例如:"lncRNA", "apoptosis", "WRKY"

The lipid elongation enzyme ELOVL2 is a molecular regulator of aging in the retina.

Aging Cell. 2020 Feb;19(2):e13100. doi:10.1111/acel.13100. Epub 2020 Jan 14
Daniel Chen 1 , Daniel L Chao 1 , Lorena Rocha 1 , Matthew Kolar 2 , Viet Anh Nguyen Huu 1 , Michal Krawczyk 1 , Manish Dasyani 1 , Tina Wang 3 , Maryam Jafari 1 , Mary Jabari 1 , Kevin D Ross 4 , Alan Saghatelian 2 , Bruce A Hamilton 5 , Kang Zhang 1 , Dorota Skowronska-Krawczyk 6
Daniel Chen 1 , Daniel L Chao 1 , Lorena Rocha 1 , Matthew Kolar 2 , Viet Anh Nguyen Huu 1 , Michal Krawczyk 1 , Manish Dasyani 1 , Tina Wang 3 , Maryam Jafari 1 , Mary Jabari 1 , Kevin D Ross 4 , Alan Saghatelian 2 , Bruce A Hamilton 5 , Kang Zhang 1 , Dorota Skowronska-Krawczyk 6
+ et al

[No authors listed]

Author information
  • 1 Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, USA.
  • 2 The Salk Institute for Biological Studies, Clayton Foundation Laboratories for Peptide Biology, La Jolla, CA, USA.
  • 3 Department of Medicine, University of California San Diego, La Jolla, CA, USA.
  • 4 Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
  • 5 Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
  • 6 Atkinson Laboratory for Regenerative Medicine, University of California San Diego, La Jolla, CA, USA.

摘要


Methylation of the regulatory region of the elongation of very-long-chain fatty acids-like 2 (ELOVL2) gene, an enzyme involved in elongation of long-chain polyunsaturated fatty acids, is one of the most robust biomarkers of human age, but the critical question of whether ELOVL2 plays a functional role in molecular aging has not been resolved. Here, we report that Elovl2 regulates age-associated functional and anatomical aging in vivo, focusing on mouse retina, with direct relevance to age-related eye diseases. We show that an age-related decrease in Elovl2 expression is associated with increased DNA methylation of its promoter. Reversal of Elovl2 promoter hypermethylation in vivo through intravitreal injection of 5-Aza-2'-deoxycytidine (5-Aza-dc) leads to increased Elovl2 expression and rescue of age-related decline in visual function. Mice carrying a point mutation C234W that disrupts Elovl2-specific enzymatic activity show electrophysiological characteristics of premature visual decline, as well as early appearance of autofluorescent deposits, well-established markers of aging in the mouse retina. Finally, we find deposits underneath the retinal pigment epithelium in Elovl2 mutant mice, containing components found in human drusen, a pathologic hallmark of age related macular degeneration. These findings indicate that ELOVL2 activity regulates aging in mouse retina, provide a molecular link between polyunsaturated fatty acids elongation and visual function, and suggest novel therapeutic strategies for the treatment of age-related eye diseases.

KEYWORDS: DNA methylation, ELOVL2, PUFA, age-related macular degeneration, aging, retina