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Aging and disease    2018, Vol. 9 Issue (6) : 1010-1019     DOI: 10.14336/AD.2018.0204
Orginal Article |
Stronger Association between Insomnia Symptoms and Shorter Telomere Length in Old HIV-Infected Patients Compared with Uninfected Individuals
Ding Yingying1,2, Lin Haijiang3, Zhou Sujuan1,2, Wang Keran1,2, Li Lingling1,2, Zhang Yucheng1,2, Yao Yuan1,2, Gao Meiyang1,2, Liu Xing1,2, He Na1,2,*
1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
2The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
3Taizhou City Center for Disease Control and Prevention, Taizhou City, Zhejiang, China
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Abstract  

Growing evidence suggests that HIV infection may accelerate biological aging. Insomnia symptoms, particularly in later life, exacerbate cellular aging. We examined the association between insomnia symptoms and leukocyte telomere length (LTL), and further explored how this association was affected by HIV serostatus and age. Data were assessed from 244 HIV-infected individuals ≥40 years and 244 HIV-uninfected individuals who were frequency-matched by age, gender and education level. Insomnia symptoms were assessed by responses to four sleep-related questions covering the past month. We performed multivariable linear regression with logarithmically transformed LTL and reported exponentiated coefficients. HIV-infected individuals had shorter LTL compared to uninfected individuals (geometric mean 0.82 vs 0.89, P=0.052), and this association remained after adjustment for gender, education level, and smoking history (-7.4%, P=0.051) but markedly attenuated after additional adjustment for insomnia and depressive symptoms (-3.7%, P=0.367). Significant interactions between age group (55-82 vs 40-54 years) and insomnia symptoms on LTL were observed in the HIV-infected individuals (-28.4%, P=0.033) but not the uninfected (-17.9%, P=0.250). After stratifying by age group, LTL was independently associated with insomnia symptoms in those 55 years and older among the HIV-infected individuals (-24.5%, P=0.026) but not those 40-54 years old (-9.8%, P=0.428). Our findings suggest that elevated insomnia and depressive symptoms may partly explain the correlation between HIV serostatus and shorter LTL. Significant association between insomnia and shorter LTL observed in elderly HIV-infected but not in uninfected individuals suggest that such adverse effect may begin at an earlier age or is more pronounced in HIV-infected individuals but requires further investigation.

Keywords HIV      older age      insomnia symptoms      telomere length     
Corresponding Authors: He Na   
About author:

These authors contributed equally to this work

Issue Date: 26 October 2017
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Ding Yingying
Lin Haijiang
Zhou Sujuan
Wang Keran
Li Lingling
Zhang Yucheng
Yao Yuan
Gao Meiyang
Liu Xing
He Na
Cite this article:   
Ding Yingying,Lin Haijiang,Zhou Sujuan, et al. Stronger Association between Insomnia Symptoms and Shorter Telomere Length in Old HIV-Infected Patients Compared with Uninfected Individuals[J]. Aging and disease, 2018, 9(6): 1010-1019.
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http://www.aginganddisease.org/EN/10.14336/AD.2018.0204     OR     http://www.aginganddisease.org/EN/Y2018/V9/I6/1010
CharacteristicsHIV-infected participantsHIV-uninfected participants

All40-54 years55-82 yearsPaAll40-54 years55-82 yearsPaPa
Subjects2441578724415787
Age, years52.4±9.046.7±36.563.0±6.3<.00152.5±9.146.7±3.762.9±6.0<.0010.933
Male180 (73.8)118 (75.2)62 (71.3)0.508180 (73.8)118 (75.2)62 (71.3)0.5081.000
Junior middle school or obove145 (59.4)115 (73.2)30 (34.5)<.001145 (59.4)115 (73.2)30 (34.5)<.0011.000
BMI, kg/m222.1
(20.3-24.0)
22.4
(20.6-24.3)
21.5
(19.9-23.1)
0.00223.7
(22.1-26.0)
24.2
(22.3-26.5)
23.4
(21.5-25.4)
0.028<.001
Waist circumference, cm81.0
(75.5-86.0)
81.0
(75.0-86.0)
81.0
(76.0-88.0)
0.11884.0
(78.0-90.0)
84.0
(78.0-89.0)
86.0
(80.0-91.0)
0.070<.001
Hip circumference, cm90.0
(84.7-96.0)
90.0
(85.5-96.0)
88.7
(84.0-95.0)
0.10495.0
(90.0-99.0)
96.0
(90.0-100.0)
94.0
(90.0-98.0)
0.249<.001
WHR above the cutoff154 (63.1)96 (61.1)58 (66.7)0.392133 (54.5)75 (47.8)58 (66.7)0.0040.053
Smoking history0.1190.1150.021
Current smoker70 (28.0)49 (31.2)21 (24.1)94 (37.6)58 (36.9)36 (41.4)
Previous smoker29 (11.6)14 (8.9)15 (17.2)16 (6.4)7 (4.5)9 (10.3)
Never smoked145 (59.4)94 (59.9)51 (58.6)134 (54.9)92 (58.6)42 (48.3)
Current alcohol user18 (7.4)11 (7.0)7 (8.0)0.76620 (8.3)9 (5.7)11 (12.6)0.0590.735
Depressive symptoms as a continuous variable16.6±4.816.5±4.916.6±4.70.90113.3±3.713.4±3.816.4±4.90.039<.001
Insomnia symptoms46 (18.9)28 (17.8)18 (20.7)0.58523 (9.4)12 (7.6)11 (12.6)0.2000.003
Insomnia symptoms as a continuous variable6.5±2.76.5±2.66.6±2.90.8945.8±2.25.5±1.96.4±2.50.0030.002
HIV-related parameters
Homosexual HIV transmission45 (18.4)36 (22.9)9 (10.3)0.015
Years since HIV diagnosis3.0
(1.6-4.7)
2.7
(1.5-4.6)
3.5
(2.0-4.7)
0.187
Nadir CD4 count, cells/μL0.394
< 10060 (24.5)43 (27.4)17 (19.5)
100-19987 (35.7)54 (34.4)33 (37.9)
≥ 20097 (39.7)60 (38.2)37 (42.5)
Current CD4 count ≥ 200 cells/μL205 (84.0)132 (84.1)79 (83.9)0.973
Using cART at enrollment0.277
cART naïve20 (8.2)16 (10.2)4 (4.6)
Duration on cART < 3 years133 (54.5)82 (52.2)51 (58.6)
Duration on cART ≥ 3 years91 (37.3)59 (37.6)32 (36.8)
Duration on cARTb, years2.4
(0.9-3.7)
2.0
(0.9-3.7)
2.6
(0.8-3.8)
0.544
Using EFV at enrollment127 (52.0)80 (51.0)47 (54.0)0.646
Plasma HIV RNA < 200 copies/mLc158 (90.3)102 (92.7)56 (86.1)0.156
Leukocyte telomere length (LTL)0.91±0.420.92±0.400.89±0.440.6570.96±0.400.97±0.390.94±0.410.5900.178
Geometric LTLd0.82 (0.77-0.87)0.83 (0.77-0.89)0.80 (0.72-0.88)0.5480.89 (0.84-0.93)0.90 (0.84-0.95)0.86 (0.79-0.94)0.4800.052
Table 1  Sample characteristics of HIV-infected and uninfected participants stratified by age group.
Percentage
change (95% CI)a
P
All HIV-infected participants
 Age group (55-82 vs 40-54 years)3.8 (-0.8 to 17.3)0.668
 Insomnia symptoms8.5 (-10.2 to 31.1)0.397
 Current CD4 count ≥ 200 cells/μL15.9 (-1.1 to 35.8)0.069
 Insomnia symptoms × age group interaction-28.4 (-2.8 to 47.2)0.033
HIV-infected participants aged 40-54 years
 Age as a continuous variable-8.0 (-9.8 to -6.1)0.412
 Insomnia symptoms9.7 (-10.0 to 31.5)0.397
 Current CD4 count ≥ 200 cells/μL20.0 (-1.7 to 46.6)0.076
HIV-infected participants aged 55-82 years
Model 1b
 Age as a continuous variable-1.2 (-2.9 to 0.4)0.108
 Insomnia symptoms-24.5 (-40.8 to -3.7)0.026
Model 2b
 Age as a continuous variable-0.9 (-2.5 to 0.7)0.267
 Depressive symptoms as a continuous variable-2.5 (-4.5 to -0.5)0.018
Table 2  Multivariable analyses of the association between various factors and leukocyte telomere length in HIV-infected participants according to age group.
Figure 1.  Geometric mean and 95% confidence interval of leukocyte telomere length in all HIV-infected and HIV-uninfected participants and according to age group. Punadj was calculated using t-test, Padj was calculated using multivariable linear regression model adjusting for age as continuous variable. Abbreviations: age-adj, age adjusted; CI, confidence interval; LTL, leukocyte telomere length; unadj, unadjusted.
Percentage
change (95% CI)a
P
All HIV-uninfected participants
 Age group (55-82 vs 40-54 years)-4.9 (-15.2 to 6.7)0.396
 Junior middle school or above-14.0 (-22.8 to -4.3)0.006
 Depressive symptoms as a continuous variable-2.5 (-3.8 to -1.2)<.001
 Insomnia symptoms8.4 (-13.9 to 36.5)0.492
 Insomnia symptoms × age group interaction-17.9 (-41.3 to 14.9)0.250
HIV-uninfected participants aged 40-54 years
 Age as a continuous variable-1.6 (3.3 to 0.1)0.064
 Depressive symptoms as a continuous variable-2.4 (-4.0 to -0.7)0.006
 Insomnia symptoms7.3 (-14.8 to 35.0)0.550
HIV-uninfected participants aged 55-82 years
Model 1b
 Age as a continuous variable-0.9 (-2.2 to 0.4)0.195
 Junior middle school or above-29.9 (-41.0 to -16.7)<.001
 WHR above the cutoff-20.7 (-33.6 to -5.3)0.012
 Insomnia symptoms-9.8 (-30.0 to 16.2)0.428
Model 2b
 Age as a continuous variable-0.7 (-2.0 to 0.7)0.314
 Junior middle school or above-27.9 (-39.4 to -14.3)<.001
 WHR above the cutoff-22.1 (-34.5 to -7.0)0.006
 Depressive symptoms as a continuous variable-2.0 (-4.2 to 0.3)0.090
Table 3  Multivariable analyses of the association between various factors and leukocyte telomere length in HIV-uninfected participants according to age group.
[1] Roth T (2007). Insomnia: definition, prevalence, etiology, and consequences. J Clin Sleep Med, 3: S7–10.
[2] Lallukka T, Podlipskytė A, Sivertsen B, Andruškienė J, Varoneckas G, Lahelma E, et al. (2016). Insomnia symptoms and mortality: a register-linked study among women and men from Finland, Norway and Lithuania. J Sleep Res, 25: 96–103.
[3] Javaheri S, Redline S (2017). Insomnia and risk of cardiovascular disease. Chest, 152: 435–44.
[4] Carroll JE, Carrillo C, Olmstead R, Witarama T, Breen EC, Yokomizo M, et al. (2015). Sleep deprivation and divergent toll-like receptor-4 activation of cellular inflammation in aging. Sleep, 38: 205–11.
[5] Carroll JE, Cole SW, Seeman TE, Breen EC, Witarama T, Arevalo JM, et al. (2016). Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans. Brain Behav Immun, 51: 223–9.
[6] Blackburn EH (1991). Telomeres. Trends Biochem Sci, 16: 378–81.
[7] Chen W, Kimura M, Kim S, Cao X, Srinivasan SR, Berenson GS, et al. (2011). Longitudinal versus cross-sectional evaluations of leukocyte telomere length dynamics: age-dependent telomere shortening is the rule. J Gerontol A Biol Sci Med Sci, 66:312–319.
[8] Bernadotte A, Mikhelson VM, Spivak IM (2016). Markers of cellular senescence. Telomere shortening as a marker of cellular senescence. Aging (Albany NY), 8: 3–11.
[9] Prather AA, Gurfein B, Moran P, Daubenmier J, Acree M, Bacchetti P, et al. (2015). Tired telomeres: Poor global sleep quality, perceived stress, and telomere length in immune cell subsets in obese men and women. Brain Behav Immun, 47: 155–62.
[10] Tempaku PF, Mazzotti DR, Tufik S (2015). Telomere length as a marker of sleep loss and sleep disturbances: a potential link between sleep and cellular senescence. Sleep Med, 16: 559–63.
[11] Cribbet MR, Carlisle M, Cawthon RM, Uchino BN, Williams PG, Smith TW, et al. (2014). Cellular aging and restorative processes: subjective sleep quality and duration moderate the association between age and telomere length in a sample of middle-aged and older adults. Sleep, 37: 65–70.
[12] Carroll JE, Esquivel S, Goldberg A, Seeman TE, Effros RB, Dock J, et al. (2016). Insomnia and telomere length in older adults. Sleep, 39: 559–64.
[13] Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C, et al. (1999). Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell, 96: 701–12.
[14] Rasmussen LD, May MT, Kronborg G, Larsen CS, Pedersen C, Gerstoft J, et al. (2015). Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study. Lancet HIV, 2: e288–298.
[15] Cohen J, Torres C (2017). HIV-associated cellular senescence: a contributor to accelerated aging. Ageing Res Rev, 36: 117–24.
[16] Lagathu C, Cossarizza A, Béréziat V, Nasi M, Capeau J, Pinti M (2017). Basic science and pathogenesis of ageing with HIV: potential mechanisms and biomarkers. AIDS, 31 Suppl 2: S105–S119.
[17] Nasi M, De Biasi S, Gibellini L, Bianchini E, Pecorini S, Bacca V, et al. (2017). Ageing and inflammation in patients with HIV infection. Clin Exp Immunol, 187: 44–52.
[18] Masiá M, Padilla S, Fernández M, Barber X, Moreno S, Iribarren JA, et al. (2017). Contribution of oxidative stress to non-AIDS events in HIV-infected patients. J Acquir Immune Defic Syndr, 75: e36–e44.
[19] Pathai S, Lawn SD, Gilbert CE, McGuinness D, McGlynn L, Weiss HA, et al. (2013). Accelerated biological ageing in HIV-infected individuals in South Africa: a case-control study. AIDS, 27: 2375–84.
[20] Zanet DL, Thorne A, Singer J, Maan EJ, Sattha B, Le Campion A, et al; CIHR Emerging Team Grant on HIV Therapy and Aging: CARMA. (2014). Association between short leukocyte telomere length and HIV infection in a cohort study: No evidence of a relationship with antiretroviral therapy. Clin Infect Dis, 58: 1322–32.
[21] Crum-Cianflone NF, Roediger MP, Moore DJ, Hale B, Weintrob A, Ganesan A, et al. (2012). Prevalence and factors associated with sleep disturbances among early-treated HIV-infected persons. Clin Infect Dis, 54: 1485–94.
[22] Jean-Louis G, Weber KM, Aouizerat BE, Levine AM, Maki PM, Liu C, et al. (2012). Insomnia symptoms and HIV infection among participants in the Women’s Interagency HIV Study. Sleep, 35: 131–7.
[23] Low Y, Goforth H, Preud'homme X, Edinger J, Krystal A (2014). Insomnia in HIV-infected patients: pathophysiologic implications. AIDS Rev, 16: 3–13.
[24] Wikgren M, Maripuu M, Karlsson T, Nordfjäll K, Bergdahl J, Hultdin J, et al. (2012). Short telomeres in depression and the general population are associated with a hypocortisolemic state. Biol Psychiatry, 71: 294–300.
[25] Brothers TD, Kirkland S, Guaraldi G, Falutz J, Theou O, Johnston BL, et al. (2014). Frailty in people aging with human immunodeficiency virus (HIV) infection. J Infect Dis, 210: 1170–9.
[26] Lee KA, Gay C, Humphreys J, Portillo CJ, Pullinger CR, Aouizerat BE (2014). Telomere length is associated with sleep duration but not sleep quality in adults with human immunodeficiency virus. Sleep, 37: 157–66.
[27] Ding Y, Lin H, Liu X, Wong FY, Sun YV, Marconi VC, et al. (2017). Higher prevalence of frailty among a sample of Chinese HIV-infected middle-aged and older adults is associated with neurocognitive impairment and depressive symptoms. J Infect Dis, 215: 687–92.
[28] Ding Y, Lin H, Liu X, Zhang Y, Wong FY, Sun YV, et al. (2017). Hypertension in HIV-Infected adults compared with similar but uninfected adults in China: body mass index-dependent effects of nadir CD4 count. AIDS Res Hum Retroviruses, 33:1117–25.
[29] Zhang F, Zhu H, Wu Y, Dou Z, Zhang Y, Kleinman N, et al. (2014). HIV, hepatitis B virus, and hepatitis C virus co-infection in patients in the China National Free Antiretroviral Treatment Program, 2010-12: a retrospective observational cohort study. Lancet Infect Dis, 14: 1065–72.
[30] Xiao Y, Liu Y, Yang Y, Yang Y, Fan S, Yang C, et al. (2016). Relationship between hypertension and body mass index, waist circumference and waist-hip ratio in middle-aged and elderly residents. Chin J Epidemiol, 37: 1227.
[31] Jenkins CD, Stanton BA, Niemcryk SJ, Rose RM (1988). A scale for the estimation of sleep problems in clinical research. J Clin Epidemiol, 41: 313–21.
[32] Zung WWK (1965). A self-rating depression scale. Arch Gen Psychiatry, 12:63–70.
[33] Li L, Ji G, Liang LJ, Ding Y, Tian J, Xiao Y (2011). A multi-level intervention for HIV affected families: together for empowerment activities (TEA). Soc Sci Med, 73:1214–21
[34] Cawthon RM (2002). Telomere measurement by quantitative PCR. Nucleic Acids Res, 30: e47.
[35] Lin J, Epel E, Cheon J, Kroenke C, Sinclair E, Bigos M, et al. (2010). Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance. J Immunol Methods, 352: 71–80.
[36] Campisi J, d'Adda di Fagagna F (2007). Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol, 8:729–40.
[37] Hodes RJ, Sierra F, Austad SN, Epel E, Neigh GN, Erlandson KM (2016). Disease drivers of aging. Ann N Y Acad Sci, 1386: 45–68.
[38] Garland S, Palmer C, Donelson M, Gehrman P, Johnson FB, Mao J (2014). A nested case-controlled comparison of telomere length and psychological functioning in breast cancer survivors with and without insomnia symptoms. Rejuvenation Res, 17:453–7.
[39] Kooij KW, Wit FW, Schouten J, van der Valk M, Godfried MH, Stolte IG, et al. (2016). HIV infection is independently associated with frailty in middle-aged HIV type 1-infected individuals compared with similar but uninfected controls. AIDS, 30: 241–50.
[40] Gallego L, Barreiro P, del Rio R, Gonzalez de Requena D, Rodriguez-Albarino A, et al. (2004). Analyzing sleep abnormalities in HIV-infected patients treated with efavirenz. Clin Infect Dis, 38: 430–32.
[41] Sherr L, Harding R, Lampe F, Johnson M, Anderson J, Zetler S, et al. (2009). Clinical and behavioural aspects of aging with HIV infection. Psychol Health Med, 14: 273–9.
[42] Huang X, Li H, Meyers K, Xia W, Meng Z, Li C, et al. (2017). Burden of sleep disturbances and associated risk factors: A cross-sectional survey among HIV-infected persons on antiretroviral therapy across China. Sci Rep, 7: 3657.
[43] Allavena C, Guimard T, Billaud E, de la Tullaye S, Reliquet V, Pineau S, et al. (2014). Prevalence and risk factors of sleep disturbances in a large HIV-infected adult population. J Int AIDS Soc, 17(4 Suppl 3):19576.
[44] Xiang YT, Ma X, Cai ZJ, Li SR, Xiang YQ, Guo HL, et al. (2008). The prevalence of insomnia, its sociodemographic and clinical correlates, and treatment in rural and urban regions of Beijing, China: a general population-based survey. Sleep, 31: 1655–62.
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