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Record W4380480297 · doi:10.1038/s41467-023-38238-6

Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection

2023· article· en· W4380480297 on OpenAlexafffund
Sunil K. Ahuja, Muthu Saravanan Manoharan, Grace C. Lee, Lyle R. McKinnon, Justin A. Meunier, Maristella Steri, Nathan Harper, Edoardo Fiorillo, Alisha M. Smith, Marcos I. Restrepo, Anne P. Branum, Matthew J. Bottomley, Valeria Orrù, Fabio Jiménez, Andrew Carrillo, Lavanya Pandranki, Caitlyn Winter, Lauryn Winter, Alvaro A. Gaitan, Alvaro Moreira, Elizabeth Walter, Guido Silvestri, Christopher L. King, Yong‐Tang Zheng, Hong‐Yi Zheng, Joshua Kimani, T. Blake Ball, Francis A. Plummer, Keith R. Fowke, Paul Harden, Kathryn J. Wood, Martin T. Ferris, Jennifer M. Lund, Mark T. Heise, Nigel Garrett, Kristen R. Canady, Salim S. Abdool Karim, Susan J. Little, Sara Gianella, Davey M. Smith, Scott Letendre, Douglas D. Richman, Francesco Cucca, Hanh Trinh, Sandra Sanchez‐Reilly, Joan M. Hecht, Jose A. Cadena Zuluaga, Antonio Anzueto, Jacqueline A. Pugh, Mohamed I. Abdalla, Sylvia Adams, Yemi Adebayo, Joseph Agnew, Saleem Ali, Gregory M. Anstead, Marichu Balmes, Jennifer M. Barker, Deborah Baruch-Bienen, Velma Bible, Angela Birdwell, Stacy Braddy, Stephen Bradford, H. Briggs, Judith Martín Corral, Jennifer J. Dacus, Patrick Danaher, Scott A. DePaul, Jill Dickerson, Jollynn Doanne, Aamir Ehsan, Samantha Elbel, Miguel Escalante, Corina Escamilla, Valerie Escamilla, Robert Farrar, David Feldman, Debra Flores, Julianne Flynn, Delvina Ford, Joanna D. Foy, Megan Culler Freeman, Samantha Galley, Jessica Medina García, Maritza Garza, S. Douglass Gilman, Melanie Goel, Jennifer M. Gómez, Varun Goyal, Sally Grassmuck, S Grigsby, Joshua A. Hanson, Brande Harris, Audrey Haywood, Cecilia A. Hinojosa, Tony T. Ho, Teri Hopkins, Lynn L. Horvath, Aneela Hussain, Ali Jabur, Pamela Jewell, Thomas Johnson, Austin C. Lawler, Monica Lee, Chadwick S. Lester, Stephanie M. Levine, Haidee V. Lewis, Angel Louder, Charmaine Mainor, Rachel Maldonado, Celida Martinez, Yvette Martinez, Diego J. Maselli, C. Mata, Neil McElligott, Laura Medlin, Myra Mireles, Joanna Moreno, Kathleen Morneau, Julie Muetz, Samuel B. Munro, Charlotte Murray, Anoop M. Nambiar, Daniel Nassery, Robert Nathanson, Kimberly Oakman, Jane O’Rorke, Cheryl Padgett, Sergi Pascual-Guàrdia, Marisa Patterson, Graciela Pérez, Rogelio Perez, R. E. Phillips, Patrick B. Polk, Michael A. Pomager, Kristy J. Preston, Kevin C. Proud, Michelle Rangel, Temple Ratcliffe, Renee L. Reichelderfer, Evan M. Renz, Jeanette Ross, Teresa Rudd, M. E. Sánchez, Tammy Sanders, Kevin C. Schindler, David Schmit, Raj Sehgal, Claudio Solorzano, Nilam J. Soni, Win S. Tam, Edward J. Tovar, Sadie A. Trammell Velasquez, Anna R. Tyler, Anjuli Vasquez, Maria C. Veloso, Steven G. Venticinque, Jorge A. Villalpando, Melissa Villanueva, Lauren Villegas, Megan Walker, Andrew Wallace, Maria Wallace, Emily Wang, Stephanie Wickizer, Andreia Williamson, Andrea Yunes, Katharine H. Zentner, Brian K. Agan, Robert Root‐Bernstein, Robert A. Clark, Jason F. Okulicz, Weijing He

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsUniversity of Manitoba
FundersNational Institute of Dental and Craniofacial ResearchNational Institute of Allergy and Infectious DiseasesNHLBI Division of Intramural ResearchMax and Minnie Tomerlin Voelcker FundNational Institute on Drug AbuseNational Institute for Health and Care ResearchNational Institute on AgingCanadian Institutes of Health ResearchU.S. Department of Veterans AffairsUniversity of California, San DiegoNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteUniformed Services University of the Health SciencesU.S. Air ForceNational Key Research and Development Program of ChinaMinistero dell’Istruzione, dell’Università e della RicercaWellcome TrustNational Natural Science Foundation of ChinaU.S. Department of DefenseEuropean CommissionBill and Melinda Gates FoundationNational Institute of General Medical Sciences59th Medical WingHenry M. Jackson FoundationNational Institutes of HealthU.S. Department of Health and Human ServicesNational Center for Advancing Translational SciencesElizabeth Glaser Pediatric AIDS Foundation
KeywordsImmunocompetenceLongevityImmune systemInflammationImmunologyImmunityMedicineSepsisStressorBiologyGerontology

Abstract

fetched live from OpenAlex

Abstract Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8 + and CD4 + T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.058
GPT teacher head0.352
Teacher spread0.294 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations91
Published2023
Admission routes2
Has abstractyes

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