Translational research : the journal of laboratory and clinical medicine
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There are over 15 million survivors of cancer in the United States whose rates of frailty, an aging phenotype, range from just under 10% to over 80%. Frailty impacts not only disease survival but also long-term function and quality of life in children, adolescents, and in all adults diagnosed and/or treated for cancer. ⋯ Biological mechanisms responsible for aging and potentially for frailty among individuals with or who have been treated for cancer are discussed. Finally, promising pharmaceutical and lifestyle interventions designed to impact aging rather than a specific disease, tested in other populations, but likely applicable in cancer patients and survivors, are discussed.
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Frailty is a complex late life phenotype characterized by cumulative declines in multiple physiological systems that increases the risk for disability and mortality. The biological changes associated with aging are risk factors for frailty as well as for complex diseases; whereas longevity is assumed to be an outcome of protective biological mechanisms. ⋯ The complexity of these phenotypes and relatively low heritability in studies are the main roadblocks in deciphering genetic mechanisms of these age associated conditions. We review genetic research related to frailty, and discuss the possible intertwined biology of frailty and longevity.
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Frailty is a clinical state of vulnerability to stressors resulting from cumulative alterations in multiple physiological and molecular systems. Frailty assessment in patients with chronic disease is useful for identifying those who are at increased risk for poor clinical and patient reported outcomes. ⋯ Herein, we review the literature and potential pathobiological mechanisms underpinning associations between frailty in lung disease and age, sex, comorbidity and symptom burden, severity of lung disease, inflammatory biomarkers, various clinical parameters, body composition measures, and physical activity levels. We also propose a multipronged program of future research focused on improving the accuracy and precision of frailty measurement in lung disease, identifying blood-based biomarkers and measures of body composition for frailty, determining whether subphenotypes of frailty with distinct pathobiology exist, and developing personalized interventions that target the specific underlying mechanisms causing frailty.
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The human microbiome is constituted by an extensive network of organisms that lie at the host/environment interface and transduce signals that play vital roles in human health and disease across the lifespan. Frailty is a critical aging-related syndrome marked by diminished physiological reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes including death. ⋯ We discuss HIV infection as a key prototype for elucidating the complex pathways via which the microbiome may precipitate frailty. Finally, we review considerations for future research efforts.