Whether we like it or not, we’re faced with many physical changes as we get older. Wrinkles form, bones and muscles grow weaker… even the way fat is distributed throughout the body changes radically. As we age, we lose a certain type of fat cell that burns fatty deposits, which increases the risk for obesity. But there may be hope. Interestingly, researchers are finding that an epigenetic enzyme might be able to prevent this pesky change from happening.
Epigenetics has significant influence on aging and may even destine some to age faster regardless of lifestyle. Previous research has shown that epigenetic histone modifications could play an essential role in determining how long we live. Understanding molecular mechanisms such as histone modifications could bring us closer to the widespread hope of putting a hold on getting old.
Beige fat cells, which can burn fatty deposits through thermogenesis, actually turn into white fat cells as we age. These adipocytes are unable to burn fat, which increases our risk of developing obesity. But what if an epigenetic enzyme could control this process?
Researchers from Germany discovered that lysine specific demethylase 1 (Lsd1), a well-known epigenetic enzyme, plays an important role in fat cell transformation. When Lsd1 levels decrease in fat tissue as we get older, the number of beige adipocytes is reduced.
In a mouse study, the group maintained the level of Lsd1 in mice as they age at just about the same level found in young mice. Increased Lsd1 expression in older mice reduced age-related transition of fat-burning beige adipocytes to white adipocytes. Additionally, they found that loss of Lsd1 early on actually sped up the process of fat cell transformation.
Specifically, the researchers discovered that Lsd1 maintains beige adipocytes by controlling the expression of a gene known as peroxisome proliferator-activated receptor α (Ppara). They were able to manipulate the process and conserve beige fat cells.
“Treatment with a [PPAR-alpha] agonist is sufficient to rescue the loss of beige adipocytes caused by Lsd1 ablation,” they reported. Interestingly, this gene has potential as a therapeutic target due to how easily drugs can activate or suppress it.
Lsd1 was the first identified histone demethylase and it plays an important role in countless cellular processes. This and other epigenetic enzymes erase histone methylation marks, which impact the structure of chromatin and therefore change gene expression. The discovery of histone demethylases demonstrates that histone methylation is not a permanent modification, but rather a dynamic process that could impact different activities in the body.
Their results demonstrate the possibility of intervening in the beige-to-white adipocytes transition, which could help reduce the chance of becoming obese as we age. More and more, epigenetics is revealing its role in aging and bringing to light the possible ways in which we might be able to exert a little more control over getting old.
Source: Duteil, D. et al. (2017). Lsd1 prevents age-programed loss of beige adipocytes. PNAS. Early edition.
Reference: Albert-Ludwigs-Universität Freiburg. Improving Control of Age-Related Obesity. Public Relations. 04 May 17. Web.