Identification of serum sirtuins as novel noninvasive protein markers for frailty

Frailty has emerged as a major health issue among older patients. A consensus on definition and diagnosis is yet to be achieved. Various biochemical abnormalities have been reported in frailty. Activation of sirtuins, a conserved family of NAD-dependent proteins, is one of the many mimics of calorie restriction which improves lifespan and health in experimental animals. In this cross-sectional study, we assessed the circulating sirtuin levels in 119 (59.5%) nonfrail and 81 (40.5%) frail individuals, diagnosed by Fried's criteria. Serum SIRT1, SIRT2, and SIRT3 were estimated by surface plasmon resonance (SPR) and Western blot. Serum sirtuins level in mean+SD; SIRT1 (nonfrail -4.67 +/- 0.48ng/L; frail - 3.72 +/- 0.48ng/L; P<0.0001), SIRT2 (nonfrail - 15.18 +/- 2.94ng/L; frail - 14.19 +/- 2.66ng/L; P=0.016), and SIRT3 (nonfrail-7.72 +/- 1.84ng/L; frail - 6.12 +/- 0.97ng/L; P<0.0001) levels were significantly lower among frail patients compared with the nonfrail. In multivariable regression analysis, lower sirtuins level were significantly associated with frailty after adjusting age, gender, diabetes mellitus, hypertension, cognitive status (Mini Mental State Examination scores) and number of comorbidities. For detecting the optimum diagnostic cutoff value a ROC analysis was carried out. The area under curve for SIRT1 was 0.9037 (cutoff - 4.29ng/L; sensitivity - 81.48%; specificity - 79.83%) and SIRT3 was 0.7988 (cutoff - 6.61ng/L; sensitivity - 70.37%; specificity - 70.59%). This study shows that lower circulating SIRT1 and SIRT3 levels can be distinctive marker of frailty.