Rising Star Presentation: Dr. Brianne Connizzo

Aging Tendons Lack Adaptive Responses to Mechanical Loading

ABSTRACT

Much like cars and homes, tissues in the body require daily maintenance to ensure proper structure and function, a process called extracellular matrix (ECM) remodeling. This process is essential for repairing both daily damage and large-scale injuries, and it is performed primarily by resident cell types within each tissue. While it’s well known that aging is associated with chronic declines that lead to loss of function and disease, how and why this occurs is still unknown. By using in vitro explant models that maintain cells in their native microenvironment, we explore the ability of cells to sense and respond to macroscopic tissue loading and investigate the fine balance between adaptive and degenerative extracellular matrix remodeling. Our work reveals over multiple studies that aging tissues exhibit an inability to adapt to changing functional demands, tipping the balance towards matrix breakdown over synthesis. More recently, we have shown that key cell functions, such as metabolic dysfunction and cellular senescence, are directly linked to this dysfunctional ECM turnover and could unlock doors to preventing or treating chronic tissue breakdown. Ultimately, we aim to identify points of intervention or potential therapeutic strategies to prevent or treat age-related tendon degeneration, such that we can maintain healthy and active lifestyles for longer.