1.
Biological Processes and Biomarkers Related to Frailty in Older Adults: A State-of-the-Science Literature Review.
Wang, J, Maxwell, CA, Yu, F
Biological research for nursing. 2019;(1):80-106
Abstract
The objectives of this literature review were to (1) synthesize biological processes linked to frailty and their corresponding biomarkers and (2) identify potential associations among these processes and biomarkers. In September 2016, PubMed, Cumulative Index to Nursing and Allied Health, Cochrane Library, and Embase were searched. Studies examining biological processes related to frailty in older adults (≥60 years) were included. Studies were excluded if they did not employ specific measures of frailty, did not report the association between biomarkers and frailty, or focused on nonelderly samples (average age < 60). Review articles, commentaries, editorials, and non-English articles were also excluded. Fifty-two articles were reviewed, reporting six biological processes related to frailty and multiple associated biomarkers. The processes (biomarkers) include brain changes (neurotrophic factor, gray matter volume), endocrine dysregulation (growth hormones [insulin-like growth factor-1 and binding proteins], hormones related to glucose and insulin, the vitamin D axis, thyroid function, reproductive axis, and hypothalamic-pituitary-adrenal axis), enhanced inflammation (C-reactive protein, interleukin-6), immune dysfunction (neutrophils, monocytes, neopterin, CD8+CD28-T cells, albumin), metabolic imbalance (micronutrients, metabolites, enzyme-activity indices, metabolic end products), and oxidative stress (antioxidants, telomere length, glutathione/oxidized glutathione ratio). Bidirectional interrelationships exist within and between these processes. Biomarkers were associated with frailty in varied strengths, and the causality remains unclear. In conclusion, frailty is related to multisystem physiological changes. Future research should examine the dynamic interactions among these processes to inform causality of frailty. Given the multifactorial nature of frailty, a composite index of multisystem biomarkers would likely be more informative than single biomarkers in early detection of frailty.
2.
Effect of Alfacalcidol on Inflammatory markers and T Cell Subsets in Elderly with Frailty Syndrome: a Double Blind Randomized Controlled Trial.
Rizka, A, Setiati, S, Harimurti, K, Sadikin, M, Mansur, IG
Acta medica Indonesiana. 2018;(3):215-221
Abstract
BACKGROUND Alphacalcidol, a vitamin D analog, shows immune regulatory potency as it works on the macrophage and T cell to control inflammation and T cell dysregulation in elderly. None has been known about its effect on elderly with various states of frailty syndrome, which have different level of chronic low grade inflammation. This study aimed to determine the effect of alphacalcidol on inflammatory cytokines (IL-6, IL-10, g-IFN ) and T cell subsets (CD4/CD8 ratio and CD8+ CD28-) of elderly with various stages of frailty syndrome. METHODS from January to July 2017, a double blind randomized controlled trial (RCT) with allocation concealment, involving 110 elderly subjects from Geriatric Outpatient Clinic Cipto Mangunkusumo Hospital Jakarta, was conducted to measure the effect of 0.5 mcg alphacalcidol administration for 90 days to inflammatory cytokines (IL-6, IL-10, g-IFN) from PBMC culture supernatant, as well as CD4/CD8 and CD8+CD28- percentage using flow cytometry. Statistical analysis using SPSS version 20 was performed with t-test to measure mean difference. RESULTS of 110 subjects involved in the RCT consisting of 27 fit, 27 pre-frail and 56 frail elderly, 25(OH)D serum level was found to be as low as 25.59 (12.2) ng/ml in alphacalcidol group and 28.27 (10.4) ng/ml in placebo group. Alphacalcidol did not decrease IL-6 (p=0.4) and g- IFN (p=0.001), but it increased IL-10 (p=0,005) and decreased IL6/IL10 ratio (p=0.008). Alphacalcidol increased CD4/CD8 ratio from 2.68 (SD 2.45) to 3.2 (SD 2.9); p=0.001 and decreased CD8+ CD28- percentage from 5.1 (SD 3.96) to 2.5 (1.5); p<0.001. Sub group analysis showed similar patterns in all frailty states. CONCLUSION Alphacalcidol improves immune senescence by acting as anti-inflammatory agent through increased IL-10 and decreased IL6/IL-10 ratio and also improves cellular immunity through increased CD4/CD8 ratio and decreased CD8+ CD28- subset in elderly. This effect is not influenced by frailty state.