Dynamic Multi-System Resilience in Human Aging/Studies of Resiliencies to Physiologic Stressors: Need for Multilevel and Life Course Approaches
November 12, 2018
1:00 pm - 1:40 pm
Chhanda Dutta (NIH)
Age-related declines in resiliencies can contribute to a variety of adverse health and functional outcomes in later life. Consequently, it can be more difficult for an older person to recover from acute illnesses or injuries which are otherwise efficiently resolved or overcome by younger individuals. For the purposes of this discussion, resilience is defined as a dynamic property which enables cells, organs, organisms or individuals to resist or recover from the effects of a physiologic/physical stressor. To gain meaningful insight into the various aspects of aging changes in resiliencies to physical stressors, such as the diversity of resilient phenotypes, the underlying protective factors which preserve resilience with aging (or conversely risk factors that contribute to vulnerabilities) and the trajectories of change in these factors with age, it will be important for studies to incorporate multilevel and life course approaches.
Regarding multilevel examinations, examples of clinical assessments which can be leveraged as dynamic measures of resiliencies spanning the whole-body to physiological systems include perturbation tests of balance, assessments of cognitive processing speed following chemotherapy, methacholine tests and tilt-table testing. Yet, the current lack of standardized research tools to probe resiliencies at the cellular level is a major methodological hurdle to research on resiliencies and aging. A crucial feature of such assays will be the ability to quantitatively assess cellular resilience in a person-specific manner. To this end, the literature contains examples of in vitro tests which may be adapted and validated for cellular resiliencies, such as assays of DNA repair capacity to predict sensitivity to chemotherapeutic agents, immune profiling methods to predict recovery post hip replacement, and scratch wound migration assays to predict recovery from surgical procedures. Commonly used in vitro tests of cellular stress responses in biology of aging research (e.g., resistance to oxidative stress, inflammatory cytokine production, activation of anti-apoptotic pathways) may also serve as a basis for the development of standardized assays. Once available, these standardized tests of cellular resilience could be further translated into a novel class of personalized in vitro clinical diagnostics.
Moreover, insight into changes in resiliencies across the human lifespan (a gerontological perspective) could reveal aging mechanisms underlying decrements, as well as factors contributing to the maintenance of resilient phenotypes as we age. Data from the field of regenerative medicine suggest that there may be intrinsic factors present during postnatal growth and development which confer greater resiliency in juveniles compared to adults. Specifically, data generated in various animal models indicate that juvenile organisms possess more robust defense mechanisms and more efficient repair mechanisms (though it is acknowledged that immaturity can also be associated with increased vulnerability). In summary, the characterization of different resilient phenotypes and elucidation of age-related changes in resiliencies to specific stressors and the underlying mechanisms (cellular resiliencies) at different stages of the life span could create new translational research opportunities for the development of novel, targeted interventions to preserve and/or enhance resiliency and for promoting healthy aging in humans.