Unexplained Anemia in Older Persons: Elucidating Etiologies, Improving Diagnoses, and Identifying and Testing Potential Treatment Strategies

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Topic Description

Post Date: May 11, 2026

Expiration Date: May 11, 2028

Purpose 

This topic is highlighted to encourage research to improve understanding of clinical, mechanistic, etiologic, diagnostic, and therapeutic considerations regarding the substantial proportion of anemic older persons whose anemia is currently not explained by existing diagnostic categories. This understanding may lead to more effective treatments for these individuals, which could reduce anemia-related morbidities and improve functional abilities and quality of life.   

Background and Scientific Context

Anemia is common in the older population. Roughly 17% of people aged 65 and over are anemic, and anemia is cited as a contributing cause of death in about 10% of U.S. death certificates. Yet in 30–50% of older adults with anemia, the cause remains undetermined, a condition referred to as unexplained anemia of aging (UAA). Thus, UAA constitutes an important unmet clinical problem in gerontology and hematology. To address this, the National Institute on Aging convened a 2024 workshop to synthesize knowledge about UAA and identify future research directions, in which experts in aging, hematology, and related fields reviewed epidemiology, biological mechanisms, clinical implications, and research opportunities to improve understanding of UAA. A workshop summary has been published (El Kassar N et al. A proposed path to explaining the unexplained anemia of aging. J Gerontol, Series A: Biol Sci Med Sci 2026, 81(1) doi.org/10.1093/gerona/glaf251).

Elucidating the etiologies that contribute to currently unexplained anemia in older persons may enhance diagnostic methods, selection of appropriate interventions, and development of new interventions to target these etiologies.  Several causal factors have been proposed, including effects of age-related changes in inflammatory factors, cellular senescence, age-related changes in level and activity of sex hormones, age-related changes in the microbiome, and clonal hematopoiesis, as well as interactive effects of known and novel risk factors that can occur in the presence of multimorbidity, which is very prevalent among older persons. 

A variety of research strategies may contribute to elucidation, diagnosis, and treatment of specific causes of currently unexplained anemia in older persons. Epidemiologic and clinical studies may identify subgroups of currently unexplained anemia differing in natural history, risk factors, and profiles of multimorbidity, and identify high-risk groups for specific types of anemia. Pathophysiologic studies, including use of in vitro novel alternative methods, may identify specific cellular, tissue, and systemic mechanisms, and provide a basis for better diagnostic characterization of currently unexplained anemias, and selection or design of targeted interventions. Controlled intervention studies may both clarify mechanisms of these anemias and assess the efficacy and safety of novel targeted treatments. 

Participating ICOs

National Institute on Aging (NIA)

NIA is interested in the research topics and strategies described above, including but not limited to: 

  • Epidemiologic and clinical studies to identify subgroups of currently unexplained anemia differing in natural history, risk factors, and profiles of multimorbidity, and identify high-risk groups for specific types of anemia.
  • Pathophysiologic studies, including preclinical studies as well as in vitro novel alternative methods, to identify specific cellular, tissue, and systemic mechanisms. 
  • Assessing sensitivity, specificity, feasibility, and clinical utility of diagnostic approaches to rule out known causes and identify novel subtypes of UAA.
  • Controlled intervention studies to clarify mechanisms contributing to currently unexplained anemia in older persons and/or assess the efficacy and safety of novel targeted treatments.
  • Assessing effectiveness of strategies for screening and recruitment in clinical trials of interventions targeted at specific novel types of anemia in older persons.
ICO Scientific Contact:
Alexis Bakos, PhD, MPH, RN
[email protected]

National Cancer Institute (NCI)

Subtypes of UAA may predict cancer risk and affect cancer treatment outcomes and survivorship of older adults. NCI’s areas of interest in UAA and cancer are:

  • Epidemiological studies to determine if UAA and its subtypes increase cancer risk in older adults and clinical studies to develop prevention strategies to reduce UAA-related cancer risk. 
  • Epidemiological and clinical studies to examine the associations of UAA and its subtypes with post-treatment outcomes among older cancer survivors, including physical functioning, chronic health conditions, second cancers, recurrence, and mortality.
  • Clinical studies to determine the impact of UAA and its subtypes on cancer therapy tolerance, toxicity profiles, and novel strategy development for toxicity management. 
  • Studies to understand the mechanisms to inform strategies to intercept pathways connecting UAA subtypes to cancer initiation, progression, and therapy outcomes using preclinical models and new approach methodologies.    
ICO Scientific Contact:
Weiwei Chen, PhD
[email protected]

Lisa Gallicchio, PhD
[email protected]

Young Kim, Ph.D.
[email protected]

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