Age-Related Frailty: A Clinical Model for Geroscience?

Abstract

In their everyday practice, geriatricians are confronted with the fact that older age and multimorbidity are associated to frailty. Indeed, if we take the example of a very old person with no diseases that progressively becomes frail with no other explanation, there is a natural temptation to link frailty to aging. On the other hand, when an old person with a medical history of diabetes, arthritis and congestive heart failure becomes frail there appears an obvious relationship between frailty and comorbidity. The unsolved question is: Considering that frailty is multifactorial and in the majority of cases comorbidity and aging are acting synergistically, can we disentangle the main contributor to the origin of frailty: disease or aging? We believe that it is important to be able to differentiate age-related frailty from frailty related to comorbidity. In fact, with the emergence of geroscience, the physiopathology, diagnosis, prognosis and treatment will probably have to be different in the future.

Frailty and the risk of dementia: is the association explained by shared environmental and genetic factors?

“…A 6-month intervention based on group exercise, nutritional supplementation, depression management, deprescribing medications, and home hazard reduction showed sustained beneficial effects on frailty up to 1 year [ 37 ]. Moreover, as frailty can present both in the absence and presence of multimorbidity, disease management may be more beneficial to those living with comorbidities, while slowing down cellular aging might benefit those whose frailty is driven by accelerated biological aging rather than age-related diseases [ 38 ]. A geroscience hypothesis posits that targeting fundamental aging processes at the cellular level might delay the onset or severity of multiple chronic diseases and frailty [ 38 , 39 ].…”

Proteomics and Epidemiological Models of Human Aging

“…In this kind of frailty model, statisticians translate the heterogeneity by specifying multivariate failure time conditional on an unobserved construct, frailty, which can be both group and subject-specific. Other authors proposed that frailty is characterized by increased individual vulnerability to endogenous and exogenous stressors from agingassociated decline in reserve and function across multiple physiological systems (Xue, 2011;Buta et al, 2016;Takeda et al, 2020). The concept of frailty later evolved from a statistical construct to a clinical entity, and several operational definitions were proposed in the literature and generated a robust discussion in the field.…”

“…Beyond inflammation and obesity, no risk factor for multimorbidity development has been identified to date. With an improvement in high-throughput -omics technology, including transcriptomics, proteomics and metabolomics, can provide critical detailed studies on the molecular and biological processes that change with age, unveiling underlying mechanisms that drive multiple chronic conditions and frailty, and ideally facilitating the identification of the new effective approaches for prevention and treatment (da Costa et al, 2016;Takeda et al, 2020).…”

COVID19 Vaccination in Frail People. Lots of Hope and Some Questions

“…Human aging is characterized by physical and physiological changes that reduce the immune system and modulate vaccine responses (5,6). Whether the coming COVID vaccine will generate an effective response in the oldest and frail older people and how these responses will be modulated by age or other clinical factors such as frailty is currently an open question.…”