Identification of serum sirtuins as novel noninvasive protein markers for frailty

Summary 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...

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Published in:Aging cell 2014-12, Vol.13 (6), p.975-980
Main Authors: Kumar, Rahul, Mohan, Navinath, Upadhyay, Ashish Datt, Singh, Amrendra Pratap, Sahu, Vishal, Dwivedi, Sadanand, Dey, Aparajit B., Dey, Sharmistha
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Language:English
Subjects:
Aged
Aged, 80 and over
Analysis
biomarker
Biomarkers - blood
Comorbidity
Diabetes
Diagnosis
Female
Frail Elderly
frailty
Health aspects
Humans
Hypertension
Male
Original
Proteins
serum
sirtuin
Sirtuins - blood
Surface Plasmon Resonance
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cited_by cdi_FETCH-LOGICAL-c5850-a026d20c22469394dc8c634bb196293e7267ad211eea7e2a6ae85730730381193
cites cdi_FETCH-LOGICAL-c5850-a026d20c22469394dc8c634bb196293e7267ad211eea7e2a6ae85730730381193
container_end_page 980
container_issue 6
container_start_page 975
container_title Aging cell
container_volume 13
creator Kumar, Rahul
Mohan, Navinath
Upadhyay, Ashish Datt
Singh, Amrendra Pratap
Sahu, Vishal
Dwivedi, Sadanand
Dey, Aparajit B.
Dey, Sharmistha
description Summary 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 
doi_str_mv 10.1111/acel.12260
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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 &lt; 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 &lt; 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.</description><identifier>ISSN: 1474-9718</identifier><identifier>EISSN: 1474-9726</identifier><identifier>DOI: 10.1111/acel.12260</identifier><identifier>PMID: 25100619</identifier><language>eng</language><publisher>England: John Wiley &amp; Sons, Inc</publisher><subject>Aged ; Aged, 80 and over ; Analysis ; biomarker ; Biomarkers - blood ; Comorbidity ; Diabetes ; Diagnosis ; Female ; Frail Elderly ; frailty ; Health aspects ; Humans ; Hypertension ; Male ; Original ; Proteins ; serum ; sirtuin ; Sirtuins - blood ; Surface Plasmon Resonance</subject><ispartof>Aging cell, 2014-12, Vol.13 (6), p.975-980</ispartof><rights>2014 The Authors. published by the Anatomical Society and John Wiley &amp; Sons Ltd.</rights><rights>2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley &amp; Sons Ltd.</rights><rights>COPYRIGHT 2014 John Wiley &amp; Sons, Inc.</rights><rights>Copyright © 2014 The Anatomical Society and John Wiley &amp; Sons Ltd</rights><rights>2014 The Authors. published by the Anatomical Society and John Wiley &amp; Sons Ltd. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5850-a026d20c22469394dc8c634bb196293e7267ad211eea7e2a6ae85730730381193</citedby><cites>FETCH-LOGICAL-c5850-a026d20c22469394dc8c634bb196293e7267ad211eea7e2a6ae85730730381193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326933/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1627002778?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,11543,25734,27905,27906,36993,36994,44571,46033,46457,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25100619$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kumar, Rahul</creatorcontrib><creatorcontrib>Mohan, Navinath</creatorcontrib><creatorcontrib>Upadhyay, Ashish Datt</creatorcontrib><creatorcontrib>Singh, Amrendra Pratap</creatorcontrib><creatorcontrib>Sahu, Vishal</creatorcontrib><creatorcontrib>Dwivedi, Sadanand</creatorcontrib><creatorcontrib>Dey, Aparajit B.</creatorcontrib><creatorcontrib>Dey, Sharmistha</creatorcontrib><title>Identification of serum sirtuins as novel noninvasive protein markers for frailty</title><title>Aging cell</title><addtitle>Aging Cell</addtitle><description>Summary 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 &lt; 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 &lt; 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%). 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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 &lt; 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 &lt; 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.</abstract><cop>England</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>25100619</pmid><doi>10.1111/acel.12260</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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source Wiley Online Library; Publicly Available Content Database; PubMed Central
subjects Aged
Aged, 80 and over
Analysis
biomarker
Biomarkers - blood
Comorbidity
Diabetes
Diagnosis
Female
Frail Elderly
frailty
Health aspects
Humans
Hypertension
Male
Original
Proteins
serum
sirtuin
Sirtuins - blood
Surface Plasmon Resonance
title Identification of serum sirtuins as novel noninvasive protein markers for frailty
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