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

Attila Kallai^{1

2}, Zoltan Ungvari^{3

4

5

6

7}, Mónika Fekete¹, Andrea B Maier^{8

9

10

11}, Gabor Mikala^{2

12}, Hajnalka Andrikovics^{1

13}, Andrea Lehoczki^{14

15}

Affiliations

¹ Healthy Aging Program, Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary.
² Doctoral College, Health Sciences Program, Semmelweis University, Budapest, Hungary.
³ Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁴ Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA.
⁵ Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁶ Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁷ Doctoral College/Institute of Preventive Medicine and Public Health, International Training Program in Geroscience, Semmelweis University, Budapest, Hungary.
⁸ Department of Medicine and Aged Care, @AgeMelbourne, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
⁹ Department of Human Movement Sciences, @AgeAmsterdam, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands.
¹⁰ Centre for Healthy Longevity, @AgeSingapore, National University Health System, Singapore, Republic of Singapore.
¹¹ Healthy Longevity Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, @AgeSingapore, National University Health System, Singapore, Republic of Singapore.
¹² Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Budapest, Hungary.
¹³ Laboratory of Molecular Genetics, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Budapest, Hungary.
¹⁴ Healthy Aging Program, Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary. Andrea.M.Lehoczki@gmail.com.
¹⁵ Doctoral College, Health Sciences Program, Semmelweis University, Budapest, Hungary. Andrea.M.Lehoczki@gmail.com.

PMID: 39405013
PMCID: PMC11872960
DOI: 10.1007/s11357-024-01374-y

Review

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

Attila Kallai et al. Geroscience. 2025 Feb.

. 2025 Feb;47(1):703-720.

doi: 10.1007/s11357-024-01374-y. Epub 2024 Oct 15.

Authors

Attila Kallai^{1

2}, Zoltan Ungvari^{3

4

5

6

7}, Mónika Fekete¹, Andrea B Maier^{8

9

10

11}, Gabor Mikala^{2

12}, Hajnalka Andrikovics^{1

13}, Andrea Lehoczki^{14

15}

Affiliations

¹ Healthy Aging Program, Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary.
² Doctoral College, Health Sciences Program, Semmelweis University, Budapest, Hungary.
³ Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁴ Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA.
⁵ Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁶ Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁷ Doctoral College/Institute of Preventive Medicine and Public Health, International Training Program in Geroscience, Semmelweis University, Budapest, Hungary.
⁸ Department of Medicine and Aged Care, @AgeMelbourne, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
⁹ Department of Human Movement Sciences, @AgeAmsterdam, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands.
¹⁰ Centre for Healthy Longevity, @AgeSingapore, National University Health System, Singapore, Republic of Singapore.
¹¹ Healthy Longevity Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, @AgeSingapore, National University Health System, Singapore, Republic of Singapore.
¹² Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Budapest, Hungary.
¹³ Laboratory of Molecular Genetics, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Budapest, Hungary.
¹⁴ Healthy Aging Program, Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary. Andrea.M.Lehoczki@gmail.com.
¹⁵ Doctoral College, Health Sciences Program, Semmelweis University, Budapest, Hungary. Andrea.M.Lehoczki@gmail.com.

PMID: 39405013
PMCID: PMC11872960
DOI: 10.1007/s11357-024-01374-y

Abstract

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.

Keywords: Aging; Biological age; Biomarker; Clock; Mutation.

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Conflict of interest statement

Declarations. Competing interests: Dr. Hajnalka Andrikovics, Dr. Andrea B. Maier, and Dr. Andrea Lehoczki serve as Associate Editor for GeroScience. Dr. Zoltan Ungvari serves as Editor-in-Chief for GeroScience.

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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)

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

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