Report: NIA Workshop on Measures of Physiologic Resiliencies in Human Aging

“In addition to these illustrative examples, it is likely that many other basic mechanisms implicated in the biology of aging (18,19), may individually or collectively influence physiologic resilience.”

“Studies on frailty in older persons, which has been associated with impairments in some types of resilience (eg, postsurgical outcomes) (15) suggest that at a minimum five major, interconnected physiologic domains may influence degree of resilience: autonomic nervous system, hypo-thalamic-pituitary…”

“The possibility of shared physiologic mechanisms responsible for decrements in multiple types of resilience is of particular interest (13).”

“Conversely, the concept of allostatic load (9), suggests that repeated or chronic stress may result in “wear and tear” on neural and endocrine systems over time, with potentially negative effects on resilience.”

“…role of resilience as long-term predictors comes from studies on the relationship of alterations in stability of blood pressure and gait to risk of future adverse clinical and functional outcomes, and studies on heart-rate recovery following a 400 m walk as a predictor of long-term mortality (22).”

“Time series analyses can distinguish patterns that reflect the integration and correlation of multiple inputs over different scales in time or space (eg, fractal patterns) from those that are random, lacking any functional connection among them (eg, white noise) (17).”

“Population heterogeneity in such studies provides opportunities to increase the specificity of understanding of resilience factors, for example, to identify which components of physical activity may confer greater resilience to a given stressor (21).”

“Recently, physical resilience at the whole person level has been defined as a characteristic which determines one’s ability to resist or recover from functional decline following a health stressor(s) (2).”

“A considerable amount of research has focused on the influence of psychosocial factors on resilience to age-related social and behavioral stressors and (to a lesser degree) health-related stressors (4,5).”

“A mouse model of chronic inflammation with a variety of frailty-associated phenotypes (29) could yield insights into the role of these factors in resiliencies.”

“However, results of tests combining cognitive and physical activity stresses to date have not found them clearly superior to single-task tests in predicting falls (25,26) or discriminating between persons with and without cognitive impairment (27,28).”

“However, results of tests combining cognitive and physical activity stresses to date have not found them clearly superior to single-task tests in predicting falls (25,26) or discriminating between persons with and without cognitive impairment (27,28).”

“This workshop followed a 2014 NIA-sponsored workshop on resilience in laboratory animals (6,7), which focused principally on identifying tests of key aspects of resilience that could serve as predictive markers for assessing candidate interventions that target fundamental aging processes with…”

“Resilience, the ability to resist or recover from adverse effects of a stressor, has been of widespread interest in numerous areas of social, psychologic, biologic, and medical research (1,2) and may be considered as the opposite of vulnerability (3).”

“Prior stress exposures may enhance reserve and resilience through an anamnestic immune response as occurs following vaccination or via hormesis, a term used to refer to the ability of substances normally viewed as toxins to generate beneficial effects at very low concentrations (8).”

“These features are shared in age-related changes in responses to differing SNS stressors (eg, orthostasis and glucose load), and responses of other homeostatic regulatory systems, for example, the hypotha-lamic-pituitary axis (6,11).”

“However, results of tests combining cognitive and physical activity stresses to date have not found them clearly superior to single-task tests in predicting falls (25,26) or discriminating between persons with and without cognitive impairment (27,28).”

“Age-related impairments in feedback loops may also be related to exaggerated stimulus responses of some regulatory factors and delays in return to baseline levels , for example, attenuated and delayed glucose recovery post-insulin challenge (14) or dysregulated cortisol patterns (10).”

“However, results of tests combining cognitive and physical activity stresses to date have not found them clearly superior to single-task tests in predicting falls (25,26) or discriminating between persons with and without cognitive impairment (27,28).”

“Multiple contributors to resiliencies may also serve as redundant systems, with some components becoming more active in the case of deficiency in others (16).”

“The presence of multiple contributory stressors implies a need for a broader range of predictive tests that simulate simultaneous or sequential stressor exposures and compare their combined physiologic or functional effects with those of individual stressors (24).”

“Single-cell measurements collected during functional challenges may also reveal the dynamics of perturbation and subsequent return to homeostasis necessary to evaluate “resilience” in a given cell type (Kirkland et al. 2016; Hadley et al. 2017).”

“Physical resilience is a new concept in the field of geriatrics introduced by the National Institute on Aging (NIA)[18]; it is defined as the ability to recover from physically or psychologically traumatic events [19].”