Telomere Attrition and Aging


Telomeres are protective structures with DNA protein complexes at the ends of chromosomes, they consist of DNA bases that are repetitive. Telomeres prevent loss of genome integrity by maintaining chromosomal stability. Chromosomes are susceptible to DNA damage and degradation as well as abnormal interactions with other chromosomes; hence the need for protective caps at their ends. Telomere attrition is considered as a biomarker of aging. The shorter the telomere the higher the risk of developing age-related pathologies as well as aging prematurely. The enzyme telomerase inhibits telomere attrition. Telomerase maintains the tandem repeats by adding nucleotide sequences preventing the shortening of the telomeres. however telomerase translation activity declines with age.

telomere shortening In vivo studies in mice have shown that telomerase slows aging. Mice manipulated to be telomerase deficient aged prematurely but they recovered once the enzyme was restored; however, there are fears that telomerase use in humans could induce uncontrolled proliferation of cells and tumorigenesis. Age-related pathologies have been linked with telomere shortening as a result of the downregulation of telomerase expression. Telomere attrition exposes chromosomal DNA to reactive oxygen species and free radicals resulting in DNA damage and pathogenesis of disorders brought about by DNA damage, abnormal recombination, and aberrant chromosomal interaction. Pathogenesis of diseases such as osteoporosis, osteoarthritis, bone marrow failure, dyskeratosis congenita, acquired aplastic anemia, pulmonary fibrosis, liver disease, and cardiac disease have been connected to telomere erosion.

Telomere attrition suppresses cell proliferation and induces cellular senescence. Studies have shown that telomere shortening in bone tissue inhibits cell division and cellular function while its prolongation and maintenance prevents cellular senescence in osteosarcoma cells. Loss of telomere maintenance is therefore linked with the pathogenesis of musculoskeletal disorders such as osteoporosis, osteoarthritis, and osteosarcoma. Telomerase production declines with age hence the susceptibility of the elderly to musculoskeletal maladies.

Increased telomere erosion as a result of telomerase deficiency in organs such as the liver, lymphoid organs, and lungs inhibits tissue regeneration and promotes cellular senescence and cell death giving rise to the pathogenesis of liver cirrhosis in the liver, bone marrow failure in the lymphoid organs, pulmonary fibrosis in the lungs and acute myocardial infarction in the heart. Telomere attrition is common among the elderly, hence the vulnerability of the old to these disorders.

References

  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370421/
  • https://pubmed.ncbi.nlm.nih.gov/30779012/
  • https://www.nature.com/articles/news.2010.635
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401586/
  • https://journals.sagepub.com/doi/pdf/10.1177/147323001204000403