A proposed path to explaining the unexplained anemia of aging

Approximately 17% of people aged 65 years and older are anemic, and 10% of death certificates report anemia as a secondary cause of death in the United States. Nonetheless, anemia remains unexplained in 30%-50% of older adults. This unexplained anemia of aging (UAA) is a diagnosis of exclusion. The mechanism, impact, and progression of UAA remain unknown. At older ages, anemia adds to pre-existing co-morbidities with significant adverse health consequences, representing a compelling unmet clinical concern. The National Institute on Aging held a workshop in 2024 to discuss current knowledge and research opportunities. Topics included the epidemiology of anemia at older age and its clinical implications; probable mechanism(s) underlying UAA, that is, low-grade inflammation's effects on erythropoiesis; the role of microbiota in iron regulation in bone marrow; the importance of ruling out a diagnosis of leukemic clonal hematopoiesis (CH), which is more prevalent in older age; the role of senescence and aging governing hematopoiesis; and the effects of sex hormones on hematopoietic stem cell aging. Understanding the roles of these factors could reduce the proportion of the older anemic population whose anemia remains unexplained and offer insights into new potential diagnostic and intervention strategies. Speakers reviewed previous clinical trials in patients with UAA and CH. They discussed lessons learned and future research priorities, including efforts to develop new diagnostic algorithms and potential uses of machine learning.

Authors

Institutions

Publication Details

Journal
The Journals of Gerontology Series A
Published
2025-11-09
DOI
https://doi.org/10.1093/gerona/glaf251
Primary Topic
Hemoglobinopathies and Related Disorders
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

A proposed path to explaining the unexplained anemia of aging

William B. Ershler, Maria M. Brooks, Dachuan Zhang, Claudia Großmann et al.
The Journals of Gerontology Series A
Hemoglobinopathies and Related Disorders
article

A proposed path to explaining the unexplained anemia of aging

William B. Ershler, Maria M. Brooks, Dachuan Zhang, Claudia Großmann, Uma Borate, Theodosia A. Kalfa, Isabel Beerman, Kenneth E. White, Kelly L. Bolton, Amy Elizabeth Dezern, Tomas Ganz, Michael Pfeilstöcker, Alain Kuaban, Daisuke Nakada, Mikkael Aaron Sekeres, Janis L. Abkowitz, George A. Kuchel, Andrew Artz, Chengxuan Qiu, Nahed El Kassar, Jennifer L. St. Sauver, Aziz Nazha, Sean X. Leng, Eleanor Marie Simonsick, Luigi Ferrucci
article en

Abstract

Approximately 17% of people aged 65 years and older are anemic, and 10% of death certificates report anemia as a secondary cause of death in the United States. Nonetheless, anemia remains unexplained in 30%-50% of older adults. This unexplained anemia of aging (UAA) is a diagnosis of exclusion. The mechanism, impact, and progression of UAA remain unknown. At older ages, anemia adds to pre-existing co-morbidities with significant adverse health consequences, representing a compelling unmet clinical concern. The National Institute on Aging held a workshop in 2024 to discuss current knowledge and research opportunities. Topics included the epidemiology of anemia at older age and its clinical implications; probable mechanism(s) underlying UAA, that is, low-grade inflammation's effects on erythropoiesis; the role of microbiota in iron regulation in bone marrow; the importance of ruling out a diagnosis of leukemic clonal hematopoiesis (CH), which is more prevalent in older age; the role of senescence and aging governing hematopoiesis; and the effects of sex hormones on hematopoietic stem cell aging. Understanding the roles of these factors could reduce the proportion of the older anemic population whose anemia remains unexplained and offer insights into new potential diagnostic and intervention strategies. Speakers reviewed previous clinical trials in patients with UAA and CH. They discussed lessons learned and future research priorities, including efforts to develop new diagnostic algorithms and potential uses of machine learning.

The Journals of Gerontology Series AVol. 81(1)
Cincinnati Children's Hospital Medical Center (US), City Of Hope National Medical Center (US), Mayo Clinic (US), University of Connecticut (US), Johns Hopkins University (US), University of California, Los Angeles (US), Oregon Health & Science University (US), University of Pittsburgh (US), Baylor College of Medicine (US), Shanghai Jiao Tong University (CN), Washington University in St. Louis (US), American Society of Hematology (US), Inova Fairfax Hospital (US), Karolinska Institutet (SE), Patient-Centered Outcomes Research Institute (US), Fred Hutch Cancer Center (US), Hanusch Hospital (AT), Department of Health (TW), Ministry of Education (TH), Mayo Clinic in Arizona (US), Institute on Aging (US), National Institute on Aging (US), Oregon Health and Science University Hospital (US), Ludwig Boltzmann Institute of Osteology (AT), Mayo Clinic in Florida (US), Institute of Aging (CA), Sylvester Comprehensive Cancer Center (US), Baylor Genetics (US), Sidney Kimmel Comprehensive Cancer Center (US), Indiana University – Purdue University Indianapolis (US), Indiana University (US), UConn Health (US), Incyte (United States) (US)
Openalex Percentile: Top 54%
Hemoglobinopathies and Related Disorders
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.