Numerous hematologic disorders are attributed to aging hematopoietic stem cells (HSCs) and their reduced differentiation and self-renewal functions. However, recent evidence reveals a strong link between inflammation and accumulation of senescent cells in the tissue, and genetic or pharmacological depletion of senescent cells in animal models results in enhanced regenerative potential of these cells. Likewise, the impact of inflammation on HSC fate and functions has just started to emerge and presents an opportunity to elucidate the underlying mechanisms and selectively target senescent HSCs to improve overall health in aging adults.

The senescence-associated secretory phenotype (SASP) is a key feature of senescent cells, characterized by the secretion of pro-inflammatory cytokines, chemokines, and matrix metalloproteinases. This pro-inflammatory response is linked to aging and the pathogenesis of various diseases, including autoimmune diseases, chronic obstructive pulmonary disease (COPD), cardiovascular disease, obesity, diabetes, inflammatory bowel disease, and cancer. Notably, senescent cells are known to induce senescence of neighboring cells through the SASP, contributing to the amplification of the subsequent inflammatory response through a positive feedback mechanism. Subsequently, the mutation load transmitted from HSCs to daughter cells negatively affects the functional activity of various populations of specialized blood cells.

A significant proportion of aged HSCs also exhibit impaired autophagy, which leads to the accumulation of mitochondria, causing metabolic stress because of high levels of reactive oxygen species. Accumulating mitochondrial DNA mutations cause mitochondrial dysfunction, leading to hematopoietic defects commonly observed in the elderly, and reducing mitochondrial stress can restore stem cell function. Overall, cellular metabolism—regulated by mitochondrial status, reactive oxygen species, and mTOR signaling—plays a crucial role in maintaining HSC function throughout life. The molecular cause of age-related metabolic dysfunction in HSCs remains unclear, but pharmacological interventions targeting these pathways may offer potential for restoring function in aged HSCs.

This workshop is intended to bring leaders from academia, government, and industry together to brainstorm recent advancements and the future outlook of the role of inflammation and senescence in hematologic and cardiovascular diseases and to identify the existing gaps that are limiting progress in the field.

Objectives:

1. To provide a high-level networking and discussion opportunity for researchers and leaders in the area of blood and cardiovascular diseases. 

2. To understand the associations between inflammation and HSC senescence, aging, and dysfunction and their role in hematopoiesis and atherosclerosis.

3. To elucidate the influence of inflammation on HSC fate and function and explore potential therapeutic strategies for the clearance of senescent cells.

Event Details:

Dates: January 20–21, 2026

Virtual Details: A link to join the virtual workshop will be sent to you closer to the workshop. Registration for the workshop is free but required in order to attend.

Agenda:

View the draft agenda.

Contact:

For questions or to request reasonable accommodations to participate in this event, please email Julia D’Albora at julia.d'albora@nih.gov.