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Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease.

Liu JC, Leung JM, Ngan DA, Nashta NF, Guillemi S, Harris M, Lima VD, Um SJ, Li Y, Tam S, Shaipanich T, Raju R, Hague C, Leipsic JA, Bourbeau J, Tan WC, Harrigan PR, Sin DD, Montaner J, Man SF - PLoS ONE (2015)

Bottom Line: Multivariable regression models identified factors associated with shortened aTL.Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049).HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.

View Article: PubMed Central - PubMed

Affiliation: Centre for Heart Lung Innovation, Vancouver, BC, Canada.

ABSTRACT
Combination antiretroviral therapy (cART) has extended the longevity of human immunodeficiency virus (HIV)-infected individuals. However, this has resulted in greater awareness of age-associated diseases such as chronic obstructive pulmonary disease (COPD). Accelerated cellular senescence may be responsible, but its magnitude as measured by leukocyte telomere length is unknown and its relationship to HIV-associated COPD has not yet been established. We measured absolute telomere length (aTL) in peripheral leukocytes from 231 HIV-infected adults. Comparisons were made to 691 HIV-uninfected individuals from a population-based sample. Subject quartiles of aTL were assessed for relationships with measures of HIV disease severity, airflow obstruction, and emphysema severity on computed tomographic (CT) imaging. Multivariable regression models identified factors associated with shortened aTL. Compared to HIV-uninfected subjects, the mean aTL in HIV-infected patients was markedly shorter by 27 kbp/genome (p<0.001); however, the slopes of aTL vs. age were not different (p=0.469). Patients with longer known durations of HIV infection (p=0.019) and lower nadir CD4 cell counts (p=0.023) had shorter aTL. Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049). HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.

No MeSH data available.


Related in: MedlinePlus

Absolute leukocyte telomere length by age for HIV-infected and non-HIV-infected individuals.When HIV-infected individuals (blue) are compared to non-HIV-infected individuals (red) from the CanCOLD cohort, significant differences in telomere length are seen. The respective slopes of aTL vs. age do not differ significantly between CanCOLD and HIV populations (p = 0.469). Solid lines represent the regression line; shaded areas represent the 95% confidence interval; the analysis has been adjusted for sex, BMI, smoking history and FEV1%Pred.
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pone.0124426.g002: Absolute leukocyte telomere length by age for HIV-infected and non-HIV-infected individuals.When HIV-infected individuals (blue) are compared to non-HIV-infected individuals (red) from the CanCOLD cohort, significant differences in telomere length are seen. The respective slopes of aTL vs. age do not differ significantly between CanCOLD and HIV populations (p = 0.469). Solid lines represent the regression line; shaded areas represent the 95% confidence interval; the analysis has been adjusted for sex, BMI, smoking history and FEV1%Pred.

Mentions: Additionally, aTL were measured in 691 HIV-uninfected individuals from the CanCOLD cohort (see Table 2 for demographic information). After adjusting for sex, BMI, smoking, and FEV1%Pred, there was a significant negative correlation between telomere length and age, in both the CanCOLD and HIV groups (R2 = 0.04, p<0.001 and R2 = 0.09, p = 0.030, respectively) (Fig 2). The slopes of aTL vs. age were similar between the two groups (p = 0.469) with both groups sharing a common slope of -0.713±0.155 kbp/genome/year (p<0.001). The difference in mean aTL between the CanCOLD and HIV populations (after adjustment for age, gender, BMI, smoking pack-years, and FEV1%Pred) is shown in Fig 3. The mean±SEM aTL for the CanCOLD and HIV populations were 150±3 and 123±4 kbp/genome, respectively (p<0.0001).


Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease.

Liu JC, Leung JM, Ngan DA, Nashta NF, Guillemi S, Harris M, Lima VD, Um SJ, Li Y, Tam S, Shaipanich T, Raju R, Hague C, Leipsic JA, Bourbeau J, Tan WC, Harrigan PR, Sin DD, Montaner J, Man SF - PLoS ONE (2015)

Absolute leukocyte telomere length by age for HIV-infected and non-HIV-infected individuals.When HIV-infected individuals (blue) are compared to non-HIV-infected individuals (red) from the CanCOLD cohort, significant differences in telomere length are seen. The respective slopes of aTL vs. age do not differ significantly between CanCOLD and HIV populations (p = 0.469). Solid lines represent the regression line; shaded areas represent the 95% confidence interval; the analysis has been adjusted for sex, BMI, smoking history and FEV1%Pred.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401786&req=5

pone.0124426.g002: Absolute leukocyte telomere length by age for HIV-infected and non-HIV-infected individuals.When HIV-infected individuals (blue) are compared to non-HIV-infected individuals (red) from the CanCOLD cohort, significant differences in telomere length are seen. The respective slopes of aTL vs. age do not differ significantly between CanCOLD and HIV populations (p = 0.469). Solid lines represent the regression line; shaded areas represent the 95% confidence interval; the analysis has been adjusted for sex, BMI, smoking history and FEV1%Pred.
Mentions: Additionally, aTL were measured in 691 HIV-uninfected individuals from the CanCOLD cohort (see Table 2 for demographic information). After adjusting for sex, BMI, smoking, and FEV1%Pred, there was a significant negative correlation between telomere length and age, in both the CanCOLD and HIV groups (R2 = 0.04, p<0.001 and R2 = 0.09, p = 0.030, respectively) (Fig 2). The slopes of aTL vs. age were similar between the two groups (p = 0.469) with both groups sharing a common slope of -0.713±0.155 kbp/genome/year (p<0.001). The difference in mean aTL between the CanCOLD and HIV populations (after adjustment for age, gender, BMI, smoking pack-years, and FEV1%Pred) is shown in Fig 3. The mean±SEM aTL for the CanCOLD and HIV populations were 150±3 and 123±4 kbp/genome, respectively (p<0.0001).

Bottom Line: Multivariable regression models identified factors associated with shortened aTL.Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049).HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.

View Article: PubMed Central - PubMed

Affiliation: Centre for Heart Lung Innovation, Vancouver, BC, Canada.

ABSTRACT
Combination antiretroviral therapy (cART) has extended the longevity of human immunodeficiency virus (HIV)-infected individuals. However, this has resulted in greater awareness of age-associated diseases such as chronic obstructive pulmonary disease (COPD). Accelerated cellular senescence may be responsible, but its magnitude as measured by leukocyte telomere length is unknown and its relationship to HIV-associated COPD has not yet been established. We measured absolute telomere length (aTL) in peripheral leukocytes from 231 HIV-infected adults. Comparisons were made to 691 HIV-uninfected individuals from a population-based sample. Subject quartiles of aTL were assessed for relationships with measures of HIV disease severity, airflow obstruction, and emphysema severity on computed tomographic (CT) imaging. Multivariable regression models identified factors associated with shortened aTL. Compared to HIV-uninfected subjects, the mean aTL in HIV-infected patients was markedly shorter by 27 kbp/genome (p<0.001); however, the slopes of aTL vs. age were not different (p=0.469). Patients with longer known durations of HIV infection (p=0.019) and lower nadir CD4 cell counts (p=0.023) had shorter aTL. Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049). HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.

No MeSH data available.


Related in: MedlinePlus