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. 2019 Jul 7;6(5):e1632613.
doi: 10.1080/23723556.2019.1632613. eCollection 2019.

Telomeres and sirtuins: at the end we meet again

Hisayuki Amano  1 , Ergun Sahin  2   3
Affiliations

Telomeres and sirtuins: at the end we meet again

Hisayuki Amano et al. Mol Cell Oncol. .

Abstract

Telomeres and sirtuins are independently implicated in causing disease and aging, but how they cooperate is not well understood. A recent study demonstrates that telomere shortening represses sirtuins and increasing sirtuin activity stabilizes telomeres and improves telomere-dependent disease, suggesting that these two pathways are tightly intertwined.

Keywords: NAD(+); Telomeres; aging; damage; disease; p53; sirtuins.

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Figures

Figure 1.
Figure 1.
Molecular pathways linking telomeres and p53 to sirtuins. Dysfunctional telomeres activate the DNA damage response and tumor protein p53 (TP53, known as p53). P53 regulates non-mitochondrial sirtuins Sirt1, 2, 6 & 7 through miRNA-34a, 26a & 145a while it regulates the mitochondrial sirtuins Sirt3, 4 & 5 at the transcriptional level through Peroxisome proliferator-activated receptor gamma coactivator 1-alpha and beta (PGC-1α/β). Increasing Nicotinamide adenine dinucleotide ((NAD(+)) levels through NAD(+) precursors increases sirtuin activity, stabilizes telomeres and dampens p53 in a partially Sirt1-dependent manner indicating the involvement of Sirt6 or other NAD(+) – dependent enzymes. The repression of Sirt1 in the setting of short telomeres contributes to PGC-1α impairment directly as Sirt1 is known to activate PGC-1α through deacetylation. Together, these altered pathways induce mitochondrial dysfunction that is implicated in aging and disease. Other potentially important processes impacted by decreased sirtuin levels – for example, epigenetic changes through histone modifications and DNA repair pathways, among others – are likely to contribute to cellular phenotypes, and are not depicted here.
See this image and copyright information in PMC

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