Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence
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Key Points: Constitutive PI3K activity is associated with less accurate neutrophil migration in healthy aged adults. This is associated with increased primary granule release and neutrophil elastase activity and may contribute to inflammation and infection.
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Neutrophils from elderly individuals also show aberrant migration and enhanced degranulation.
“neutrophils from the elderly also display aberrant migration and enhanced degranulation”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [86]
Neutrophils from elderly subjects have reduced migration toward chemotactic signals, probably because of constitutive activation of PI3K.
“neutrophils from elderly subjects are characterized by a reduced capability to migrate towards a chemotactic signal, probably because of a constitutive activation of the lipid kinase phosphoinositide 3-kinase [PI3 K] [39]”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [39]
Inhibition of PI3K significantly improves neutrophil functions by restoring migratory accuracy in elderly subjects, whose PI3K signaling in resting neutrophils is constitutively increased.
“For example, it has been recently demonstrated that the inhibition of PI3K, whose signaling in resting human neutrophils is constitutively increased in elderly subjects, significantly improves their functions by restoring neutrophil migratory accuracy [39].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [39]
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- Authors
- Sapey, E., Greenwood, H., Walton, G., Mann, E., Love, A., Aaronson, N., Insall, R. H., Stockley, R. A., & Lord, J. M.
- Affiliations
- School of Clinical and Experimental Medicine and
- University of Birmingham (GB)
- Cancer Research UK Scotland Institute (GB)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2014-01-09
- Volume
- 123
- Issue
- 2
- Pages
- 239-248
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3888290
- OpenAlex
- W2054972774
- Cited by
- 358
- References
- 58
- Citations by year
- 2026: 18 · 2025: 27 · 2024: 35 · 2023: 27 · 2022: 28 · 2021: 45 · 2020: 33 · 2019: 22 · 2018: 37 · 2017: 29 · 2016: 24 · 2015: 17 · 2014: 16
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Cancer Research UK (15672)
- Academy of Medical Sciences (AMS-SGCL5-Sapey)
- Medical Research Council (MR/K00414X/1, MR/L008335/1)
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- immunosenescence, neutrophil migration, chemotaxis, chemokinesis, phosphatidylinositol 3-kinase, PI3Kγ inhibition, PI3Kδ inhibition, SHIP1, systemic inflammation, bacterial infection susceptibility, aging, older adults
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Adult, Age Factors, Aged, Aged, 80 and over, Aging, Chemotaxis, Leukocyte, Cross-Sectional Studies, Enzyme Activation, Humans, Immune System Diseases, Leukocyte Disorders, Middle Aged, Neutrophils, Signal Transduction, Cell Degranulation, Cytokines, Interleukin-8, Receptors, Cytokine, Phosphatidylinositol 3-Kinases, Myeloblastin, Young Adult
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