Academy

Understanding Telomeres and Their Role in Aging

Telomeres are repetitive DNA sequences found at the ends of chromosomes that protect the genetic code during cell division. Each time a cell divides, its telomeres shorten slightly. Over time, this shortening reaches a critical point where the cell can no longer divide, entering a state called replicative senescence.

Maintaining telomere length is crucial for cell health and longevity. Two key factors regulate telomeres:

1. Telomerase Enzyme: Adds back telomeric repeats to chromosome ends. High telomerase activity in stem cells and germline cells supports extended division, while most adult cells have low telomerase activity, leading to gradual shortening.
2. Shelterin Complex: A group of proteins that binds telomeres and shields them from DNA damage responses, preserving genomic stability.
   1. TRF1 and TRF2 bind directly to telomeric repeats.
   2. POT1, TIN2, TPP1, and RAP1 form additional protective interactions.

Why Telomeres Matter in Longevity Science:

• Telomere shortening is a biomarker of cellular aging and organismal healthspan.
• Dysfunctional telomeres can cause DNA damage responses that lead to senescence or cancerous growth.
• Therapeutic approaches aim to modulate telomerase activity or enhance shelterin stability.

Future Directions: Research focuses on developing safe telomerase activators, gene therapies targeting shelterin components, and lifestyle interventions (e.g., stress reduction, nutrition) that may influence telomere biology. Understanding telomere dynamics opens new avenues for delaying aging-related diseases and extending healthy lifespan.