Studying the Foundations of Aging in Hematologic Disease

Hematologic disorders disproportionately affect older adults. However, the understanding of how aging influences these conditions is insufficient. Researchers in the geroscience field are investigating geriomics to better understand the implications of aging on the development and treatment of hematologic disorders.

“Placing the Brakes on Accelerated Aging,” one of the Special Scientific Symposia at the 66th American Society of Hematology Annual Meeting and Exposition, will highlight biologic aging assessments for hematologic diseases. Three geroscience experts will present at the session, which is chaired by Ashley Rosko, MD, a professor in the clinical division of hematology and medical director of oncogeriatrics at The Ohio State University in Columbus, Ohio.

Here, Dr. Rosko previews the session that will explore how and why geriomics is being studied to distinguish biologic from chronologic aging.

Ashley Rosko, MD

“Biologic aging assessments for hematologic disease will be crucial for understanding and appropriately treating aging patients, along with facilitating the translation of emerging new therapies to target or attenuate aging mechanisms to treat hematologic diseases,” Dr. Rosko said.

Who should attend this session?

Physicians, scientists, and allied health professionals who are interested in understanding the intersection of hematology and aging should attend this session. This session is meant to help attendees understand the critical underpinnings of aging in hematologic disease.

Who will be speaking and what perspectives will they offer?

Els Mansell, PhD, is an assistant professor in the Department of Hematology at Erasmus Medical Center in Rotterdam, Netherlands. Dr. Mansell’s research is focused on inflammation and metabolic determinants (mitochondrial activity) in relationship to hematopoietic cell physiology. Dr. Mansell’s presentation, “Aging of Hematopoietic Stem Cells and Their Niche,” will focus on hematopoietic stem cell aging and its relationship to hematologic disease.

Christin Burd, PhD, is a scientist in the Departments of Molecular Genetics and Cancer Biology and Genetics at The Ohio State University. Dr. Burd’s research program is focused on the regulation of p16INK4a expression in cancer and aging. Her ongoing work, funded by the National Institutes of Health (NIH), is focused on the role of age-related p16INK4a expression in T-cell function and immunotherapeutic response. Dr. Burd is a member of the Scientific Advisory Board of the American Federation for Aging Research and has served as a consultant to the NIH’s National Institute on Aging. In “Geroscience and Geri-Omics in Hematologic Malignancies,” Dr. Burd will present her work on integrating biomarkers of aging in hematologic malignancies for toxicity and tolerance.

Marcel van den Brink, MD, PhD, is the president of City of Hope Los Angeles and City of Hope National Medical Center and is a global expert in immuno-oncology. Dr. van den Brink is widely recognized for his work in immune reconstitution and translational science for bone marrow transplant. In “Targeting Rejuvenation Therapies to Decelerate Aging,” Dr. van den Brink will discuss T-cell regeneration after significant physiologic stress (transplant, chemotherapy, cellular therapy) with a focus on the aging host and mechanisms to explore T-cell reconstitution in older patients.

Can you elaborate on how geriomics may aid in distinguishing biologic and chronologic aging?

The concept of geriomics is to leverage multiple “omic” fields of science and technology to gain insight into biologic mechanisms of aging and identify potential interventions to attenuate or reverse age-related conditions. The “hallmarks of aging” integrate genomics, proteomics, metabolomics, transcriptomics, and more to understand the biologic processes contributing to the aging process.

In addition, other modalities include imageomics and technologic measures to understand and gauge physiologic aging. Clinicians also have robust clinical measures of physiologic aging, outside of chronologic age, to gauge health. Examples include standardized geriatric assessments measuring objective measures of function (Timed Up and Go test, Short Physical Performance Battery), screening for memory impairment, functional assessments (activities of daily living, instrumental activities of daily living), polypharmacy (drug-drug interactions, duplicates, etc.), and nutritional impairments (mini nutritional assessment, food insecurity).

Identifying and integrating these measures may yield a better signature or phenotype of biologic or physiologic age.

Why are biologic aging assessments needed for hematologic diseases, and what are their benefits?

Biomarkers of aging are being investigated to predict age-related outcomes and identify factors associated with aging and the disease itself. There are no current guidelines, from the U.S. Food and Drug Administration or the European Medicines Agency, for standardizing the development, measurement, or validation of biomarkers of aging. However, there is significant interest in understanding biomarkers of aging that may reflect the accumulated effect of experience and exposures in a lifetime. This special symposium seeks to review many of these markers relevant to hematologic disease.

There are numerous unanswered questions in hematology regarding accelerated aging, mechanisms of disease and aging development, and, importantly, how we can intervene to improve patient outcomes to slow or attenuate age-related disease.

Aging results in a time-dependent accumulation of damage that leads to loss of resilience, functional decline, changes in phenotype over a lifetime, and increased probability of disease. Within the hematopoietic stem cell niche, we are learning more about hematopoietic stem cell cycling, quiescence, and age-associated features that decrease function or promote inflammation or dysregulation within the hematopoietic microenvironment that leads to hematologic disease.

What do you hope attendees will take away?

The special symposium seeks to understand many of the biologic underpinnings of aging in hematologic disease, examine recent evidence to support biomarkers of aging in hematologic disease, and look toward new interventions to ameliorate age-related declines.

This session will be particularly important for scientists to look at their work through the lens of biologic aging and how to take a fresh approach to age-old questions.