TRAM Postdoctoral Training Program

Mobility loss: A “Giant of Geriatrics”
As the late Professor Benard Isaacs detailed in his classic book, “The Challenge of Geriatric Medicine,” immobility, instability, incontinence and intellectual impairment constitute the foundation of geriatrics that continues to this day. These “giants of geriatrics” are all connected, progressive, and caused by multiple factors and have no simple cure. Since its inception in 1992, significant strides have been made in the measurement of mobility, identifying predictors of mobility loss and conceptual models that help explain loss of the mobility. Despite these advancements, mobility loss continues to lack clinical attention, robust biomedical targets, objectively-measured surveillance systems, and effective treatments.

As a result, mobility difficulty has remained persistently high and stagnant since it was systematically measured in the late 1980’s. Currently, 30% of Americans aged 60-69, 40% of individuals aged 70-79, and 55% of individuals age 80 or older report difficulties with their mobility (e.g. walking and climbing stairs).7 Society costs are also significant. Medicare beneficiaries who report difficulties walking a quarter-mile have $42 billion in additional health care costs and over 2 million more hospitalizations than those without limitations.

Focus on Mobility is Ideal for Basic, Translational and Intervention Research.
Moving freely and easily through space only occurs when the coordinated effort between these systems occurs efficiently alongside environmental demands.

Four major themes idealize the study of “mobility” as a translational discipline:
1) spatiotemporal dynamics of movement are dictated through the metabolic energy and force transfer;
2)mobility is impacted by the physical environment an individual’s ability to adapt;
3)mobility control is organized through a neural-mediated feedback and feedforward pattern; 4)musculoskeletal and cardiopulmonary physiology are strongly connected to whole-body mechanics.

These themes speak to the notion that mobility loss truly requires an interdisciplinary approach. Mobility deficits may originate from a systemic process, a universal molecular process, or in specific organ systems that include muscular, skeletal, brain, peripheral nervous, respiratory and circulatory systems. The scientific challenge is that a culmination of these factors are likely to be involved.

TRAM exploits this complexity by defining mechanistic research not only on biological underpinnings (e.g. autophagy, molecular clocks, longevity genes), but also sub-clinical factors (e.g. human brain inter-network interactions) while also considering the influence of disease in a geroscience-like approach. Fortunately for our goal, all species have some form of mobility/locomotion that is quantifiable. It is not surprising that many fundamental discoveries, such as cytochromes in winged insects and skeletal remodeling, were due to understanding an animal’s mobility. Studying mobility provides a “hard” quantifiable outcome for translating new interventions from clinical, psychosocial, physiological and/or pre-clinical origins.

Mobility Loss: Reversible, but Limited Interventions.
Our doctrine is that mobility loss is a preventable chronic condition rather than an irreversible consequence of aging and comorbidity. Investigators at the Institute on Aging (IOA) and involved program faculty are at the forefront for testing and discovering the underlying causes and new interventions for preventing and rehabilitating the loss in mobility in clinical and pre-clinical models. As evidence of this ideology, the LIFE trial definitively demonstrated that a structured moderate-intensity physical activity program reduced the risk of major mobility disability in 1635 vulnerable older adults. We continued this endeavor in the ENabling Reduction of low-Grade Inflammation in SEniors (ENRGISE, AG050499) where 289 persons were enrolled with mobility limitations and elevated IL-6 and mobility limitations. Unfortunately, neither fish oil and losartan, alone or in combination, reduced inflammation nor improved walking speed, compared to placebo.

We continue this pursuit in our other active intervention-based studies (REVIVE, SPICE, OPTIMIZE, RESTORES, UCOPE) by targeting biological processes, behaviors (nutrition + exercise) and psychosocial factors that are known to impact mobility. We also discover new risk factors for mobility loss in our active and recently completed observational studies (Mind in Motion, SOMMA, ChoresXL, PECAN, PEAKS, ROAMM, UpFRONT, Sepsis- Induced Frailty).

TRAM will follow its doctrine by creating a workforce of scientists who develop mobility-related interventions by targeting hallmark age-related biological targets, physiological underpinnings, and psychosocial and neurodegenerative processes.