Carotid Body-Mediated Chemoreflex Function in Aging and the Role of Receptor-Interacting Protein Kinase.
Adv Exp Med Biol
; 1427: 195-201, 2023.
Article
em En
| MEDLINE
| ID: mdl-37322350
Ventilatory impairment during aging has been linked to carotid body (CB) dysfunction. Anatomical/morphological studies evidenced CB degeneration and reductions in the number of CB chemoreceptor cells during aging. The mechanism(s) related to CB degeneration in aging remains elusive. Programmed cell death encompasses both apoptosis and necroptosis. Interestingly, necroptosis can be driven by molecular pathways related to low-grade inflammation, one hallmark of the aging process. Accordingly, we hypothesized that necrotic cell death dependent on receptor-interacting protein kinase-3 (RIPK3) may contribute, at least in part, to impair CB function during aging. Adult (3 months) and aged (24 months) wild type (WT) and RIPK3-/- mice were used to study chemoreflex function. Aging results in significant reductions in both the hypoxic (HVR) and hypercapnic ventilatory responses (HCVR). Adult RIPK3-/- mice showed normal HVR and HCVR compared to adult WT mice. Remarkable, aged RIPK3-/- mice displayed no reductions in HVR nor in HCVR. Indeed, chemoreflex responses obtained in aged RIPK3-/- KO mice were undistinguishable from the ones obtained in adult WT mice. Lastly, we found high prevalence of breathing disorders during aging and this was absent in aged RIPK3-/- mice. Together our results support a role for RIPK3-mediated necroptosis in CB dysfunction during aging.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Corpo Carotídeo
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Adv Exp Med Biol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Estados Unidos