We are pleased that De Alfieri and colleagues share our interest in physical resilience and, like us, are intrigued by the opportunities for future research in this area. They offer the reasonable hypothesis that some cases of remarkable recovery in chronically ill patients who are hospitalized with acute illness are attributable not only to psychological fortitude but also to “spontaneous abilities,” which they refer to as biologic resilience. In our working model, we define physical resilience at the whole-person level as one’s ability to maintain or recover function after exposure to a stressor, and we propose that one important component of physical resilience is physiologic (or biologic) reserve. We agree with De Alfieri’s suggestion that the biological profile most likely to drive effective recovery is characterized by systems that are “flexible and adaptable enough to cope with change of any kind.” We use the term “physiologic reserve” to capture the notion that resilient cells, organs, and tissues must have a capacity to enhance or adapt their activity beyond a baseline level when they are faced with conditions of higher demand. This notion seems to be very similar to the concept that De Alfieri and colleagues have labeled “biologic resilience.” Whatever we call it, we agree that it is critically important to understand, at a biological and physiological level, those factors that enable the aging human body to respond adaptively and appropriately when faced with inevitable stressors.
We certainly agree with the suggestion that a promising avenue for research on this topic is to focus on older adults during hospitalization for an acute illness, in order to identify biological or laboratory-based “protective factors” associated with better functional outcomes. Of course, future observational studies of this kind must take into account the severity and intensity of the stressor, which includes not only the acute illness that led to hospitalization but also (to use De Alfieri’s words) the “stressors and chaos suffered during hospitalization.” Quantifying the amount of stress inflicted by a particular acute care episode is not a simple problem, but it is an issue that this field will have to grapple with. Another important issue that remains to be clarified is the relative importance of and potential synergy between various domains or systems that may contribute to physical resilience. That knowledge gap is likely to frustrate efforts to develop a tool to measure resilience at the whole-person level.
We also agree that more work is needed to “go beyond static biomarkers” in order to develop tools that reflect the “dynamic properties of homeostatic regulatory systems.” We believe that one of the most clinically relevant contributions that could stem from research on late-life physical resilience is the development of safe, reliable stress tests that reveal the dynamic potential (or reserve) of various organ systems. Such stress tests may inform therapeutic decision making (e.g., “which chemotherapy regimen is likely to be better tolerated by this patient with multiple comorbidities?”) or help to personalize successful aging programs that aim to enhance every patient’s chances of a resilient response when faced with acute insults, recognizing that many stressors in life are unplanned.