Overactive Protein Acetylation Connected To The Aging Process

Credit: NASA / Dominic Hart

Age-dependent genetic and metabolic changes in middle aged fruitflies have been linked to a process called protein acetylation, which becomes more active with age  

What is protein acetylation?

Your proteins undergo all sorts of modifications to alter their activity, and one such modification is acetylation. This involves transferring an acetyl group, CH3CO,  particularly onto lysine residues on a protein. Acetylation not only affects the activity of a protein, but it also plays a big role in epigenetics – the regulation of your gene expression. Acetylation affects histone proteins, which your DNA is packed around in the nucleus, and controls gene expression.

Enzymes like HAT, histone acetyl transferase, add acetyl groups to histones which loosens chromatin structure and changes gene expression

What’s new?

New research discovered that in middle aged flies, a mere 7 weeks old, oxygen consumption was increased compared to young flies. After analysing this further they found that mitochondria activity was increased alongside a rise in a molecule called acetyl-CoA which is an essential metabolite and a source of acetyl groups. This increase in acetyl-CoA coincided with a rise in protein acetylation too.

“Acetyl groups are attached to specific positions in certain proteins by dedicated enzymes, and can be removed by a separate set of enzymes. These modifications modulate the functions of the proteins to which they are added, and our experiments have shown that many proteins are much more likely to be found in acetylated form in middle-aged flies than in younger individuals”

Acetyl-CoA

This increase in protein acetylation not only impacts on metabolism, but on gene expression too.

“We were able to show that the histones in middle-aged flies are overacetylated. This reduces the packing density of the DNA, and with it the stringency of gene regulation. The overall result is a rise in the level of errors in the expression of the genetic information, because genetic material that should be maintained in a repressed state can now be reactivated. In the prime of their lives, fruitflies begin to produce a surfeit of acetylated proteins, which turns out to be too much of a good thing”

Reversing these changes was beneficial

After establishing this age-related change, the researchers inhibited acetyl-CoA formation and an enzyme that transfer acetyl groups, and found that this reversed these modification patterns, and improved health and longevity in these fruit flies. This raises the possibility of targeting these enzymes one day in humans if we are found to exhibit similar changes, to lessen or reverse harmful acetylation.

Read more at Phys.org