Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study
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Fecha
2018-02
Autores
Al Saedi, Ahmed
Gunawardene, Piumali
Bermeo, Sandra
Vogrin, Sara
Boersma, Derek
Phu, Steven
Singh, Lakshman
Suriyaarachchi, Pushpa
Duque, Gustavo
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Editor
Elsevier
Resumen
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.
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Palabras clave
Lamin A, Aging, Frailty, COP cells, Circulating osteoprogenitors, Flow cytometry