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
OAI Identifier:
oai:bonga.unisimon.edu.co:20.500.12442/1808
Acceso en línea:
http://hdl.handle.net/20.500.12442/1808
Palabra clave:
Lamin A
Aging
Frailty
COP cells
Circulating osteoprogenitors
Flow cytometry
Rights
License
Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional
Description
Summary: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.