ECM) and other neighboring cells in the bone marrow niche [4–6].

Microbiome and Hemato-immune Aging

Alban Johansson, Nicole Pui-Yu Ho, Hitoshi Takizawa

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The microbiome is a highly complex and diverse symbiotic component that undergoes dynamic changes with the organismal aging. Microbial perturbations, termed dysbiosis, exert strong influence on dysregulating the bone marrow niche and subsequently promoting the aging of hematopoietic and immune system. Accumulating studies have revealed the substantial impact of intestinal microbiome on the initiation and progression of age-related hematologic alteration and diseases, such as clonal hematopoiesis and blood cancers.

Biomarkers for aging of blood – how transferable are they between mice and humans?

Vithurithra Tharmapalan, Wolfgang Wagner

Open Access

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Mouse models have provided invaluable insights into the aging process due to their genetic similarity to humans, sharing approximately 99% of genes and many comparable gene expression patterns [1,2]. Aging in mice mirrors many aspects of human aging, including loss of regenerative potential, hair graying, cognitive and motor impairment, and various age-associated diseases [1]. This similarity extends to the hematopoietic system, which in both species shows reduced capacity for generation and homeostasis restoration after injury or stress [3].