Unveiling aging dynamics in the hematopoietic system insights from single-cell technologies

Jin, Xinrong; Zhang, Ruohan; Fu, Yunqi; Zhu, Qiunan; Hong, Liquan; Wu, Aiwei; Wang, Hu

doi:10.1093/bfgp/elae019

Cited by 2 publications

(1 citation statement)

References 145 publications

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“…Another study identified a distinct expression pattern of circular RNAs (circRNAs) between frail and robust elderly individuals, highlighting their potential as biomarkers for frailty [ 32 ]. Innovations in single-cell RNA sequencing have enabled the comprehensive profiling of immune cells across various conditions, revealing an age-dependent accumulation of transcriptome heterogeneity in immune cells and identifying specific transcription factors and distinct cellular trajectories associated with aging [ 59 , 60 ]. Furthermore, a frailty-specific monocyte subset characterized by the high expression of the long noncoding RNAs NEAT1 and MALAT1 provides new insights into immune senescence [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Oxidative Stress Regulates FOXP3+ T-Cell Activity and CD4-Mediated Inflammation in Older Adults with Frailty

Gill,

Bansal,

Guo

et al. 2024

IJMS

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In healthy older adults, the immune system generally preserves its response and contributes to a long, healthy lifespan. However, rapid deterioration in immune regulation can lead to chronic inflammation, termed inflammaging, which accelerates pathological aging and diminishes the quality of life in older adults with frailty. A significant limitation in current aging research is the predominant focus on comparisons between young and older populations, often overlooking the differences between healthy older adults and those experiencing pathological aging. Our study elucidates the intricate immunological dynamics of the CD4/Treg axis in frail older adults compared to comparable age-matched healthy older adults. By utilizing publicly available RNA sequencing and single-cell RNA sequencing (scRNAseq) data from peripheral blood mononuclear cells (PBMCs), we identified a specific Treg cell subset and transcriptional landscape contributing to the dysregulation of CD4+ T-cell responses. We explored the molecular mechanisms underpinning Treg dysfunction, revealing that Tregs from frail older adults exhibit reduced mitochondrial protein levels, impairing mitochondrial oxidative phosphorylation. This impairment is driven by the TNF/NF-kappa B pathway, leading to cumulative inflammation. Further, we gained a deeper understanding of the CD4/Treg axis by predicting the effects of gene perturbations on cellular signaling networks. Collectively, these findings highlight the age-related relationship between mitochondrial dysfunction in the CD4/Treg axis and its role in accelerating aging and frailty in older adults. Targeting Treg dysfunction offers a critical basis for developing tailored therapeutic strategies aimed at improving the quality of life in older adults.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Oxidative Stress Regulates FOXP3+ T-Cell Activity and CD4-Mediated Inflammation in Older Adults with Frailty

Gill,

Bansal,

Guo

et al. 2024

IJMS

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Genomic instability and genetic heterogeneity in aging: insights from clonal hematopoiesis (CHIP), monoclonal gammopathy (MGUS), and monoclonal B-cell lymphocytosis (MBL)

Kallai,

Ungvari,

Fekete

et al. 2024

GeroScience

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Aging is a multifaceted process characterized by a gradual decline in physiological function and increased susceptibility to a range of chronic diseases. Among the molecular and cellular mechanisms driving aging, genomic instability is a fundamental hallmark, contributing to increased mutation load and genetic heterogeneity within cellular populations. This review explores the role of genomic instability and genetic heterogeneity in aging in the hematopoietic system, with a particular focus on clonal hematopoiesis of indeterminate potential (CHIP), monoclonal gammopathy of undetermined significance (MGUS), and monoclonal B-cell lymphocytosis (MBL) as biomarkers. CHIP involves the clonal expansion of hematopoietic stem cells with somatic mutations. In contrast, MGUS is characterized by the presence of clonal plasma cells producing monoclonal immunoglobulins, while MBL is characterized by clonal proliferation of B cells. These conditions are prevalent in the aging population and serve as measurable indicators of underlying genomic instability. Studying these entities offers valuable insights into the mechanisms by which somatic mutations accumulate and drive clonal evolution in the hematopoietic system, providing a deeper understanding of how aging impacts cellular and tissue homeostasis. In summary, the hematopoietic system serves as a powerful model for investigating the interplay between genomic instability and aging. Incorporating age-related hematological conditions into aging research, alongside other biomarkers such as epigenetic clocks, can enhance the precision and predictive power of biological age assessments. These biomarkers provide a comprehensive view of the aging process, facilitating the early detection of age-related diseases and hopefully enabling personalized healthcare strategies.

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Unveiling aging dynamics in the hematopoietic system insights from single-cell technologies

Cited by 2 publications

References 145 publications

Mitochondrial Oxidative Stress Regulates FOXP3+ T-Cell Activity and CD4-Mediated Inflammation in Older Adults with Frailty

Mitochondrial Oxidative Stress Regulates FOXP3+ T-Cell Activity and CD4-Mediated Inflammation in Older Adults with Frailty

Genomic instability and genetic heterogeneity in aging: insights from clonal hematopoiesis (CHIP), monoclonal gammopathy (MGUS), and monoclonal B-cell lymphocytosis (MBL)

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