Association between leukocyte telomere length and sex by quantile regression analysis

Abstract

Introduction: Telomere length (TL) is a biomarker of cellular proliferative history. In healthy individuals, leukocyte TL shortens with age and associates with the lifespan of men and women. However, most of studies had used linear regression models to address the association of the TL attrition, aging and sex.

Methods: We evaluated the association between the TL, aging and sex in a cohort of 180 healthy subjects by quantile regression. The TL of nucleated blood cells was measured by fluorescent in situ hypridization (flow-FISH) in a cohort of 89 men, 81 women, and 10 umbilical cord samples. The results were validated by quantitative polymerase chain reaction (qPCR) and compared to a linear regression analysis.

Results: By quantile regression, telomere dynamics slightly differed between sexes with aging: women had longer telomeres at birth and slower attrition rate than men until the sixth decade of life; after that, TL eroded faster and became shorter than that in men. These differences were not observed by linear regression analysis, as the overall telomere attrition rates in women and men were similar (42 pb per year, p < 0.0001 vs. 45 pb kb per year, p < 0.0001). Also, qPCR did not recapitulate flow-FISH findings, as the telomere dynamics by qPCR followed a linear model.

Conclusion: The quantile regression analysis accurately reproduced a third-order polynomial TL attrition rate in both women and men, but it depended on the technique applied to measure TL. The Flow-FISH reproduced the expected telomere dynamics through life and, differently from the qPCR, was able to detect the subtle TL variations associated with sex and aging.

Keywords: Flow-fish; Quantile regression; Sex; Telomere length.

Fig. 1

Dynamics of telomere length in women and men described by quantile regression analysis. Telomere length as a marker of aging in the white blood cells of healthy individuals ranging from zero (umbilical cord samples) to 92 years old (n = 180). The vertical axis represents the telomere length in kilobases and the horizontal axis, the age in years. The 1st, 50th (median) and 99th percentiles were adjusted to the data and are shown in the graphics. (A) The relationship between telomere length and age followed a third order polynomial model, described by the equation Yp = a + bx + cx + dx, shown in the graphic. The independent variable x is the age, Yp is the 50th percentile of the dependent variable telomere length (kb) and a, b, c and d are parameters estimated by the quantile regression. (B) The adjustment of the 1st, 50th (median) and 99th percentiles to the data was performed by the quantile regression. The telomere dynamics through life in (C) women (n = 81) and (D) men (n = 89).

Fig. 2

Telomere length (TL) dynamics of according to aging in women (red curve) and men (blue curve) by flow-FISH and qPCR. The comparison of the TL medians (50th percentiles) according to sex. (A) The TL was measured in the white blood cells of 180 healthy individuals, ranging in age from zero (umbilical cord samples) to 92 years old, by the flow-FISH. Women appeared to have longer telomeres and a slower rate of attrition than men. From the fifties on, the telomere length in women decreased rapidly, remaining lower than that of men after the eighties. (B) The TL was measured in white blood cells of 241 healthy individuals, ranging in age from zero (umbilical cord samples) to 88 years old, by the qPCR. No differences in the TL or telomere dynamics was seen between women and men.