Special Issue Information

Aging is defined biologically as a progressive and inexorable failure of homeostasis leading to an increased susceptibility to develop many diseases. At the mechanistic level, aging is widely understood to result from limitations in somatic maintenance associated with accumulation of DNA and macromolecular damage, telomere attrition, cellular senescence and inflammation, and stem cell depletion. These changes can be further accompanied by dysregulated nutrient sensing, metabolic and epigenetic alterations, loss of proteostasis and autophagic function, impaired intercellular communication, and a decline in immune competence. Despite these insights, little is known about the temporal dynamics that govern the emergence, intensity, tissue specificity, and downstream consequences of these aging hallmarks. There is growing evidence that aging-related mechanisms may play a significant role in the initiation of carcinogenesis and the progression of tumors. Among these mechanisms, the role of telomere dysfunction and telomerase modulation in aging and cancer has evolved in recent years. Numerous recent studies have shown that telomerase activation or ectopic expression of its catalytic subunit, telomerase reverse transcriptase (TERT), can counteract aging-related processes. One current example for anti-aging treatments are the so-called telomerase activators which in cells such as lymphocytes where telomerase can get activated, are able to extend either all telomeres (median telomere length) or just the shortest telomeres preventing them from emanating damage signals. Beyond its role in telomere maintenance, TERT also exerts non-canonical functions that can activate diverse cellular processes that counteract aging and neurodegenerative diseases but also promote cancer.

The special edition “Genomic Instability and Telomeres in Aging and Cancer” aims to feature research articles and insightful reviews that either explore the links between genomic instability and various hallmarks of aging or highlight recent advances in telomere and telomerase biology within the context of aging and cancer.

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