age-associated changes in hematopoiesis

^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]

Introduction

The hematopoietic system undergoes change with aging.

decreased bone marrow reserves
diminished reticulocytosis in response to erythropoietin
age-related defects in lymphopoiesis
increased incidence of myeloid myelodysplasia & myeloid leukemia^[5]^[7]
increased incidence of polycythemia vera, thrombocythemia, & myelofibrosis
increased plasma hepcidin levels in older patients may be associated with anemia of chronic inflammation^[6]

hematopoiesis in adults <65 years of age is massively polyclonal^[9]
in adults >75 years, 30-60% of haematopoiesis is accounted for by 12-18 independent clones, each contributing 1-34% of blood production^[9]
- most clones had begun their expansion before age 40 years
  - only 22% with known driver mutations
- loss of the Y chromosome confers a selective benefits in males

anemia in the very old is associated with increased mortality independent of comorbidites^[5]^[6]

↑ Essentials of Clinical Geriatrics, 4th ed, Kane RL et al (eds) McGraw Hill, NY, 1999
↑ UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
↑ The Merck Manual of Geriatrics, 3rdh ed, Merck & Co, Rahway NJ, 2000
↑ Taffet GE, Physiology of Aging, In: Geriatric Medicine: An Evidence-Based Approach, 4th ed, Cassel CK et al (eds), Springer-Verlag, New York, 2003
↑ ^5.0 ^5.1 ^5.2 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
↑ ^6.0 ^6.1 ^6.2 den Elzen WP, Willems JM, Westendorp RG et al Effect of anemia and comorbidity on functional status and mortality in old age: results from the Leiden 85-plus Study. CMAJ. 2009 Aug 4;181(3-4):151-7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19635749
↑ ^7.0 ^7.1 Estey E. Acute myeloid leukemia and myelodysplastic syndromes in older patients. J Clin Oncol. 2007 May 10;25(14):1908-15. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17488990
↑ Ferrucci L, Semba RD, Guralnik JM et al Proinflammatory state, hepcidin, and anemia in older persons. Blood. 2010 May 6;115(18):3810-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20081092
↑ ^9.0 ^9.1 ^9.2 Mitchell E, Spencer Chapman M, Williams N et al. Clonal dynamics of haematopoiesis across the human lifespan. Nature 2022. 606, 343-350 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35650442 PMCID: PMC9177428 Free PMC article https://www.nature.com/articles/s41586-022-04786-y