Abstract
Frailty is characterized by a decline in physiological reserve and increased vulnerability. Previous studies have shown that KLOTHO (KL) plays a protective role in several age-related diseases. We hypothesize a probable protective effect of KL on frailty in the elderly population and included a cohort of Chinese nonagenarians and centenarians for our study. This study is part of a cross-sectional study and secondary analysis of the Project of Longevity and Aging in Dujiangyan (PLAD) study, which was conducted in Southwest China. Community-dwelling Chinese residents aged 90 years or older were included in this study. Frailty was determined using the FRAIL scale as proposed by the International Association of Nutrition and Aging. On the FRAIL scale, frailty was defined by a score of ≥3. G-395A (rs1207568) genotyping of the promoter region of the KL gene was performed using TaqMan allelic discrimination assay. A total of 632 participants (68.4% females; mean age: 93.5 ± 3.2 years) were included. KL G-395A polymorphism genotype frequencies were 1.7% AA, 25.6% GA, and 72.7% GG in our sample. GG genotype frequencies for the frailty and control groups were 83.6% and 71.2%, respectively. Frailty prevalence was significantly lower in the GA+AA group when compared to the GG genotype group (6.9% vs. 13.3%, P = 0.026). In addition, subjects with a GA+AA genotype had a significantly lower risk of frailty (odds ratio (OR): 0.47, 95% confidence interval (CI) 0.23 to 0.97, P = 0.040) compared to the GG genotype after adjusting for age, gender, education level, smoking, alcohol consumption, exercise, body mass index (BMI), cognitive impairment, and other potential factors. KL-395A allele carrying genotypes (GA and AA) is associated with a lower risk of frailty relative to GG genotypes in a sample of Chinese nonagenarians and centenarians.
Highlights
Frailty is defined as the age-related state of increased vulnerability to poor resolution of homeostasis after a stressor event and is related to the decline of several physiological systems[1]
This study provided us with the opportunity to explore the relationship between the KL G-395A single nucleotide polymorphisms (SNPs) and frailty in this specific cohort
The mean Mini-Mental Status Examination (MMSE) score was significantly lower in the frailty group when compared to the control group (12.6 ± 6.2 vs. 15.3 ± 5.4, respectively, P < 0.001)
Summary
Frailty is defined as the age-related state of increased vulnerability to poor resolution of homeostasis after a stressor event and is related to the decline of several physiological systems[1]. Previous studies have shown that several factors are associated with frailty in the elderly, it is still challenging to find a single marker or gene to identify frailty[4,5,6,7,8,9]. In a longitudinal study, the additive genetic component accounts for 43% of the overall frailty phenotype variability robustness index ratio[10] This proportion was higher in males than in females and older subjects (mean age over 77.7 years of age)[10]. Over 10 mutations or single nucleotide polymorphisms (SNPs) were found in the human KL gene[13]. The KL gene is related with aging, chronic diseases, and disorders of several physiological systems, all of which are closely related with frailty in the elderly. This study provided us with the opportunity to explore the relationship between the KL G-395A SNP and frailty in this specific cohort
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