Sleep Deprivation and Divergent Toll-like Receptor-4 Activation of Cellular Inflammation in Aging
Open accessAbstract
OBJECTIVES: Sleep disturbance and aging are associated with increases in inflammation, as well as increased risk of infectious disease. However, there is limited understanding of the role of sleep loss on age-related differences in immune responses. This study examines the effects of sleep deprivation on toll-like receptor activation of monocytic inflammation in younger compared to older adults. DESIGN, SETTING, AND PARTICIPANTS: Community-dwelling adults (n = 70) who were categorized as younger (25-39 y old, n = 21) and older (60-84 y old, n = 49) participants, underwent a sleep laboratory-based experimental partial sleep deprivation (PSD) protocol including adaptation, an uninterrupted night of sleep, sleep deprivation (sleep restricted to 03:00-07:00), and recovery. MEASUREMENT AND RESULTS: Blood samples were obtained each morning to measure toll-like receptor-4 activation of monocyte intracellular production of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Partial sleep deprivation induced a significant increase in the production of IL-6 and/or TNF-α that persisted after a night of recovery sleep (F(2,121.2) = 3.8, P < 0.05). Age moderated the effects of sleep loss, such that younger adults had an increase in inflammatory cytokine production that was not present in older adults (F(2,121.2) = 4.0, P < 0.05). CONCLUSION: Older adults exhibit reduced toll-like receptor 4 stimulated cellular inflammation that, unlike in younger adults, is not activated after a night of partial sleep loss. Whereas sleep loss increases cellular inflammation in younger adults and may contribute to inflammatory disorders, blunted toll-like receptor activation in older adults may increase the risk of infectious disease seen with aging.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Only the oldest age group (>70 yr) had shorter PBMC telomere length when diagnostic criteria of insomnia were fulfilled.
“only the oldest age group (>70 yr) had shorter PBMC telomere length when diagnostic criteria of insomnia were fulfilled”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [90]
The presence of insomnia may accelerate cellular aging in the later years of life.
“suggesting that the presence of insomnia may accelerate cellular aging in the later years of life”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [90]
In the oldest age group (>70 yr) within a sample of 126 older adults, a diagnosis of primary insomnia was associated with shorter PBMC telomere length.
“In the oldest age group (>70 yr) within a sample of 126 older adults, a diagnosis of primary insomnia (based on DSM-IV criteria) was associated with shorter PBMC telomere length”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [90]
Cites
The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research
Buysse, D. J., Reynolds, C. F., Monk, T. H., Berman, S. R., & Kupfer, D. J. (1989) · Psychiatry Research · doi:10.1016/0165-1781(89)90047-4 · Cited by 35,234 · see citing works
Rechtschaffen, A. (1968) · Medical Entomology and Zoology · Cited by 11,772 · see citing works
Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation
Beck, A. T., Steer, R. A., & Carbin, M. G. (1988) · Clinical Psychology Review · doi:10.1016/0272-7358(88)90050-5 · Cited by 11,696 · see citing works
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312 · see citing works
Hobson, J. A. (1969) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(69)90021-2 · Cited by 5,215 · see citing works
Ohayon, M. M., Carskadon, M. A., Guilleminault, C., & Vitiello, M. V. (2004) · Sleep · doi:10.1093/sleep/27.7.1255 · Cited by 3,349 · see citing works
Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.
Howren, M. B., Lamkin, D. M., & Suls, J. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181907c1b · Cited by 2,766 · see citing works
Cappuccio, F. P., Cooper, D., D'Elia, L., Strazzullo, P., & Miller, M. A. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr007 · Cited by 2,146 · see citing works
Vaccine Adjuvants: Putting Innate Immunity to Work
Coffman, R. L., Sher, A., & Seder, R. A. (2010) · Immunity · doi:10.1016/j.immuni.2010.10.002 · Cited by 1,927 · see citing works
Molecular inflammation: Underpinnings of aging and age-related diseases
Chung, H. Y., Cesari, M., Anton, S., Marzetti, E., Giovannini, S., Seo, A. Y., Carter, C., Yu, B. P., & Leeuwenburgh, C. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2008.07.002 · Cited by 1,203 · see citing works
Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk
Meier-Ewert, H. K., Ridker, P. M., Rifai, N., Regan, M. M., Price, N. J., Dinges, D. F., & Mullington, J. M. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.07.050 · Cited by 1,195 · see citing works
Age-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,180 · see citing works
Besedovsky, L., Lange, T., & Born, J. (2012) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-011-1044-0 · Cited by 1,153 · see citing works
Adverse Effects of Modest Sleep Restriction on Sleepiness, Performance, and Inflammatory Cytokines
Vgontzas, A. N., Zoumakis, E., Bixler, E. O., Lin, H.-M., Follett, H., Kales, A., & Chrousos, G. P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031562 · Cited by 1,050 · see citing works
The interface between innate and adaptive immunity
Hoebe, K. H. N., Janssen, E. M., & Beutler, B. (2004) · Nature Immunology · doi:10.1038/ni1004-971 · Cited by 919 · see citing works
Sleep Deprivation and Activation of Morning Levels of Cellular and Genomic Markers of Inflammation
Irwin, M. R. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.16.1756 · Cited by 850 · see citing works
Self-citationCardiovascular, inflammatory, and metabolic consequences of sleep deprivation
Mullington, J. M., Haack, M., Toth, M., Serrador, J. M., & Meier-Ewert, H. K. (2009) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2008.10.003 · Cited by 783 · see citing works
Haack, M., Sanchez, E., & Mullington, J. M. (2007) · Sleep · doi:10.1093/sleep/30.9.1145 · Cited by 615 · see citing works
Sleep habits and susceptibility to the common cold
Cohen, S., Doyle, W. J., Alper, C. M., Janicki-Deverts, D., & Turner, R. B. (2009) · Archives of Internal Medicine · doi:10.1001/archinternmed.2008.505 · Cited by 605 · see citing works
Effects of sleep and circadian rhythm on the human immune system
Lange, T., Dimitrov, S., & Born, J. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05300.x · Cited by 591 · see citing works
Mullington, J. M., Simpson, N. S., Meier-Ewert, H. K., & Haack, M. (2010) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.08.014 · Cited by 519 · see citing works
Sleep Loss Activates Cellular Inflammatory Signaling
Irwin, M. R., Wang, M., Ribeiro, D., Cho, H. J., Olmstead, R., Breen, E. C., Martinez-Maza, O., & Cole, S. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.05.004 · Cited by 467 · see citing works
Self-citationShearer, W. T., Reuben, J. M., Mullington, J. M., Price, N. J., Lee, B.-N., Smith, E. O., Szuba, M. P., Van Dongen, H. P. A., & Dinges, D. F. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.112270 · Cited by 455 · see citing works
Biology of Immune Responses to Vaccines in Elderly Persons
Weinberger, B., Herndler‐Brandstetter, D., Schwanninger, A., Weiskopf, D., & Grubeck‐Loebenstein, B. (2008) · Clinical Infectious Diseases · doi:10.1086/529197 · Cited by 392 · see citing works
Redwine, L. S., Hauger, R. L., Gillin, J. C., & Irwin, M. R. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.10.6871 · Cited by 373 · see citing works
Self-citationSleep Enhances the Human Antibody Response to Hepatitis A Vaccination
Lange, T., Perras, B., Fehm, H. L., & Born, J. (2003) · Psychosomatic Medicine · doi:10.1097/01.psy.0000091382.61178.f1 · Cited by 351 · see citing works
The role of CD8<sup>+</sup> T‐cell replicative senescence in human aging
Effros, R. B., Dagarag, M., Spaulding, C., & Man, J. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00259.x · Cited by 336 · see citing works
The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults
Frey, D. J., Fleshner, M., & Wright, K. P. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.04.003 · Cited by 330 · see citing works
T Cell Replicative Senescence in Human Aging
P. Chou, J., & B. Effros, R. (2013) · Current Pharmaceutical Design · doi:10.2174/138161213805219711 · Cited by 323 · see citing works
Sleep loss activates cellular markers of inflammation: Sex differences
Irwin, M. R., Carrillo, C., & Olmstead, R. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.06.001 · Cited by 287 · see citing works
Self-citationRedwine, L. S. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.10.3597 · Cited by 285 · see citing works
Boehmer, E. D., Góral, J., Faunce, D. E., & Kovacs, E. J. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0803389 · Cited by 266 · see citing works
Impact of acute sleep restriction on cortisol and leptin levels in young women
Omisade, A., Buxton, O. M., & Rusak, B. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.01.028 · Cited by 235 · see citing works
Vgontzas, A. N., Zoumakis, M., Bixler, E. O., Lin, H.-M., Prolo, P., Vela‐Bueno, A., Kales, A., & Chrousos, G. P. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021176 · Cited by 235 · see citing works
Sleep deprivation and human immune function
Dinges, D. F., Douglas, S. D., Hamarman, S., Zaugg, L., & Kapoor, S. C. (1995) · Advances in Neuroimmunology · doi:10.1016/0960-5428(95)00002-j · Cited by 234 · see citing works
Disrupting the circadian clock: Gene-specific effects on aging, cancer, and other phenotypes
Yu, E. A., & Weaver, D. R. (2011) · Aging · doi:10.18632/aging.100323 · Cited by 228 · see citing works
Sleep Complaints in Community‐Living Older Persons: A Multifactorial Geriatric Syndrome
Fragoso, C. A. V., & Gill, T. M. (2007) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01399.x · Cited by 224 · see citing works
Gangwisch, J. E., Heymsfield, S. B., Boden-Albala, B. M., Buijs, R. M., Kreier, F., Opler, M. G., Pickering, T. G., Rundle, A., Zammit, G. K., & Malaspina, D. (2008) · SLEEP · doi:10.5665/sleep/31.8.1087 · Cited by 213 · see citing works
Sleep and Antibody Response to Hepatitis B Vaccination
Prather, A. A., Hall, M., Fury, J. M., Ross, D. C., Muldoon, M. F., Cohen, S., & Marsland, A. L. (2012) · SLEEP · doi:10.5665/sleep.1990 · Cited by 207 · see citing works
Pejovic, S., Basta, M., Vgontzas, A. N., Kritikou, I., Shaffer, M. L., Tsaoussoglou, M., Stiffler, D., Stefanakis, Z., Bixler, E. O., & Chrousos, G. P. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00301.2013 · Cited by 166 · see citing works
Stress-induced glucocorticoids as a neuroendocrine alarm signal of danger
Frank, M. G., Watkins, L. R., & Maier, S. F. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.02.004 · Cited by 160 · see citing works
The effect of sleep fragmentation on sleep and performance in younger and older subjects
Bonnet, M. H. (1989) · Neurobiology of Aging · doi:10.1016/s0197-4580(89)80006-5 · Cited by 129 · see citing works
Disordered Sleep, Nocturnal Cytokines, and Immunity in Alcoholics
Redwine, L., Dang, J., Hall, M., & Irwin, M. (2003) · Psychosomatic Medicine · doi:10.1097/01.psy.0000038943.33335.d2 · Cited by 109 · see citing works
Self-citationSleep Deprivation in Healthy Elderly Men and Women: Effects on Mood and on Sleep During Recovery
Reynolds, C. F., Kupfer, D. J., Hoch, C. C., STACK, J. A., Houck, P. R., & Berman, S. (1986) · SLEEP · doi:10.1093/sleep/9.4.492 · Cited by 102 · see citing works
Bonnet, M. H., & Rosa, R. R. (1987) · Biological Psychology · doi:10.1016/0301-0511(87)90035-4 · Cited by 98 · see citing works
Irwin, M., Rinetti, G., Redwine, L., Motivala, S., Dang, J., & Ehlers, C. (2004) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2004.02.001 · Cited by 95 · see citing works
Self-citationCircadian regulation of cell cycle: Molecular connections between aging and the circadian clock
Khapre, R. V., Samsa, W. E., & Kondratov, R. V. (2010) · Annals of Medicine · doi:10.3109/07853890.2010.499134 · Cited by 95 · see citing works
Major depressive disorder and immunity to varicella-zoster virus in the elderly
Irwin, M. R., Levin, M. J., Carrillo, C., Olmstead, R., Lucko, A., Lang, N., Caulfield, M. J., Weinberg, A., Chan, I. S. F., Clair, J. B. S., et al. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.02.001 · Cited by 83 · see citing works
Self-citationSleep deprivation as a probe of homeostatic sleep regulation in primary alcoholics
Irwin, M. R., Gillin, J. C., Dang, J., Weissman, J., Phillips, E., & Ehlers, C. L. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01304-x · Cited by 72 · see citing works
Self-citationThe role of CD8 T cell replicative senescence in human aging.
Effros, R. B. (2005) · PubMed · Cited by 41 · see citing works
Kuo, T., & Williams, J. A. (2014) · SLEEP · doi:10.5665/sleep.3648 · Cited by 34 · see citing works
Murillo-Ortiz, B. O., Albarrán-Tamayo, F., López-Briones, S., Martı́nez-Garza, S., Benı́tez-Bribiesca, L., & Arenas-Aranda, D. J. (2013) · BMC Geriatrics · doi:10.1186/1471-2318-13-99 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Sleep-Immune Crosstalk in Health and Disease
Besedovsky, L., Lange, T., & Haack, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00010.2018 · Cited by 1,479 · see citing works
Sleep health: Reciprocal regulation of sleep and innate immunity
Irwin, M. R., & Opp, M. R. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.148 · Cited by 624 · see citing works
Self-citationCarroll, J. E., Cole, S. W., Seeman, T. E., Breen, E. C., Witarama, T., Arevalo, J. M. G., Ma, J., & Irwin, M. R. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.08.024 · Cited by 129 · see citing works
Self-citation
- Authors
- Carroll, J. E., Carrillo, C., Olmstead, R., Witarama, T., Breen, E. C., Yokomizo, M., Seeman, T. E., & Irwin, M. R.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Carroll, Judith E.
- Venue
- Sleep
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-02-01
- Volume
- 38
- Issue
- 2
- Pages
- 205-211
- ISSN
- 0161-8105 (ISSN-L)
- 1550-9109
- PMC
- PMC4288601
- OpenAlex
- W2062286859
- Cited by
- 67
- References
- 52
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 11 · 2023: 2 · 2022: 11 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 1
- FWCI
- 5.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- SLEEP (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Sleep Medicine Foundation
- National Health and Aging Trends Study
- National Institutes of Health (UL1TR000124)
- Center for Clinical and Translational Research
- National Institute on Aging (R01AG026364, R01AG034588, P30AG028748)
- National Heart, Lung, and Blood Institute (R01HL095799)
- National Institute of Mental Health (T32MH019925, T32 MH 19925)
- National Institute on Drug Abuse (R01DA032922)
- National Cancer Institute (R01CA160245, R01CA119159)
- NIH Clinical Center
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep deprivation, sleep restriction, TLR4, aging, age differences, monocyte inflammation, interleukin-6, TNF-α, inflammatory cytokines, recovery sleep, infectious disease risk
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Communicable Diseases, Female, Humans, Inflammation, Male, Middle Aged, Monocytes, Sleep, Sleep Deprivation, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Toll-Like Receptor 4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
