Intact mitochondrial function in the setting of telomere-induced senescence

Mitochondria play essential roles in metabolic support and signaling within all cells. Congenital and acquired defects in mitochondria are responsible for several pathologies, including premature entrance to cellar senescence. Conversely, we examined the consequences of dysfunctional telomere-driven cellular senescence on mitochondrial biogenesis and function. We drove senescence in vitro and in vivo by deleting the telomere-binding protein TRF2 in fibroblasts and hepatocytes, respectively. Deletion of TRF2 led to a robust DNA damage response, global changes in transcription, and induction of cellular senescence. In vitro, senescent cells had significant increases in mitochondrial respiratory capacity driven by increased cellular and mitochondrial volume. Hepatocytes with dysfunctional telomeres maintained their mitochondrial respiratory capacity in vivo, whether measured in intact cells or purified mitochondria. Induction of senescence led to the upregulation of overlapping and distinct genes in fibroblasts and hepatocytes, but transcripts related to mitochondria were preserved. Our results support that mitochondrial function and activity are preserved in telomere dysfunction-induced senescence, which may facilitate continued cellular functions.

Automated summary

Mitochondria play important roles in cellular metabolism and signaling. Defects in mitochondria caused by genetic or acquired factors can lead to various pathologies, including premature cellular senescence. In this study, we investigated the effects of dysfunctional telomeres on mitochondrial biogenesis and function during senescence. Our results showed that senescent cells had increased mitochondrial respiratory capacity and volume. Even in vivo, hepatocytes with dysfunctional telomeres maintained their mitochondrial respiratory capacity. The upregulation of genes related to mitochondria was observed during senescence in fibroblasts and hepatocytes. These findings suggest that mitochondrial function and activity are preserved in telomere dysfunction-induced senescence.