Telomere and its role in the aging pathways: telomere shortening, cell senescence and mitochondria dysfunction

Abstract

Aging is a biological process characterized by a progressive functional decline in tissues and organs, which eventually leads to mortality. Telomeres, the repetitive DNA repeat sequences at the end of linear eukaryotic chromosomes protecting chromosome ends from degradation and illegitimate recombination, play a crucial role in cell fate and aging. Due to the mechanism of replication, telomeres shorten as cells proliferate, which consequently contributes to cellular senescence and mitochondrial dysfunction. Cells are the basic unit of organismal structure and function, and mitochondria are the powerhouse and metabolic center of cells. Therefore, cellular senescence and mitochondrial dysfunction would result in tissue or organ degeneration and dysfunction followed by somatic aging through multiple pathways. In this review, we summarized the main mechanisms of cellular senescence, mitochondrial malfunction and aging triggered by telomere attrition. Understanding the molecular mechanisms involved in the aging process may elicit new strategies for improving health and extending lifespan.

<p>Shelterin Complex at Telomeres: Implications in Ageing</p>

“…55 Indeed, when the length of telomeres becomes critically short, the secondary protective structure does not occur; thus the cells enter replicative senescence. 13 Meanwhile, shelterin complex can act as a critical regulator for the activity of telomerase. It serves as a negative regulator of telomerase since it is attached to telomeres in a manner dependent on their length (Table 1).…”

Senescence and Inflammatory Markers for Predicting Clinical Progression in Parkinson’s Disease: The ICICLE-PD Study

“…Telomeres are protective structures at chromosomal ends. Telomere shortening and dysfunction cause cellular senescence [8]. Importantly, telomeres are susceptible to oxidative stress [9] and can be indicators of ongoing disease processes in the brain.…”

Myocardial Cell Aging in the Elderly

“…When the shortening reaches a critical length, chromosomes lose their stability and mitochondrion dysfunction occurs. Cells no longer divide and become aged, which damages the repair function of tissues and organs, resulting in abnormal structures and functions in cells and tissues [7]. Van der Hart et al [8] found that the telomere length of leukocytes in patients with congestive heart failure was shorter than that of the control group without the disease.…”