Emerging roles of frailty and inflammaging in risk assessment of age-related chronic diseases in older adults: the intersection between aging biology and personalized medicine

I-Chien Wu, Cheng-Chieh Lin, Chao A Hsiung, I-Chien Wu, Cheng-Chieh Lin, Chao A Hsiung

Abstract

A chronic disease in older adults usually runs a course that is less predictable than in younger individuals. Unexplained variations in disease incidence, prognosis, therapeutic responses, and toxicity are frequently observed among older adults. This heterogeneity poses huge challenges to the current one-size-fits-all health care systems, and calls for more personalized managements of chronic diseases in older adults. Aging is characterized by progressive deterioration of bodily functions with increasing risk of failure over time. The entire process is hierarchically organized, and progresses from intracellular events to changes at systemic and ultimately organism levels at different rates among different individuals. Aging biology exerts great influences on the development and progression of most age-related chronic diseases. Thus, aging biology could contribute to the complexity of illnesses that increase with age, and aging biomarkers possess a great potential to enable personalized health risk assessment and health care. We review evidences supporting the roles of aging biomarkers in risk assessment of prevalent age-related diseases. Frailty phenotype is an objectively measured indicator of advanced-stage aging that is characterized by organism-level dysfunction. In contrast, altered inflammation markers level signifies an earlier stage between cellular abnormalities and systems dysfunction. Results of human observational studies and randomized controlled trials indicate that these measures, albeit simple, greatly facilitate classification of older patients with cancer, chronic kidney disease, cardiovascular diseases and type 2 diabetes mellitus into groups that vary in disease incidence, prognosis and therapeutic response/toxicity. As the detailed mechanisms underlying the complex biologic process of aging are unraveled in the future, a larger array of biomarkers that correlate with biologic aging at different stages will be discovered. Following the translational research framework described in this article, these research efforts would result in innovations in disease prevention and management that address the huge unmet health needs of aging populations.

Keywords: Aged;; Aging physiology;; Biological markers;; Chronic disease;; Delivery of health care;; Frail elderly;; Gait;; Geriatric assessment;; Health services for the aged;; Humans;; Inflammation;; Personalized medicine;; Prognosis;; Risk assessment;; Risk factors;; Treatment outcome.

Figures

Fig. 1
Fig. 1
Model of Disease Development. Environmental exposure plus host’s susceptibility (baseline risk) initiates the disease development process, which progresses from the preclinical to the clinical stage and ultimately the irreversible stage [102]. However, as organisms age, an increasing number of host factors could potentially interact the process at any stage, leading to unforeseen heterogeneity in the disease development that could not be explained by this model.
Fig. 2 –
Fig. 2 –
Central roles of biomarkers in personalized medicine. Biomarkers that indicate the activities of diseases pathogenesis at each stage could enhance baseline risk assessment, tracking of preclinical and clinical progression, prediction of health outcomes, therapeutic response or toxicity, thereby enabling personalized disease screening, prevention, diagnosis, prognosis assignment, and therapeutic decisions. Different biomarkers may play distinct roles.
Fig. 3
Fig. 3
A hierarchical aging model. Cellular abnormalities, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication, lead to dysfunction of physiological systems, which, once reaching a threshold, causes organism-level dysfunction characterized by an increased risk of failure (e.g. death and disability).

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