Stress-Induced Aging: Investigating Chronic Wound Stress as a Catalyst for Systemic Aging and Functional Decline

Stress-Induced Aging: Investigating Chronic Wound Stress as a Catalyst for Systemic Aging and Functional Decline Chronic wounds, defined by delayed healing and frequent recurrence, often manifest in adulthood due to complex factors that disrupt normal repair and impose sustained physiological stress on the body. These wounds share biological features associated with aging, such as cellular senescence, chronic inflammation, epigenetic alterations, stem cell depletion, and extracellular matrix dysfunction. However, it remains unclear whether the local repeated stress of chronic wounds contributes to systemic aging, although individuals with chronic wounds often exhibit aging-associated characteristics like frailty, muscle weakness, reduced mobility, and impaired immunity. In this project, we hypothesize that prolonged exposure to recurrent wound stress in adulthood accelerates both molecular and functional aging. The study will be conducted in two phases. In the R61 phase, we will establish a mouse model simulating chronic wound stress across different adult life stages and assess the impact on aging hallmarks and functional decline. This model will allow us to investigate and measure biological aging changes, such as senescence and inflammation, and physical outcomes, including frailty and sarcopenia. The R33 phase will examine how pre-existing frailty exacerbates aging in the context of chronic wounds, using hind-limb suspension to mimic physical frailty. Additionally, we will test interventions—senolytics, anti-inflammatory agents, and exercise—to mitigate molecular and functional aging. This research aims to establish chronic wound stress as a driver of aging and identify therapeutic targets to improve resilience and functional outcomes in adults burdened by chronic wounds. Project Number: 1R61AG096091-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Daniel Roh (+2 co-PIs) | Institution: BOSTON UNIVERSITY MEDICAL CAMPUS, BOSTON, MA | Award Amount: $686,700 | Activity Code: R61 | Study Section: Special Emphasis Panel[ZAG1 ZIJ-3 (M1)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11229151