Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Mar 2:8:100237.
doi: 10.1016/j.jtauto.2024.100237. eCollection 2024 Jun.

Autoimmunity in centenarians. A paradox

Juan-Manuel Anaya  1 , Ivan David Lozada-Martinez  1 , Isaura Torres  2 , Yehuda Shoenfeld  3
Affiliations
Review

Autoimmunity in centenarians. A paradox

Juan-Manuel Anaya et al. J Transl Autoimmun. .

Abstract

Autoimmune diseases (ADs) are one of the groups of chronic illnesses that impose a significant burden of disease and health costs worldwide. Age is a crucial risk factor for the onset of ADs. Theoretically, it is inferred that with organic and immune system aging, the loss of immune tolerance and specificity of immune activity becomes more intense, the probability of autoimmunity is increasing. However, there is a group of individuals whose prevalence of ADs is very low or non-existent, despite the biological aging. This paradox in autoimmunity raises questions. Centenarians, individuals who are over 100 years old, are possibly the most successful model of biological aging in humans. Most of these individuals exhibit a favorable health phenotype. To date, primary data evidence and potential hypotheses explaining this phenomenon are lacking globally, even though this paradox could provide valuable, original, and relevant information regarding the understanding of risk or protective factors, biological drivers, and biomarkers related to autoimmunity. Herein we discuss some hypothesis that may explain the absence of ADs in centenarians, including inflammaging, immunosenescence and immune resilience, immune system hyperstimulation, proteodynamics, and genetics.

Keywords: Autoimmune diseases; Autoimmunity; Centenarians; Genetics; Longevity; Proteodynamics.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
The development of autoimmunity through hyperstimulation from environmental factors. Abbreviations: EBV: Epstein-Barr virus; CMV: cytomegalovirus.
Fig. 2
Fig. 2
Factors associated with onset of ADs during longevity. Potential determinants are disclosed, which determine the quality of immune adaptation, balance, and remodeling (regulated or unregulated inflammaging) during the aging process (immunosenescence). The paradox is presented that, even in the presence of risk factors and immunosenescence, possibly the quality of proteodynamics (representing the quality, quantity, and activity of proteostasis) is essential in immune regulation during aging. This establishes a pattern of immune adaptation, balance, and remodeling, allowing the triggering of a regulated/unregulated inflammaging phenotype, leading to specific health outcomes in older adults (successful aging and protection against ADs or decline and premature death). Abbreviations: lnc-RNA: Long non-coding RNA; miRNA: MicroRNA; mRNA: Messenger RNA; tRNA: Transfer RNA.
Fig. 3
Fig. 3
Interacting factors that protect centenarians from autoimmune diseases.
See this image and copyright information in PMC

References

    1. Conrad N., Misra S., Verbakel J.Y., Verbeke G., Molenberghs G., Taylor P.N., Mason J., Sattar N., V McMurray J.J., McInnes I.B., Khunti K., Cambridge G. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. Lancet. 2023;401:1878–1890. doi: 10.1016/S0140-6736(23)00457-9. - DOI - PubMed
    1. Spierings J., Sloeserwij A., Vianen M.E., de Boer J.H., Sigurdsson V., van de Wijgert J.H.H.M., van Laar J.M. Health-related quality of life in patients with immune mediated inflammatory diseases: a cross-sectional, multidisciplinary study. Clin. Immunol. 2020;214 doi: 10.1016/j.clim.2020.108392. - DOI - PubMed
    1. Miller F.W. The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention. Curr. Opin. Immunol. 2023;80 doi: 10.1016/j.coi.2022.102266. - DOI - PMC - PubMed
    1. Anaya J.-M., Beltrán S. The autoimmune tautology revisited. J. Transl. Autoimmun. 2023;7 doi: 10.1016/j.jtauto.2023.100204. - DOI - PMC - PubMed
    1. Quintero O.L., Amador-Patarroyo M.J., Montoya-Ortiz G., Rojas-Villarraga A., Anaya J.-M. Autoimmune disease and gender: plausible mechanisms for the female predominance of autoimmunity. J. Autoimmun. 2012;38 doi: 10.1016/j.jaut.2011.10.003. J109–J119. - DOI - PubMed

LinkOut - more resources