Identification of potential protein biomarkers in sera of the elderly and their association with frailty status / Puvanesswaray Ramakrishnan
Early identification of frailty is of increasing importance as it may reduce the risk of adverse outcomes in older people. Potential biomarkers of frailty may be detected using proteomic applications that analyse serum samples of older subjects who are stratified according to their frailty status...
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| Format: | Thesis |
| Published: |
2018
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| Online Access: | http://studentsrepo.um.edu.my/11463/4/puva.pdf http://studentsrepo.um.edu.my/11463/ |
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| Summary: | Early identification of frailty is of increasing importance as it may reduce the risk of
adverse outcomes in older people. Potential biomarkers of frailty may be detected using
proteomic applications that analyse serum samples of older subjects who are stratified
according to their frailty status. This study is aimed at identifying potential biomarkers
of frailty associated with non-frail, pre-frail and frail status in older subjects. Frailty
status was determined using the Frailty Index. Blood samples taken from participants
recruited from University Malaya Medical Centre were analysed using proteomic
techniques. Enhanced expression of alpha-1-antitrypsin (A1AT), alpha-1B-glycoprotein
(A1BG), haptoglobin (HAP), hemopexin (HPX), kininogen (KNG1) and leucine-rich
alpha-2-glycoprotein (LRG) and reduced expression of apolipoprotein E (APOE) and
isoform 2 of clusterin (CLU) were detected in sera of frail elderly when samples were
subjected to 2-Dimensional Electrophoresis (2-DE) and analysed by densitometry. In
the pre-frail elderly, KNG and A1AT showed increased in abundance levels. In
glycoprotein analysis utilising CGB-lectin affinity blotting, LRG levels were
significantly reduced in pre-frail subjects while HAP levels were significantly higher in
the frail elderly relative to control non-frail subjects when pooled serum samples were
subjected to CMB-AP conjugated lectin in western blot analysis. Enzyme-linked
immunosorbent assay analysis showed serum A1AT concentration levels that were
significantly higher (degree of fold change <1.5) while APOE was reduced in frail older
adults compared with the non-frail, consistent with proteomic findings. This study
suggests an association between frailty and certain proteins with their levels identified
at different frailty status. The identification of these potential biomarkers of frailty may
iv
provides towards an understanding of frailty and identifies proteins which may
contribute towards the early detection of frailty in older people. |
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