Research into the biological basis of frailty has been difficult to accomplish because of a lack of standardized definitions, disease and disability confounders, and complex multifactorial etiology. Multiple physiological systems are likely to be involved, including the skeletal muscle, endocrine, and immune/inflammation systems. Physiological characterization of frail older adults might provide etiologic clues. Translational research programs that connect mechanisms related to aging, such as oxidative damage and telomere shortening, to clinical aging-related syndromes will be necessary to further this critical area of geriatric research.
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