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Cellular signaling in the aging immune system
Abstract
Causes for immunosenescence and inflamm-aging have to be established. Efficient function of the immune system requires homeostatic regulation from receptor recognition of antigenic challenge to cell responses and adaptation to its changing environment. It is reasonable to assume that one of the most important molecular causes of immunosenescence is alteration in the regulation of signaling pathways. Indeed, alterations in feed-forward and negative feedback (inhibitory) signaling have been highlighted in all cells involved in the immune response including short-lived (neutrophils) and long-lived (T lymphocytes) cells. These dysregulations tip the balance in favor of altered (less efficient) function of the immune system. In this review, we summarize our knowledge on signal transduction changes in the aging immune system and propose a unifying mechanism as one of the causes of immunosenescence. Modulation of these pathways with aging represents a major challenge to restore the immune response to functional levels.
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“Studies of human T cells have associated aging with changes in autophagy, in membrane properties to form rafts, and in reactive oxygen production (Fulop et al., 2014; Phadwal et al., 2012); however, these studies examined total T cell populations, irrespective of naive or memory phenotypes, and are therefore difficult to interpret.”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Fulop et al., 2014
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“In almost all immune cells, one of the most prominent changes occurring with aging regards signaling, that is integrating all the molecular events converging from the surface receptors to an adequate cellular response [132].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [132]
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Metadata
- Authors
- Fulop, T., Le Page, A., Fortin, C., Witkowski, J. M., Dupuis, G., & Larbi, A.
- Affiliations
- Université de Sherbrooke (CA)
- Gdańsk Medical University (PL)
- Agency for Science, Technology and Research (SG)
- Venue
- Current Opinion in Immunology
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 29
- Pages
- 105-111
- ISSN
- 0952-7915 (ISSN-L)
- OpenAlex
- W2049865778
- Cited by
- 158
- References
- 85
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 10 · 2023: 4 · 2022: 16 · 2021: 14 · 2020: 13 · 2019: 14 · 2018: 16 · 2017: 20 · 2016: 17 · 2015: 20 · 2014: 6
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (106634, 106701)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- immunosenescence, inflammaging, signal transduction, aging immune system, negative feedback signaling, feed-forward signaling, T cells, neutrophils, immune homeostasis
- MeSH terms
- Aging, Animals, Humans, Neutrophils, Oxidation-Reduction, Receptors, Antigen, T-Cell, T-Lymphocytes, Signal Transduction
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