Aging hampers neutrophil extracellular traps (NETs) efficacy

Area of Science:

• Immunology
• Cell Biology
• Aging Research

Background:

• NETosis is a crucial neutrophil defense mechanism involving the release of neutrophil extracellular traps (NETs) to trap and kill pathogens.
• NETosis function is known to be impaired in both aging mice and humans.

Purpose of the Study:

• To investigate the functional differences in NETs produced by elderly (>65 years) versus adult (20-50 years) individuals.
• To compare the efficacy of NETs from these groups in inhibiting Staphylococcus aureus growth and stimulating keratinocyte proliferation.

Main Methods:

• Neutrophils from healthy elderly and adult subjects were stimulated to form NETs.
• NET production was quantified, and the antimicrobial activity of NETs against S. aureus was assessed.
• The effect of NETs on keratinocyte (HaCaT cells) proliferation was evaluated, and NET DNA size was analyzed via flow cytometry.

Main Results:

• Elderly subjects exhibited greater NET production compared to adults.
• However, NETs from elderly individuals demonstrated reduced bactericidal capacity and lower stimulation of keratinocyte proliferation.
• Analysis revealed that NETs from elderly subjects had larger DNA sizes compared to those from adults.

Conclusions:

• Aging is associated with structural modifications in NETs, leading to decreased antimicrobial activity and keratinocyte proliferation stimulation.
• The larger DNA size of NETs in elderly individuals is a novel finding and may contribute to age-related pathogenic mechanisms.