Although most of us accept aging as a natural part of life, it might not have to be. Researchers at UC Berkeley have now mapped out the structure of telomerase – an enzyme known to play a key role in aging and cancer – in more detail than ever before, and the breakthrough could inform a new generation of highly-targeted drugs.
The physical decline we associate with aging can be largely traced back to one little thing in your body: telomeres. These short sequences of DNA form protective caps on the tips of each chromosome, making sure that no important information is lost when the cell divides. Unfortunately, they can't keep that up forever, eventually wearing down to the point where crucial DNA degrades, slowly giving us wrinkled skin, slower metabolisms, weaker organs, and higher chances of disease.
Telomeres aren't alone in fighting aging, though. They have backup in the form of an enzyme known as telomerase, which tries to delay the decline as long as possible by replenishing the telomeres. Plenty of anti-aging research has focused on telomerase, be it experimenting with boosting its levels via injection, supercharging its function or manipulating its natural "off" switch.
In order to really take advantage of telomerase, scientists have been studying this complex enzyme in more detail to better understand its structure. It's made up of an RNA backbone decorated by six kinds of protein, which all move around while they replenish telomeres. But it was hard to pin down how it all fit together, how many proteins are at work there, and how they perform that function.
So the UC Berkeley team isolated telomerase, purified it, and examined it using a state-of-the-art cryoelectron microscope. This instrument uses an electron beam as a light source to study a sample cooled to cryogenic temperatures, and allowed researchers to peer closer than ever before.
"The best previous images of human telomerase had a resolution of only 30 Ångstroms (3 nanometers); we were able to get about 7 to 8 Ångstroms (0.7 to 0.8 nm) resolution using cryoelectron microscopy," says Thi Hoang Duong Nguyen, first author of the study. "When I got to the point where I could see all the subunits – we had 11 protein subunits in total – it was a moment of, 'Wow, wow, this is how they all fit together.'"
According to the team, these high-resolution images, along with our current understanding of the telomerase gene sequence, is enough to start thinking about potential drug targets related to the enzyme. Finding ways to increase the activity of telomerase, for example, could help stave off the negative effects of aging for longer, while blocking its function could help fight cancer, which often hijacks telomerase to make its own cells essentially "immortal."
To improve that understanding, the next step for the researchers is to further boost the resolution of the images to about 3 or 4 Ångstroms. The team describes the work in the video below.
The research was published in the journal Nature.
Source: UC Berkeley
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