Frailty

System Regulation

Human biology consists of building blocks within dynamic systems (such as metabolism or nervous system regulation) and a control network through which these systems are interconnected and regulate each other. Together, these systems enable health and the ability to maintain physiological balance throughout a lifetime of exposures to different stressors. A healthy, vital, and resilient human being is, in part, a result of a well-tuned system that works in split-second synchrony. When the tight mutual regulation becomes less [Page 902]sensitive and effective, the person is less resilient to stressors. It is now shown that these alterations occur progressively over the life course and for some individuals begin as early as one’s 20s and progress over time. This leads to widening disparities in resilience with age and contributes to health disparities between groups. It has been shown that allostatic load, the effects of chronic exposure to high life stress and disadvantage that can begin in childhood, contributes to this dysregulation over the life course and predicts frailty. Ultimately, there are cellular changes that occur with older age that drive the altered function observed in so many physiologic systems, including impaired production of energy and ability to use it. There is marked variability in the rate at which this dysregulation develops across the life course. This variability can be explained by extrinsic exposures such as toxic stress as well as biologic mechanisms such as altered cellular energy production.

Prevalence and Risk

In its late stages, frailty emerges as a distinct state of lower energy reserves and resilience compared to others of the same age or those who are younger. Frailty is apparent in at least 25% of people aged 85 and older, with the frequency steadily increasing after 65–70 years, when it is apparent in about 3% of older adults. It is more frequent in older women than men and occurs at earlier ages in population subsets who experience higher rates of chronic life stress and adversity. Frailty appears to result from biologic aging but also earlier in life from specific diseases with high inflammation such as HIV. There appear to be psychological consequences of the physiologic state of frailty, with frail adults sensing their vulnerability and becoming anxious or depressed. When three to five frailty criteria are present, there is a high risk of death within 3 years for older adults in general as well as people with HIV, chronic kidney disease, or severe burns.

...