Human Telomerase Reverse Transcriptase, or hTERT, is a protein with broad implications for cellular processes. It is a core component that influences the lifespan and division capabilities of human cells.
The Core Function of hTERT
Chromosomes have protective caps at their ends called telomeres. These telomeres are made of repetitive DNA sequences, typically 5′-TTAGGG-3′, that prevent the loss of genetic material during DNA replication and cell division. Each time a cell divides, a small portion of these telomeric sequences is lost.
To counteract this shortening, cells employ an enzyme called telomerase. Telomerase is a ribonucleoprotein complex that maintains telomere length by adding new DNA sequences to chromosome ends. The hTERT protein is the catalytic subunit of this telomerase enzyme, which performs the actual synthesis of new telomeric DNA. This process involves hTERT using an RNA template component of telomerase to add the TTAGGG repeats.
hTERT and Cellular Aging
In most normal human somatic cells, hTERT activity is low or absent. This limited activity means that with each round of cell division, telomeres progressively shorten. This continuous shortening acts as a “mitotic clock,” signaling the cell’s age and limiting its replicative potential.
When telomeres reach a short length, the cell typically enters a state called cellular senescence, a stable arrest of cell division, or undergoes apoptosis, programmed cell death. This regulated inactivity of hTERT in normal cells is a natural part of the aging process. It also serves as a protective mechanism, preventing cells from dividing indefinitely and developing into uncontrolled growths.
hTERT’s Connection to Cancer
In contrast to normal somatic cells, most cancer cells exhibit reactivation or upregulation of hTERT activity. This allows them to maintain telomere length, bypassing normal cellular aging checkpoints that limit division. By sustaining telomere length indefinitely, cancer cells gain “immortality,” a characteristic important for their uncontrolled proliferation and tumor formation.
The sustained activity of hTERT in cancer cells enables them to divide indefinitely, unlike healthy cells with a finite lifespan. This makes hTERT reactivation a recognized hallmark of many human cancers, contributing to their unchecked growth and spread. Approximately 90% of human cancers show upregulated telomerase activity, primarily due to increased hTERT expression.
Harnessing hTERT for Health
Understanding hTERT’s role opens avenues for therapeutic strategies. In cancer therapy, inhibiting hTERT activity is a promising approach aimed at forcing cancer cells into senescence or apoptosis by allowing telomeres to shorten. For instance, some experimental compounds can bind to and stabilize the telomeric structure, preventing telomerase from replicating telomeres.
Conversely, in anti-aging and regenerative medicine, researchers are exploring transiently modulating hTERT activity to combat age-related diseases or enhance the body’s regenerative capacity. While activating hTERT could theoretically extend the lifespan of healthy cells and tissues, such interventions carry complexities and risks, including increased cancer risk if not carefully controlled.