Upregulated ex vivo expression of stress-responsive inflammatory pathway genes by LPS-challenged CD14(+) monocytes in frail older adults
Open accessAbstract
Frailty has been increasingly recognized as an important clinical syndrome in old age. The frailty syndrome is characterized by chronic inflammation, decreased functional and physiologic reserve, and increased vulnerability to stressors, leading to disability and mortality. However, molecular mechanisms that contribute to inflammation activation and regulation in frail older adults have not been investigated. To begin to address this, we conducted a pathway-specific gene array analysis of 367 inflammatory pathway genes by lipopolysaccharide (LPS)-challenged CD14(+) monocytes from 32 community-dwelling frail and age-, race-, and sex-paired nonfrail older adults (mean age 83 years, range 72-94). The results showed that ex vivo LPS-challenge induced average 2.0-fold or higher upregulated expression of 116 genes in frail participants and 85 genes in paired nonfrail controls. In addition, frail participants had 2-fold or higher upregulation in LPS-induced expression of 7 stress-responsive genes than nonfrail controls with validation by quantitative real time RT-PCR. These findings suggest upregulated expression of specific stress-responsive genes in monocyte-mediated inflammatory pathway in the syndrome of frailty with potential mechanistic and interventional implications.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Several inflammatory markers-IL-6, CRP, TNFα and CXCL-10 among them-have each been independently linked to frailty.
“A range of inflammatory cytokines have been independently associated with frailty including interleukin-6 (IL-6), C-reactive protein (CRP), tumour necrosis factor-α (TNFα) and CXC chemokine ligand-10 (CXCL-10), a potent pro-inflammatory mediator (52, 54-58).”
From Frailty in elderly people (2013) · cites this paper as [56]
Inflammation appears central to frailty via an abnormal low-grade state that overreacts to stimuli and remains active long after the trigger is gone.
“There is evidence that inflammation has a key role in the pathophysiology of frailty through an abnormal, low-grade inflammatory response that is hyper-responsive to stimuli and that persists for a prolonged period following removal of the initial inflammatory stimulus (19, 52-57).”
From Frailty in elderly people (2013) · cites this paper as [56]
Classical monocytes from frail older adults show increased expression of inflammation-associated genes after LPS stimulation compared with non-frail older adults.
“Classical monocytes isolated from frail older adults had increased inflammatory associated genes in response to LPS as compared to non-frail older adults (140).”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [140]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Frailty in Older Adults: Evidence for a Phenotype
Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W. J., Burke, G., et al. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.3.m146 · Cited by 24,907 · see citing works
Self-citationThe Pathophysiology and Treatment of Sepsis
Hotchkiss, R. S., & Karl, I. E. (2003) · New England Journal of Medicine · doi:10.1056/nejmra021333 · Cited by 4,098 · see citing works
Fried, L. P., Ferrucci, L., Darer, J., Williamson, J. D., & Anderson, G. (2004) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/59.3.m255 · Cited by 4,032 · see citing works
Self-citationThe many roles of chemokines and chemokine receptors in inflammation
Charo, I. F., & Ransohoff, R. M. (2006) · New England Journal of Medicine · doi:10.1056/nejmra052723 · Cited by 2,523 · see citing works
Gerard, C., & Rollins, B. J. (2001) · Nature Immunology · doi:10.1038/84209 · Cited by 1,357 · see citing works
Phenotype of frailty: characterization in the women's health and aging studies
Bandeen-Roche, K., Xue, Q.-L., Ferrucci, L., Walston, J., Guralnik, J. M., Chaves, P., Zeger, S. L., & Fried, L. P. (2006) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/61.3.262 · Cited by 1,215 · see citing works
Self-citationB7-H3: A costimulatory molecule for T cell activation and IFN-γ production
Chapoval, A. I., Ni, J., Lau, J. S., Wilcox, R. A., Flies, D. B., Liu, D., Dong, H., Sica, G., Zhu, G., Tamada, K., et al. (2001) · Nature Immunology · doi:10.1038/85339 · Cited by 1,016 · see citing works
Walston, J. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.20.2333 · Cited by 940 · see citing works
Self-citationAnti-inflammatory lipid mediators and insights into the resolution of inflammation
Lawrence, T., Willoughby, D. A., & Gilroy, D. W. (2002) · Nature reviews. Immunology · doi:10.1038/nri915 · Cited by 863 · see citing works
Interleukin-6 in Aging and Chronic Disease: A Magnificent Pathway
Maggio, M. G., Guralnik, J. M., Longo, D. L., & Ferrucci, L. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.6.575 · Cited by 687 · see citing works
Self-citationDynamics of stability: the physiologic basis of functional health and frailty
Lipsitz, L. A. (2002) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/57.3.b115 · Cited by 646 · see citing works
Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity
Gray, P. W., Aggarwal, B. B., Benton, C. V., Bringman, T. S., Henzel, W. J., Jarrett, J. A., Leung, D. W., Moffat, B., Ng, P., Svedersky, L. P., et al. (1984) · Nature · doi:10.1038/312721a0 · Cited by 641 · see citing works
Sharif, S., Arreaza, G., Zucker, P., Mi, Q., Sondhi, J., Naidenko, O. V., Kronenberg, M., Koezuka, Y., Delovitch, T. L., Gombert, J., et al. (2001) · Nature Medicine · doi:10.1038/nm0901-1057 · Cited by 604 · see citing works
Inflammation and frailty in older women
Leng, S. X., Xue, Q., Tian, J., Walston, J. D., & Fried, L. P. (2007) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01186.x · Cited by 425 · see citing works
Self-citationLeng, S., Chaves, P., Koenig, K., & Walston, J. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50315.x · Cited by 387 · see citing works
Self-citationFrom Bedside to Bench: Research Agenda for Frailty
Fried, L. P., Hadley, E. C., Walston, J. D., Newman, A. B., Guralnik, J. M., Studenski, S. A., Harris, T. B., Ershler, W. B., & Ferrucci, L. (2005) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2005.31.pe24 · Cited by 299 · see citing works
Self-citationCappola, A. R., Xue, Q.-L., Ferrucci, L., Guralnik, J. M., Volpato, S., & Fried, L. P. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021694 · Cited by 286 · see citing works
Self-citationLeng, S. X., Cappola, A. R., Andersen, R. E., Blackman, M. R., Koenig, K., Blair, M., & Walston, J. D. (2004) · Aging Clinical and Experimental Research · doi:10.1007/bf03324545 · Cited by 270 · see citing works
Self-citationChaves, P. H. M., Semba, R. D., Leng, S. X., Woodman, R. C., Ferrucci, L., Guralnik, J. M., & Fried, L. P. (2005) · The Journals of Gerontology Series A · doi:10.1093/gerona/60.6.729 · Cited by 263 · see citing works
Self-citationStress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation
Viswanathan, K., & Dhabhar, F. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501650102 · Cited by 246 · see citing works
Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE
Suzuki, T., Hashimoto, S., Toyoda, N., Nagai, S., Yamazaki, N., Dong, H.-Y., Sakai, J., Yamashita, T., Nukiwa, T., & Matsushima, K. (2000) · Blood · doi:10.1182/blood.v96.7.2584 · Cited by 235 · see citing works
Serial Analysis of Gene Expression in Human Monocytes and Macrophages
Hashimoto, S., Suzuki, T., Dong, H.-Y., Yamazaki, N., & Matsushima, K. (1999) · Blood · doi:10.1182/blood.v94.3.837.413k02_837_844 · Cited by 232 · see citing works
Shibanuma, M., Mashimo, J., Kuroki, T., & Nose, K. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47085-8 · Cited by 209 · see citing works
Phenotypic and functional characteristics of circulating monocytes of elderly persons☆
Sadeghi, H. M., Schnelle, J. F., Thomas, J. K., Nishanian, P., & Fahey, J. L. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(99)00065-0 · Cited by 146 · see citing works
Sørensen, T. L., Sellebjerg, F. T., Jensen, C. V., Strieter, R. M., & Ransohoff, R. M. (2001) · European Journal of Neurology · doi:10.1046/j.1468-1331.2001.00327.x · Cited by 128 · see citing works
Martinis, M. D., Modesti, M., & Ginaldi, L. (2004) · Immunology and Cell Biology · doi:10.1111/j.0818-9641.2004.01242.x · Cited by 127 · see citing works
IL-10 expression profiling in human monocytes
Williams, L. M., Járai, G., Smith, A. J., & Finan, P. M. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.4.800 · Cited by 113 · see citing works
CXCR3-binding Chemokines: Novel Multifunctional Therapeutic Targets
Lazzeri, E., & Romagnani, P. (2005) · Current Drug Targets - Immune Endocrine & Metabolic Disorders · doi:10.2174/1568008053174723 · Cited by 113 · see citing works
Decreased cell proliferation and altered cytokine production in frail older adults
Leng, S. X., Yang, H., & Walston, J. D. (2004) · Aging Clinical and Experimental Research · doi:10.1007/bf03327392 · Cited by 101 · see citing works
Self-citationT‐Lymphocytes Expressing CC Chemokine Receptor‐5 Are Increased in Frail Older Adults
Fanis, U. D., Wang, G. C., Fedarko, N. S., Walston, J. D., Casolaro, V., & Leng, S. X. (2008) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2008.01673.x · Cited by 79 · see citing works
Self-citationMitogen activated protein kinase inhibitors: where are we now and where are we going?
Sweeney, S. E., & Firestein, G. S. (2006) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2006.058388 · Cited by 78 · see citing works
Sasaki, T., Wada, T., Kishimoto, H., Irie-Sasaki, J., Matsumoto, G., Goto, T., Yao, Z., Wakeham, A. C., Mak, T. W., Suzuki, A., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.6.757 · Cited by 64 · see citing works
Gramaglia, I., Mauri, D. N., Miner, K. T., et al. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.3.1333 · Cited by 59 · see citing works
Identification and Characterization of hic-5/ARA55 as an hsp27 Binding Protein
Jia, Y., Ransom, R. F., Shibanuma, M., Liu, C., Welsh, M. J., & Smoyer, W. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103510200 · Cited by 55 · see citing works
Gramaglia, I., Mauri, D. N., Miner, K. T., et al. (1999) · PubMed · Cited by 53 · see citing works
Zdanov, S., Remacle, J., & Toussaint, O. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1354.025 · Cited by 52 · see citing works
Heitzer, M. D., & DeFranco, D. B. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0065 · Cited by 50 · see citing works
Increased Monocyte Activation in Elderly Patients after Surgical Stress
Ono, S., Aosasa, S., Tsujimoto, H., Ueno, C., & Mochizuki, H. (2001) · European Surgical Research · doi:10.1159/000049690 · Cited by 43 · see citing works
Hu, Y., Cascone, P. J., Cheng, L., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.10218 · Cited by 42 · see citing works
Li, D.-P., Periyasamy, S., Jones, T. J., & Sánchez, E. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004502200 · Cited by 30 · see citing works
Barcellos‐Hoff, M. H. (2005) · British Journal of Radiology · doi:10.1259/bjr/26432956 · Cited by 30 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Fried LP, Walston J. Frailty. In: Halter JB, editor. Hazzard’s Principles of Geriatric Medicine and Gerontology. McGraw-Hill; Anne Arbor: 2007. [Google Scholar]
Cited by
Sorted by citations
Clegg, A., Young, J., Iliffe, S., Rikkert, M. O., & Rockwood, K. (2013) · The Lancet · doi:10.1016/s0140-6736(12)62167-9 · Cited by 9,503 · see citing works
Cellular senescence and the senescent secretory phenotype: therapeutic opportunities
Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., & Kirkland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64098 · Cited by 1,774 · see citing works
The impact of ageing on monocytes and macrophages
De Maeyer, R. P. H., & Chambers, E. S. (2021) · Immunology Letters · doi:10.1016/j.imlet.2020.12.003 · Cited by 275 · see citing works
Verschoor, C. P., Johnstone, J., Millar, J., Dorrington, M. G., Habibagahi, M., Lelic, A., Loeb, M., Bramson, J. L., & Bowdish, D. M. E. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.0912461 · Cited by 235 · see citing works
Dysregulation of human Toll-like receptor function in aging
Shaw, A. C., Panda, A., Joshi, S. R., Qian, F., Allore, H. G., & Montgomery, R. R. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2010.10.007 · Cited by 215 · see citing works
Yao, X., Hamilton, R. G., Weng, N.-P., Xue, Q.-L., Bream, J. H., Li, H., Tian, J., Yeh, S.-H., Resnick, B., Xu, X., et al. (2011) · Vaccine · doi:10.1016/j.vaccine.2011.04.077 · Cited by 189 · see citing works
Self-citationClinical strategies and animal models for developing senolytic agents
Kirkland, J. L., & Tchkonia, T. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.10.012 · Cited by 168 · see citing works
Discovery, development, and future application of senolytics: theories and predictions
Wissler Gerdes, E. O., Zhu, Y., Tchkonia, T., & Kirkland, J. L. (2020) · The FEBS Journal · doi:10.1111/febs.15264 · Cited by 160 · see citing works
Translating advances from the basic biology of aging into clinical application
Kirkland, J. L. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2012.11.014 · Cited by 128 · see citing works
Qu, T., Yang, H., Walston, J. D., Fedarko, N. S., & Leng, S. X. (2009) · Cytokine · doi:10.1016/j.cyto.2009.02.015 · Cited by 117 · see citing works
Self-citationTranslating the Science of Aging into Therapeutic Interventions
Kirkland, J. L. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025908 · Cited by 78 · see citing works
- Authors
- Qu, T., Walston, J. D., Yang, H., Fedarko, N. S., Xue, Q.-L., Beamer, B. A., Ferrucci, L., Rose, N. R., & Leng, S. X.
- Affiliations
- Johns Hopkins University (US)
- National Institute on Aging (US)
- Corresponding author
- Leng, Sean X.
- ORCID
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 130
- Issue
- 3
- Pages
- 161-166
- ISSN
- 0047-6374 (ISSN-L)
- PMC
- PMC2673566
- OpenAlex
- W2051391870
- Cited by
- 61
- References
- 41
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 AG999999)
- National Institute on Aging (R21AG024235, K23AG028963)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- frailty, older adults, CD14+ monocytes, lipopolysaccharide challenge, stress response genes, chronic inflammation, gene expression, monocyte activation
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Aging, Cells, Cultured, Female, Humans, Inflammation, Lipopolysaccharides, Male, Monocytes, Stress, Physiological, Reproducibility of Results, Up-Regulation, Case-Control Studies, Polymerase Chain Reaction, Frail Elderly, Inflammation Mediators, Lipopolysaccharide Receptors, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling
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
