Scientists investigate telomere restoration as an aging invention

Researchers are probing mechanisms to reverse telomere shortening as an intervention to alleviate aging-related decline. The term telomeres is derived from the Greek word ‘telos’ (meaning ‘end’) and ‘meros’ (meaning ‘part’). These are DNA-protein structures that are found at the ends of chromosomes. Telomeres play a similar role as the plastic ‘caps’ at the ends of your shoelaces. They stop the ends of chromosomes from sticking to each other, thus maintaining chromosome stability and ensuring that DNA gets copied properly when cells divide. Scientists have, for a long time, known that telomeres get shorter each time a cell divides due to what is referred to as the end replication problem (the DNA at the very end of each chromosome cannot be fully copied in each round of replication). This progressive shortening eventually causes the cell to stop functioning property — particularly if genes that are important for its survival are lost. This results in a negative impact on the health and lifespan of an individual. Studies involving mice have shown that age-dependent telomere shortening (and the accompanying genetic instability) result in a limited capacity to cope with injury, reduced regenerative potential of different cells, and a shortened lifespan. Since telomeres are important in maintaining chromosome stability and healthy cell function, cells stop dividing and enter senescence (loss of ability to divide and grow) when telomere length reaches a certain minimum limit. This is referred to as the Hayflick limit after Leonard Hayflick, the anatomist who discovered that cells stop dividing after 50 replications. Beyond this limit, telomeres have already lost their structural integrity. Any cell that continues to divide will reach a crisis stage where it either dies or spirals into uncontrolled growth that could result in tumors. Scientists have looked at how — among other anti-aging interventions — the continuous shortening of telomeres could be arrested and reverted to promote positive outcomes for health and lifespan. In 2009, researchers Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak won the Nobel Prize in Medicine or Physiology for their discovery of the enzyme telomerase. The trio established that telomerase can actually extend telomeres and protect them from shortening over time. This discovery opened the door for intensified research on potential interventions to reactive shortened telomeres. Recent mice studies have demonstrated that reactivation of telomerase reduces DNA damage, restores healthy growth, and reverses degeneration in multiple organs including the spleens, testes, and intestines. There’s also been similar evidence in human studies investigating patients with telomeropathies. These are conditions such as liver cirrhosis, pulmonary fibrosis, kidney disease, and bone marrow failure that have been linked to gene mutations as a result of telomere shortening. Scientists are now experimenting with a variety of telomerase activators ranging from small molecules to hormonal factors, mRNA, to gene therapy. While most of the ongoing therapeutic approaches have been largely promising, there’s the question of safety as reactivating telomeres in rogue cells could result in increased cancer risk. Some researchers have recommended transient telomerase induction as a way to overcome safety risks. Still, more work needs to be done to fill knowledge gaps and understand potential risks before feasible telomere restoration therapies can be realized.