Sundar Srinivasan, Ph.D.
Department of Orthopaedics and Sports Medicine
E-mail: sundars@u...


TITLE:

"Bottom-up Exploration of Bone Mechanotransduction and its Age-Related Degradation"


ABSTRACT:

Mechanical loading of the skeleton, as occurs during physical activity,
is a critical determinant of bone structure and morphology.  Further,
"extra" loading of the skeleton is anabolic (e.g., weight lifting, tennis)
and can be used to augment bone mass and strength.  Given the promise
of physical exercise, mechanical loading represents a noninvasive means
to counteract increased skeletal fragility associated with aging and
menopause.  However, the promise of physical exercise has remained
unrealized, in part because aging degrades a number of cellular functions
involved in bone mechanotransduction (or how cells perceive and initiate
biochemical cascades in response to the stimulus).  In this seminar, I will
present our research exploring mechanotransduction as a bottom-up
adaptive process using a unique technique called agent-based modeling.
In an ongoing effort, we have developed a model of cellular signaling
pathways activated acutely by mechanical stimuli (order of mins), that is
surprisingly effective and accurate in simulating and predicting bone tissue
adaptation that un-folds 3-wks downstream.  Further, the model is sufficient
and capable of simulating the aging-related diminishment in the responsiveness
of the skeleton to physical exercise and has suggested interventions (that we
are testing) that could potentially overcome age-related deficits in
mechanotransduction function.