Biology of Healthy Aging Laboratory at Johns Hopkins University

Frailty, its identification, treatment, and prevention, is often considered the major reason that geriatric medicine exists. Frailty is present in nearly one out of every six non-institutionalized older adults in the United States (Bandeen-Roche et al., 2015), and contributes to marked vulnerability to physical and mental health issues, geriatric syndromes such as falls and incontinence, medical emergencies, and complications following illnesses and procedures (Fried et al., 2001; Makary et al., 2010; Afilalo et al., 2014). Therefore, research to better identify impending frailty, determine frailty’s causes, and develop strategies that can successfully delay and treat frailty and its complications holds great promise to add healthy years of life for older adults.

Frailty research has experienced major growth over the past several decades. Particularly active and needed areas of research include the following.


Many assessments have been proposed to identify frail older adults, both formal and ad hoc. The assessments have large differences among them and may not identify similar individuals as frail. Whether using or constructing an assessment method, then, it is crucial to understand what is the attribute that the method aims to measure. Reflecting on the purpose of the frailty measurement—for example, case finding versus screening versus risk prediction—also can help.

Biological Basis of Frailty

Research evidences that physical frailty reflects a general age-related decline in the physiology and stress response systems that governs overall health and well-being.   It is hypothesized that many chronic illnesses as well as functional and cognitive decline evolve from this age-related alteration in biology.   At the base of these physiological changes are multiple fundamental (molecular and cellular) biological changes (Walston, 2015; Walston et al., 2019).  DNA damage, cell senescence, protein homeostasis changes, and altered mitochondrial and stem cell function all likely play some role in the evolution of physical frailty, geriatric syndromes, and some chronic disease states.  These molecular and cellular changes contribute to the physiological system dysfunction often observed in frailty, which includes chronic inflammation, hormonal dysregulation, and impairment in energy regulation.   This section provides an overview of physiologic as well as molecular and cellular processes that influences frailty in older adults.  The first section will detail an area where there has been extensive previous study; chronic inflammation.  In addition, a mouse model of frailty, which is based on the evolution of chronic inflammation with increasing age, is described with the goal of wider propagation of the model for research into the biology of frailty.


Recent national estimates are that nearly 1 in 6 older adults is frail (Bandeen-Roche et al., 2015): the associated burden of chronic disease, disability and adverse health events on individuals, families and communities will be enormous (Ortman et al., 2014). Frailty is more prevalent in racial and ethnic minority populations and in those with low income, and in some specific geographic areas of the US.  Better understanding frailty epidemiology can help target treatment and prevention strategies to subgroups and regions where help is most needed.


Interventions that can delay, prevent or treat frailty hold tremendous promise to lessen older adults’ disease and disability burden, lengthen healthy life, and reduce health care costs. Exercise, nutrition, and tailored geriatric care models have been implemented with some success to date (Walston et al., 2018).  However,  further study of these strategies and best deployment practices, as well as the further development of interventions targeting biological mechanisms and psychosocial/environmental contributors are also needed.    


We seek not only to prevent frailty but to promote resilience–a state in which older adults are able to better tolerate medical or psychological stressors–and then bounce back to essentially the same level of health they started out with (Varadhan et al., 2018). Resilience may reflect a high level of fitness in the same biology and physiology whose degradation leads to frailty. To date, resilience in aging is only superficially understood: It has become an extremely active area of research in recent years.