Source: Thailand Medical News Jan 17, 2020 4 years, 11 months, 6 days, 5 hours, 23 minutes ago
A gene called Elongation of Very Long Chain Fatty Acids Protein 2 or
ELOVL2 is an established
biomarker of
age and in a new study has been identified to play a critical role in
eye aging and the
retina. In a new paper, published in the journal
Aging Cell, researchers at University of California San Diego School of Medicine say the gene appears to play a key role in
age-associated functional and anatomical
aging in vivo in mouse
retinas, a finding that has direct relevance to age-related
eye diseases.
The research team, led by senior author Dr Dorota Skowronska-Krawczyk, Ph.D., Assistant Professor in the Viterbi Family Department of Ophthalmology at UC San Diego Shiley
Eye Institute, found that an
age-related decrease in
ELOVL2 gene expression was associated with increased DNA methylation of its promoter. Methylation is a simple biochemical process in which groups of carbon and hydrogen atoms are transferred from one substance to another. In the case of DNA, methylation of regulatory regions negatively impacts expression of the gene.
When the medical researchers reversed hypermethylation
in vivo, they boosted
ELOVL2 expression and rescued age-related decline in visual function in mice. "These findings indicate that
ELOVL2 actively regulates
aging in mouse
retina, provides a molecular link between polyunsaturated fatty acids elongation and visual functions, and suggests novel therapeutic strategies for treatment of
age-related eye diseases," wrote the authors.
Typically,
ELOVL2 is involved in production of long-chain omega-3 and omega-6 polyunsaturated fatty acids, which are used in several crucial biological functions, such as energy production, inflammation response and maintenance of cell membrane integrity. The gene is found in humans as well as mice.
Most significantly,
ELOVL2 regulates levels of docosahexaenoic acid or DHA, a polyunsaturated omega-3 fatty acid abundantly found in the brain and
retina. DHA is associated with a number of beneficial effects. Notably, its presence in photoreceptors in
eyes promotes healthy
retinal function, protects against damage from bright light or oxidative stress and has been linked to improving a variety of vision conditions, from
age-related macular (
AMD)
degeneration to diabetic
eye disease and
dry eyes.
Dr Skowronska-Krawczyk told
Thailand Medical News, “The research work demonstrated for the first time that a ‘methylation clock’ gene had a functional role in the
aging
strong>of an organ. In this case, the eye. DNA methylation is used throughout the human body, essentially turning biological switches on an off to maximize efficient operation. It has key regulatory roles in the body's cardiovascular, neurological, reproductive and detoxification systems.”
Recently, there has been much work and progress in identifying possible biomarkers that predict the biological age (not chronological) of individuals. Such biomarkers would be useful in identifying risk and status of age-related diseases. ELOVL2 is among the genes attracting greatest interest.
Dr Skowronska-Krawczyk added, "I have been asked whether I think ELOVL2 is the aging gene. After thinking about it, it is not unreasonable to think that lower ELOVL2 expression might be at the basis for many age-related conditions. Future work in our lab will address that question."
Reference : Daniel Chen et al, The lipid elongation enzyme ELOVL2 is a molecular regulator of aging in the retina, Aging Cell (2020). DOI: 10.1111/acel.13100
