Age- and sex- divergent translatomic responses of the mouse retinal pigmented epithelium.
Neurobiol Aging
; 140: 41-59, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38723422
ABSTRACT
Aging is the main risk factor for age-related macular degeneration (AMD), a retinal neurodegenerative disease that leads to irreversible blindness, particularly in people over 60 years old. Retinal pigmented epithelium (RPE) atrophy is an AMD hallmark. Genome-wide chromatin accessibility, DNA methylation, and gene expression studies of AMD and control RPE demonstrate epigenomic/transcriptomic changes occur during AMD onset and progression. However, mechanisms by which molecular alterations of normal aging impair RPE function and contribute to AMD pathogenesis are unclear. Here, we specifically interrogate the RPE translatome with advanced age and across sexes in a novel RPE reporter mouse model. We find differential age- and sex- associated transcript expression with overrepresentation of pathways related to inflammation in the RPE. Concordant with impaired RPE function, the phenotypic changes in the aged translatome suggest that aged RPE becomes immunologically active, in both males and females, with some sex-specific signatures, which supports the need for sex representation for in vivo studies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aging
/
Sex Characteristics
/
Retinal Pigment Epithelium
/
Macular Degeneration
Limits:
Animals
Language:
En
Journal:
Neurobiol Aging
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos