Every time cells divide, chromosomes get a little bit shorter. That’s why cells have telomeres—non-coding sequences of DNA that sit at the ends of chromosomes and protect genes from damage. Are telomeres involved in aging? Find out here.
What is Telomerase?
Telomeres are sequences of DNA at the ends of each chromosome. They don’t code for anything; instead, their job is to protect DNA from damage while it’s being copied. Each time cells divide, DNA duplicates, and telomeres get shorter .
When telomeres are too short to protect DNA, cells enter a state called senescence: they stop dividing. Ultimately, if these cells trigger the DNA damage response (DDR), they will be tagged for death [1, 2].
Telomerase is an enzyme that adds more nucleotides to the end of the telomere, elongating them. This allows cells to divide and grow for longer .
What is the CST Complex?
The CST complex is a structure that helps to protect your chromosomes from damage. CST doesn’t stand for a longer name; instead, it’s an abbreviation of the three proteins making up the complex: CTC1, STN1, and TEN1 [3, 4].
The CST complex is what’s called “evolutionarily conserved,” meaning that it’s almost identical across species as distantly related as yeast and humans. When a single gene, protein, or protein complex is common to that many species, researchers know it’s important .
But what does it do? The CST complex appears to have two major functions:
- Physically protecting telomeres (and the rest of the chromosome) from damage 
- Regulating the telomerase enzyme by both supporting its function & putting a limit on how often it can bind to DNA [5, 3]
CST in Humans
Of these, shelterin is considered more important; it is the major obstacle protecting your telomeres from damage. However, if certain components of shelterin (POT1 and TPP1) are missing or reduced, the CST complex is there to pick up the slack [3, 6].
Recent research has also shown that the CST complex helps your cells safely lengthen your telomeres during cell division. Thus, if any single protein in the CST complex isn’t functioning well, your telomeres could get dangerously short, resulting in premature aging .
Telomeres and the Science of Aging
Researchers have long suspected that shortening telomeres are among the causes of aging.
In adult tissues, there isn’t enough telomerase to keep up with cell division. Gradually, throughout our lifespans, our telomeres get shorter and shorter, and more and more of our cells enter senescence. Thus, older people can’t grow and regenerate their tissues as effectively as younger people [1, 2].
Short telomeres have also been linked with degenerative diseases and premature aging in humans. In this light, many researchers have attempted to discover whether activating telomerase and elongating telomeres can prevent or delay aging in humans and animals [1, 2, 7].
Gene Therapy for Mice
Telomere extension has already worked as an anti-aging strategy in animal models.
In one memorable study, middle-aged and older mice (one and two years old) were treated with gene therapy that increased their TERT expression. Those that received the treatment lived for 13-24% longer than those without. Best of all? There were no apparent side effects of the procedure .
How Much Telomerase is Best?
Given what we’ve just discussed, you might think that the answer is simple: the more active your telomerase (and the longer your telomeres), the better. However, there is no scientific consensus on the ideal range of telomerase activity or the ideal telomere length .
Too Much of a Good Thing?
Telomere length is a strange and controversial field of research, and long telomeres seem to have positive and negative effects, depending on the study and the frame of reference. Most notably, dangerous cancer cells tend to have high telomerase activity and unusually long telomeres [8, 1].
Some genetic variants, like rs2736100, are especially confusing. The homozygous ‘AA’ genotype, which reduces telomerase activity, is linked with testicular cancer and progressive scarring of the lungs [9, 10].
In this variant, the ‘C’ allele seems to increase telomerase activity and lengthen the telomeres, so you would think it would increase longevity. However, people with even one copy of the ‘C’ allele have a roughly 60% higher risk of developing glioma, a type of dangerous brain cancer, than those who don’t [9, 10].
Possible Interactions in Cancer Cells
To recap: many variants that increase TERT activity also increase cancer risk, but gene therapy to increase TERT in mice doesn’t cause cancer. Why this discrepancy? Researchers haven’t yet reached a consensus, but there are a few possible answers.
One possibility is that TERT doesn’t itself increase cancer risk, but instead amplifies the effect of other genes and mutations that do by allowing unlimited cell proliferation the tumor cells. A hallmark of cancer cells is that they can divide and proliferate indefinitely, and TERT mutations are probably the most likely mechanism behind this [11, 1].
TERT variants may also have other effects on tumor cells and future studies will be needed to fully understand their role in cancer.