Dorota Skowronska-Krawczyk
Department of Physiology & Biophysics
Department of Ophthalmology
University of California, Irvine

Role of aging in shaping cell structure and function

Biological age is one of the most relevant clinical traits in predicting disease risk, as well as mental and physical performance decline, including the loss of vision. The molecular link between age and vision decline is still not fully understood. Epigenetic aging of tissues and organs has been tightly correlated with changes in levels of DNA methylation, leading to the discovery of reliable biomarkers of aging. One of the top biomarkers is the level of methylation in the regulatory region of ELOVL2 (Elongation of Very Long Chain Fatty Acids-Like 2), encoding a key enzyme in the biosynthesis of docosahexaenoic acid (DHA) and n-3 and n-6 long-chain polyunsaturated fatty acids (LC-PUFAs).

Recently, we demonstrated that the lack of ELOVL2 enzymatic activity (Elovl2C234W) lowers levels of DHA and precursors of VLC-PUFAs in the mouse retina and liver. This decrease correlates with accelerated aging phenotypes, such as vision decline and the development of sub-retinal pigmented epithelium (RPE) deposits containing components of lipofuscin. Since Elovl2 expression in the retina decreases with age, our data demonstrate the causative role of the age-related DNA methylation biomarker and also provide a critical link between ELOVL2 enzymatic activity and age-related loss of vision. I will present our most recent data, which investigates the functional role of ELOVL2 in retinal pigment epithelium (RPE) cells. I will show our work on how changes in cell membrane lipid composition affect RPE function and discuss the important role of maintaining cell membrane integrity to preserve cell health and prevent organ aging.