Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study

Lamin A is a protein of the nuclear lamina. Low levels of lamin A expression are associated with osteosarcopenia in mice. In this study, we hypothesized that low lamin A expression is also associated with frailty in humans. We aimed to develop a non-invasive method to quantify lamin A expression in...

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Autores:: Al Saedi⁠, Ahmed
Gunawardene, Piumali
Bermeo, Sandra
Vogrin, Sara
Boersma, Derek
Phu, Steven
Singh⁠, Lakshman
Suriyaarachchi, Pushpa
Duque, Gustavo

Tipo de recurso:

Fecha de publicación:: 2018

Institución:: Universidad Simón Bolívar

Repositorio:: Repositorio Digital USB

Idioma:: eng

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dc.title.eng.fl_str_mv	Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study
title	Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study
spellingShingle	Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study Lamin A Aging Frailty COP cells Circulating osteoprogenitors Flow cytometry
title_short	Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study
title_full	Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study
title_fullStr	Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study
title_full_unstemmed	Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study
title_sort	Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study
dc.creator.fl_str_mv	Al Saedi⁠, Ahmed Gunawardene, Piumali Bermeo, Sandra Vogrin, Sara Boersma, Derek Phu, Steven Singh⁠, Lakshman Suriyaarachchi, Pushpa Duque, Gustavo
dc.contributor.author.none.fl_str_mv	Al Saedi⁠, Ahmed Gunawardene, Piumali Bermeo, Sandra Vogrin, Sara Boersma, Derek Phu, Steven Singh⁠, Lakshman Suriyaarachchi, Pushpa Duque, Gustavo
dc.subject.eng.fl_str_mv	Lamin A Aging Frailty COP cells Circulating osteoprogenitors Flow cytometry
topic	Lamin A Aging Frailty COP cells Circulating osteoprogenitors Flow cytometry
description	Lamin A is a protein of the nuclear lamina. Low levels of lamin A expression are associated with osteosarcopenia in mice. In this study, we hypothesized that low lamin A expression is also associated with frailty in humans. We aimed to develop a non-invasive method to quantify lamin A expression in epithelial and circulating osteoprogenitor (COP) cells, and to determine the relationship between lamin A expression and frailty in older individuals. COP cells and buccal swabs were obtained from 66 subjects (median age 74; 60% female; 26 non-frail, 23 pre-frail, and 17 frail) participating at the Nepean Osteoporosis and Frailty (NOF) Study. We quantified physical performance and disability, and stratified frailty in this population. Lamin A expression in epithelial and COP cells was quantified by flow cytometry. Linear regression models estimated the relationship between lamin A expression in buccal and COP cells, and prevalent disability and frailty. Lamin A expression in buccal cells showed no association with either disability or frailty. Low lamin A expression values in COP cells were associated with frailty. Frail individuals showed 60% lower levels of lamin A compared to non-frail (95% CI − 36 to − 74%, p < 0.001) and 62% lower levels compared to pre-frail (95%CI − 40 to − 76%, p < 0.001). In summary, we have identified lamin A expression in COP cells as a strong indicator of frailty. Further work is needed to understand lamin A expression as a risk stratifier, biomarker, or therapeutic target in frail older persons.
publishDate	2018
dc.date.accessioned.none.fl_str_mv	2018-03-07T22:37:28Z
dc.date.available.none.fl_str_mv	2018-03-07T22:37:28Z
dc.date.issued.none.fl_str_mv	2018-02
dc.type.spa.fl_str_mv	article
dc.type.coar.fl_str_mv	http://purl.org/coar/resource_type/c_6501
dc.identifier.issn.none.fl_str_mv	05315565
dc.identifier.uri.none.fl_str_mv	http://hdl.handle.net/20.500.12442/1808
identifier_str_mv	05315565
url	http://hdl.handle.net/20.500.12442/1808
dc.language.iso.spa.fl_str_mv	eng
language	eng
dc.rights.coar.fl_str_mv	http://purl.org/coar/access_right/c_abf2
dc.rights.license.spa.fl_str_mv	Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional
rights_invalid_str_mv	Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional http://purl.org/coar/access_right/c_abf2
dc.publisher.eng.fl_str_mv	Elsevier
dc.source.eng.fl_str_mv	Experimental Gerontology Vol. 102 (2018)
institution	Universidad Simón Bolívar
dc.source.uri.none.fl_str_mv	https://www.sciencedirect.com/science/article/pii/S0531556517307428?via%3Dihub
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repository.mail.fl_str_mv	bibliotecas@biteca.com
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spelling	Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacionalhttp://purl.org/coar/access_right/c_abf2Al Saedi⁠, Ahmedf83ed6a8-7bc6-41be-92aa-bf9350104cf3-1Gunawardene, Piumali4f64fa86-c6d8-4ef5-b4fa-751fcccb8ea6-1Bermeo, Sandra5adcb3ad-0b9f-41f8-8a5f-a4d6086d31ef-1Vogrin, Sara806a44b8-9f2a-491f-b91b-5796665f7cbd-1Boersma, Derek5295ef81-cfd1-4b34-8a20-14c07ab4bab7-1Phu, Stevenc0787bef-53f4-43cd-8857-98d4634a6341-1Singh⁠, Lakshman4ff473d1-8cc5-4594-8db8-b6ccb19fad11-1Suriyaarachchi, Pushpade4aafc6-f489-4964-8864-fd332b5e5fa0-1Duque, Gustavof99ef41b-e311-4165-bbc4-73e084153d5f-12018-03-07T22:37:28Z2018-03-07T22:37:28Z2018-0205315565http://hdl.handle.net/20.500.12442/1808Lamin A is a protein of the nuclear lamina. Low levels of lamin A expression are associated with osteosarcopenia in mice. In this study, we hypothesized that low lamin A expression is also associated with frailty in humans. We aimed to develop a non-invasive method to quantify lamin A expression in epithelial and circulating osteoprogenitor (COP) cells, and to determine the relationship between lamin A expression and frailty in older individuals. COP cells and buccal swabs were obtained from 66 subjects (median age 74; 60% female; 26 non-frail, 23 pre-frail, and 17 frail) participating at the Nepean Osteoporosis and Frailty (NOF) Study. We quantified physical performance and disability, and stratified frailty in this population. Lamin A expression in epithelial and COP cells was quantified by flow cytometry. Linear regression models estimated the relationship between lamin A expression in buccal and COP cells, and prevalent disability and frailty. Lamin A expression in buccal cells showed no association with either disability or frailty. Low lamin A expression values in COP cells were associated with frailty. Frail individuals showed 60% lower levels of lamin A compared to non-frail (95% CI − 36 to − 74%, p < 0.001) and 62% lower levels compared to pre-frail (95%CI − 40 to − 76%, p < 0.001). In summary, we have identified lamin A expression in COP cells as a strong indicator of frailty. Further work is needed to understand lamin A expression as a risk stratifier, biomarker, or therapeutic target in frail older persons.engElsevierExperimental GerontologyVol. 102 (2018)https://www.sciencedirect.com/science/article/pii/S0531556517307428?via%3DihubLamin AAgingFrailtyCOP cellsCirculating osteoprogenitorsFlow cytometryLamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Studyarticlehttp://purl.org/coar/resource_type/c_6501Ahmed, N., Mandel, R., Fain, M.J., 2007. Frailty: an emerging geriatric syndrome. Am. J. Med. 120, 748–753.Akter, R., Rivas, D., Geneau, G., Drissi, H., Duque, G., 2009. 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Med. 27, 1–15.LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bonga.unisimon.edu.co/bitstreams/95962147-1846-4a62-8859-90302169920a/download8a4605be74aa9ea9d79846c1fba20a33MD5220.500.12442/1808oai:bonga.unisimon.edu.co:20.500.12442/18082019-04-11 21:51:42.056metadata.onlyhttps://bonga.unisimon.edu.coDSpace UniSimonbibliotecas@biteca.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

Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study

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