Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection

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Science  04 Dec 2015:
Vol. 350, Issue 6265, pp. 1193-1198
DOI: 10.1126/science.aab3389
  1. Fig. 1 Telomere structure.

    The human telomere complex consists of a chromosomal-terminal tract of a tandemly repeated DNA sequence bound by protective shelterin component proteins, with additional protective proteins on the overhanging single-stranded end region of the telomeric DNA repeat. This simplified schematic does not indicate details of the protein structures or of the architecture of the telomeric complex.

  2. Fig. 2 Long-term maintenance of telomeric DNA length requires telomerase.

    (A) Replication of telomeric DNA. Elongation of one DNA strand, via the reverse transcriptase mechanism of telomeric DNA synthesis by telomerase, is followed by synthesis of the other telomere DNA strand by DNA polymerase. (B) As cells divide, shortening of telomeres through incomplete DNA replication and other processes causing attrition can be balanced by compensatory telomere-elongating action by telomerase. (C) Net telomere shortening when telomerase is insufficient leads to critically short telomeres. Telomere damage signaling leads to cession of cell division and other cellular responses.

  3. Fig. 3 Different inputs to telomere maintenance have disease-specific consequences.

    Observed telomere length results from combined genetic and nongenetic inputs. Longer observed telomeres are associated with lower overall risks for mortality and diseases. The variants of telomere maintenance genes that promote longer telomeres decrease CAD and Alzheimer’s disease risks yet raise risks of specific cancer types and for combined all-cancers mortality. Nongenetic influences that lead to better telomere length maintenance are protective.

  4. Fig. 4 Relationship of telomere attrition to human aging-related diseases.

    Telomere attrition is depicted as an underlying, shared, interactive contributor to the etiologies of aging and aging-related diseases. Because both nongenetic and genetic influences affect it, telomere maintenance is a malleable and integrative indicator of overall health.

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