# Ageing Through the Looking‐Glass: The Different Flavours of Clonal Haematopoiesis

**Authors:** Jasmine Singh, David J. Curtis, Le Thi Phuong Thao, Erica M. Wood, Zoe K. McQuilten

PMC · DOI: 10.1111/acel.70425 · Aging Cell · 2026-02-22

## TL;DR

Clonal haematopoiesis, a result of aging, is linked to various age-related diseases and reflects genomic instability.

## Contribution

The paper explores the intersections of different forms of clonal haematopoiesis and their implications for understanding the biology of aging.

## Key findings

- Different forms of clonal haematopoiesis share common risk factors and disease associations.
- Clonal haematopoiesis may exacerbate normal aging features like inflammageing and immunosenescence.

## Abstract

Clonal haematopoiesis (CH) is the presence of acquired mutations in blood cells and is a consequence of ageing that is linked to malignancy, cardiovascular disease and other diseases of ageing. CH is a reflection of genomic instability with ageing; however, there is evidence that CH may exacerbate features of normal ageing, including inflammageing and immunosenescence, and more directly contribute to disease causation. CH can manifest as mosaic loss of X or Y, autosomal mosaic chromosomal rearrangements, or point mutations or small insertions or deletions. Until recently, little has been known about the relationship between different forms of CH and other biomarkers of ageing, including whether they are more likely to co‐exist, whether they work synergistically to promote clonal expansion, and whether they have independent impacts on risk of clinical outcomes. Defining the overlap between different forms of CH and other markers of ageing is important to understand the biological processes involved in ageing, and the mechanisms underlying the associations with diseases of ageing. Here we provide an overview of the current literature on intersections of different forms of CH, the clinical implications of these, and a perspective on how CH enhances our understanding of the biology of ageing.

Different forms of CH share common germline and environmental risk factors and have overlapping prevalence and disease associations, suggesting common underlying ageing processes. We explore intersections of different forms of CH, clinical implications of these, and how this enhances our understanding of the biology of ageing.

## Linked entities

- **Diseases:** malignancy (MONDO:0004992), cardiovascular disease (MONDO:0004995)

## Full-text entities

- **Genes:** TET2 (tet methylcytosine dioxygenase 2) [NCBI Gene 54790] {aka IMD75, KIAA1546, MDS}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, U2AF1 (U2 small nuclear RNA auxiliary factor 1) [NCBI Gene 7307] {aka FP793, RN, RNU2AF1, U2AF35, U2AFBP}, Tet2 (tet methylcytosine dioxygenase 2) [NCBI Gene 214133] {aka Ayu17-449, E130014J05Rik, mKIAA1546}, Dnmt3a (DNA methyltransferase 3A) [NCBI Gene 13435] {aka MmuIIIA}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, POT1 (protection of telomeres 1) [NCBI Gene 25913] {aka CMM10, CRMCC3, GLM9, HPOT1, PFBMFT8, TPDS3}, IL6R (interleukin 6 receptor) [NCBI Gene 3570] {aka CD126, HIES5, IL-1Ra, IL-6R, IL-6R-1, IL-6RA}, SRSF2 (serine and arginine rich splicing factor 2) [NCBI Gene 6427] {aka PR264, SC-35, SC35, SFRS2, SFRS2A, SRp30b}, Il1 (interleukin 1 complex) [NCBI Gene 111343] {aka Il-1}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, MPL (MPL proto-oncogene, thrombopoietin receptor) [NCBI Gene 4352] {aka C-MPL, CD110, MPLV, THCYT2, THPOR, TPOR}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, TCL1A (TCL1 family AKT coactivator A) [NCBI Gene 8115] {aka TCL1}, ASXL1 (ASXL transcriptional regulator 1) [NCBI Gene 171023] {aka BOPS, MDS}, SF3B1 (splicing factor 3b subunit 1) [NCBI Gene 23451] {aka Hsh155, MDS, PRP10, PRPF10, SAP155, SF3b155}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, BRCC3 (BRCA1/BRCA2-containing complex subunit 3) [NCBI Gene 79184] {aka BRCC36, C6.1A, CXorf53}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, SETBP1 (SET binding protein 1) [NCBI Gene 26040] {aka MRD29, SEB}, Il20 (interleukin 20) [NCBI Gene 58181] {aka If2d, Zcyto10}, PPM1D (protein phosphatase, Mg2+/Mn2+ dependent 1D) [NCBI Gene 8493] {aka IDDGIP, JDVS, PP2C-DELTA, WIP1}, Ntn1 (netrin 1) [NCBI Gene 18208] {aka Netrin-1}
- **Diseases:** CHIP (MESH:D056005), myeloid disorders (MESH:D007951), gout (MESH:D006073), coronary heart disease (MESH:D003327), liver disease (MESH:D008107), Chronic inflammation (MESH:D007249), neurodegenerative diseases (MESH:D019636), non-haematological diseases (MESH:D004194), uniparental disomy (MESH:D024182), peripheral vascular disease (MESH:D016491), liver fibrosis (MESH:D008103), X-chromosome loss (MESH:D040181), chronic kidney disease (MESH:D051436), Alzheimer's dementia (MESH:D000544), mCAs (MESH:D002869), cancers (MESH:D009369), lymphopenia (MESH:D008231), diabetes (MESH:D003920), congenital dyskeratosis (MESH:C565079), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MESH:D056648), COPD (MESH:D029424), acute kidney injury (MESH:D058186), stroke (MESH:D020521), steatohepatitis (MESH:D005234), Werner's syndrome (MESH:D014898), obesity (MESH:D009765), autoimmune diseases (MESH:D001327), organ dysfunction (MESH:D009102), damage (MESH:D020263), VAF (MESH:D006316), neurological disorders (MESH:D009461), CH (MESH:C580365), myelodysplastic syndrome (MESH:D009190), blood and solid organ cancer (MESH:D019337), impaired neutrophil (MESH:C564275), death (MESH:D003643), Streptococcus pneumoniae  infection (MESH:D011008), blood (MESH:D006402), atherosclerosis (MESH:D050197), LOY (MESH:C536297), venous thrombosis (MESH:D020246), insulin resistance (MESH:D007333), osteoporosis (MESH:D010024), clonal abnormalities (MESH:D000090362), infection (MESH:D007239), cardiovascular disease (MESH:D002318), AML (MESH:D054218), ischaemic stroke (MESH:D002544), impaired immune function (MESH:D007154), Leukaemia (MESH:D015458), Anaemia (MESH:D000743), dementia (MESH:D003704), coronary artery disease (MESH:D003324), lymphoid malignancies (MESH:D008223), venous thrombo-embolism (MESH:D004617), inflammatory bowel disease (MESH:D015212), heart failure (MESH:D006333), CCUS (MESH:D065309), aneuploidy (MESH:D000782), cognitive impairment (MESH:D003072)
- **Chemicals:** 5-methylcytosine (MESH:D044503), cytosine (MESH:D003596), cholesterol (MESH:D002784), polycyclic aromatic hydrocarbons (MESH:D011084), navitoclax (MESH:C528561), 5-hmC (MESH:C011865), CHIP (-), Canakinumab (MESH:C541220), lipid (MESH:D008055), reactive oxygen species (MESH:D017382), alcohol (MESH:D000438)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], gut metagenome (species) [taxon 749906]
- **Mutations:** JAK2 V617F, Asp358Ala
- **Cell lines:** mLOY — Mus musculus (Mouse), Mouse adrenal cortical carcinoma, Cancer cell line (CVCL_0585)

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12928004/full.md

## References

180 references — full list in the complete paper: https://tomesphere.com/paper/PMC12928004/full.md

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Source: https://tomesphere.com/paper/PMC12928004