Aging hampers neutrophil extracellular traps (NETs) efficacy
Open accessAbstract
Background: NETosis is a neutrophil-mediated defense mechanism during which DNA and enzymes are extruded forming a network (NETs) trapping and killing different pathogens. NETosis is reduced in both mice and humans during aging. Aims: We explored the difference in the efficacy of NETs released in elderly (> 65 years) versus adults (20–50 years) subjects in inhibiting Staphylococcus aureus growth and activating the growth of keratinocytes. Methods: Neutrophil granulocytes, obtained from venous blood both in healthy elderly and adult subjects, were stimulated by LPS (0–250 µg/ml) to induce the formation of NET. NETs were quantified by SYBR Green staining and growth inhibition of S. aureus was evaluated by disk diffusion test. Furthermore, NETs (0–500 ng/ml) were added to immortalized human keratinocytes (HaCaT cells), and their proliferation was evaluated by MTT assay after 24 h. Finally, the DNA size of NETs was evaluated by flow cytometry after SYBR Green staining. Results: Greater production of NETs was observed in elderly subjects than in adults, but these NETs showed reduced bactericidal capacity and HaCaT cells’ proliferation stimulation. The activities of the NETs are related to the size of the extruded DNA threads, and when NETs size was analyzed, DNA from elderly showed a higher size compared to that obtained by adults. Discussion: Unexpected results showed aging-related NETs structural modification resulting in both a lower antimicrobial activity and keratinocyte proliferation stimulation compared to NETs obtained from adults. Conclusions: The NETs DNA size observed in elderly subjects has not been previously reported and could be part of other pathogenic mechanisms observed in aging.
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Senescent neutrophils have a reduced capacity to release NETs.
“Senescent neutrophils exhibit several distinct characteristics during NETosis, including a reduced capacity to release NETs, instability in the quality of formed NETs, and decreased activity of DNA degrading enzymes (DNases) within NETs.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [269]
The Results and Discussion report that neutrophils from elderly subjects produced more NETs than those from adults after LPS stimulation, contrary to the unqualified claim of reduced release. The Introduction and Discussion note reduced NET production in other studies using different stimulation conditions, but distinguish those findings from this paper’s results. (LLM, conf=0.87)
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Experimental — accuracy not yet measuredThe ability of neutrophils to undergo NETosis may be affected by aging.
“The ability of neutrophils to undergo NETosis may be affected by aging.269”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [269]
Senescent neutrophils have instability in the quality of formed NETs.
“Senescent neutrophils exhibit several distinct characteristics during NETosis, including a reduced capacity to release NETs, instability in the quality of formed NETs, and decreased activity of DNA degrading enzymes (DNases) within NETs.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [269]
Senescent neutrophils have decreased activity of DNA degrading enzymes (DNases) within NETs.
“Senescent neutrophils exhibit several distinct characteristics during NETosis, including a reduced capacity to release NETs, instability in the quality of formed NETs, and decreased activity of DNA degrading enzymes (DNases) within NETs.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [269]
The Discussion reports larger, less fragmented NET DNA in elderly subjects, but does not attribute that finding to decreased DNase activity. Its mention of DNase I deficiency concerns NET degradation in autoimmune diseases such as SLE, not senescent neutrophils. Searches for reduced DNase activity in elderly NETs found no supporting passage. (LLM, conf=0.76)
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Inflammation and aging: signaling pathways and intervention therapies
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“The ability of neutrophils to undergo NETosis may be affected by aging.(269) Senescent neutrophils exhibit several distinct characteristics during NETosis, including a reduced capacity to release NETs, instability in the quality of formed NETs, and decreased activity of DNA degrading enzymes (DNases) within NETs.”
BackgroundThe Impact of Immune System Aging on Infectious Diseases
Quiros-Roldan, E., Sottini, A., Natali, P. G., & Imberti, L. (2024) · Microorganisms · doi:10.3390/microorganisms12040775 · Cited by 133 · see citing works
- Authors
- Sabbatini, M., Bona, E., Novello, G., Migliario, M., & Renò, F.
- Affiliations
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- Corresponding author
- Renò, Filippo
- Venue
- Aging Clinical and Experimental Research
- Published
- 2022-08-03
- Volume
- 34
- Issue
- 10
- Pages
- 2345-2353
- ISSN
- 1594-0667 (ISSN-L)
- 1720-8319
- PMC
- PMC9637667
- OpenAlex
- W4289549992
- Cited by
- 51
- References
- 50
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 10 · 2023: 9 · 2022: 1
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Aging Clinical and Experimental Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Funders
- Università degli Studi del Piemonte Orientale Amedeo Avogrado
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- neutrophil extracellular traps, NETosis, aging, Staphylococcus aureus, bactericidal activity, keratinocyte proliferation, neutrophils, innate immunity
- MeSH terms
- Aged, Aging, Animals, Diamines, DNA, Humans, Neutrophils, Quinolines, Staphylococcus aureus, Mice, Benzothiazoles, Extracellular Traps
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