Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease
Female; Humans; Male; Cohort Studies; Adult; Middle Aged; HIV Infections; Pulmonary Disease; Leukocytes; Chronic Obstructive; Cell Aging; Telomere
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.
2015
Liu JCY; Leung JM; Ngan DA; Nashta NF; Guillemi S; Harris M; Lima VD; Um Soo-Jung; Li Y; Tam S; Shaipanich T; Raju Rekha; Hague C; Leipsic JA; Bourbeau J; Tan Wan C; Harrigan PR; Sin Don D; Montaner J; Man SFP
Plos One
2015
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1371/journal.pone.0124426" target="_blank" rel="noreferrer">10.1371/journal.pone.0124426</a>
Accelerated telomere shortening in response to life stress
Female; Humans; Adult; Middle Aged; Age Factors; Non-U.S. Gov't; P.H.S.; Research Support; U.S. Gov't; Psychological; Stress; Leukocytes; mothers; Telemeres; Cell Aging; Mononuclear/physiology; Oxidative Stress; Premenopause; Telomere/metabolism/ultrastructure
Numerous studies demonstrate links between chronic stress and indices of poor health, including risk factors for cardiovascular disease and poorer immune function. Nevertheless, the exact mechanisms of how stress gets "under the skin" remain elusive. We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress--both perceived stress and chronicity of stress--is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women. These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases.
2004
Epel ES; Blackburn EH; Lin J; Dhabhar FS; Adler NE; Morrow JD; Cawthon RM
Proceedings Of The National Academy Of Sciences Of The United States Of America
2004
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1073/pnas.0407162101" target="_blank" rel="noreferrer">10.1073/pnas.0407162101</a>