Telomeres, the protective caps at the ends of chromosomes, shorten with each cell division, contributing to aging and age-related diseases. This review explores the role of telomeres in aging and strategies to target telomere shortening for healthy aging and longevity. Telomere attrition is a key hallmark of aging, and research focuses on therapies to counteract it, such as telomerase activators and tankyrase inhibitors. Telomerase, an enzyme that extends telomeres, is crucial for cellular health, while tankyrase inhibitors regulate telomere maintenance through the Wnt signaling pathway. Antioxidants and anti-inflammatory agents also play a role in preserving telomere length by reducing oxidative stress and inflammation. Studies on telomere-targeting interventions, including telomerase activators like TA-65 and Cycloastragenol, show potential in delaying aging and improving healthspan. However, risks such as cancer promotion must be carefully managed. Additionally, statins and spermidine have shown promise in modulating telomere biology through anti-inflammatory and autophagy mechanisms. Despite these advances, further research is needed to validate these interventions in humans and ensure their safety and efficacy. Understanding telomere biology is essential for developing effective strategies to combat aging and age-related diseases.Telomeres, the protective caps at the ends of chromosomes, shorten with each cell division, contributing to aging and age-related diseases. This review explores the role of telomeres in aging and strategies to target telomere shortening for healthy aging and longevity. Telomere attrition is a key hallmark of aging, and research focuses on therapies to counteract it, such as telomerase activators and tankyrase inhibitors. Telomerase, an enzyme that extends telomeres, is crucial for cellular health, while tankyrase inhibitors regulate telomere maintenance through the Wnt signaling pathway. Antioxidants and anti-inflammatory agents also play a role in preserving telomere length by reducing oxidative stress and inflammation. Studies on telomere-targeting interventions, including telomerase activators like TA-65 and Cycloastragenol, show potential in delaying aging and improving healthspan. However, risks such as cancer promotion must be carefully managed. Additionally, statins and spermidine have shown promise in modulating telomere biology through anti-inflammatory and autophagy mechanisms. Despite these advances, further research is needed to validate these interventions in humans and ensure their safety and efficacy. Understanding telomere biology is essential for developing effective strategies to combat aging and age-related diseases.