Identification of serum sirtuins as novel noninvasive protein markers for frailty

Abstract

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 ± 0.48 ng/μL; frail – 3.72 ± 0.48 ng/μL; P < 0.0001), SIRT2 (nonfrail – 15.18 ± 2.94 ng/μL; frail – 14.19 ± 2.66 ng/μL; P = 0.016), and SIRT3 (nonfrail-7.72 ± 1.84 ng/μL; frail – 6.12 ± 0.97 ng/μL; 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 – 4.29 ng/μL; sensitivity – 81.48%; specificity – 79.83%) and SIRT3 was 0.7988 (cutoff – 6.61 ng/μL; sensitivity – 70.37%; specificity – 70.59%). This study shows that lower circulating SIRT1 and SIRT3 levels can be distinctive marker of frailty.

Shared biological pathways for frailty and cognitive impairment: A systematic review

“…Two markers measured by serum/plasma were associated with both cognitive impairment and frailty, these included: sirtuin 1 and cystatin C. The down regulation of Sirtuin 1 has been reported to be involved in the pathway that controls the expression of Apeta peptide through ADAM10 (Kumar et al, 2013). Concentrations of sirtuin 1 decline with age but the decline was found to be more significant in individuals with cognitive impairment and frailty compared to age matched healthy individuals (Kumar et al, 2013, 2014). Additionally, cystatin C has been thought to bind to soluble Apeta preventing accumulation in the brain (Sundelof et al, 2008).…”

Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults

“…Dysregulation of the sirtuin system could favor the development of frailty-related diseases such as type 2 diabetes (Kitada and Koya, 2013), cardiovascular diseases (Cencioni et al, 2015) and pulmonary diseases (Conti et al, 2015). Furthermore, the relationship between sirtuins and frailty is supported by the association of this condition with reduced circulating levels of sirtuins, being serum concentrations SIRT1 and SIRT3 proposed as diagnostic tools for frailty (Kumar et al, 2014). The pathophysiological role of sirtuins deficiency in frailty could be related to the importance of these factors in skeletal muscle health (Tonkin et al, 2012).…”

Expression of cellular protective proteins SIRT1, HSP70 and SOD2 correlates with age and is significantly higher in NK cells of the oldest seniors

“…In humans levels of SIRT1, SIRT2 and SIRT3 were analyzed in sera of both frail and non-frail seniors and the lower circulating SIRT1 and SIRT3 levels were found to be a distinguishing marker of frailty [29]. …”