A recent toast to James Watson highlights a tolerance for bigotry many want excised from the scientific community.
Editor's choice in developmental biology
June 14, 2011|
ALEXEI PROTOPOPOV, PH.D. BELFER INSTITUTE FOR APPLIED CANCER SCIENCES
E. Sahin et al., “Telomere dysfunction induces metabolic and mitochondrial compromise,” Nature, 470:359-65, 2011. Free F1000 evaluation
Many cellular processes have been implicated in aging, but how these systems interact has remained a mystery. Ron DePinho of Dana-Farber Cancer Institute linked DNA damage from telomere dysfunction to reduced mitochondrial function, placing “telomeres and mitochondria right in the same axis of aging science,” DePinho says.
In a mouse model of aging, animals with short telomeres display downregulated mitochondrial master regulator proteins known as PGCs as well as increased heart failure and liver dysfunction. When researchers forced expression of telomerase to rebuild telomeres, or when the PGC proteins were overexpressed, the aging phenotype was partially rescued.
In these mice, p53 overexpression led to mitochondrial dysfunction via blocking PGC expression. Conversely, when researchers knocked out p53, which responds to telomere shortening by triggering DNA repair, mitochondrial functions were partially restored. Thus p53 directly links telomeric aging to mitochondrial function, tying “loose ends into a common thread,” writes Kevin Conley in his F1000 evaluation.
Free radicals are normal byproducts of the mitochondrial electron transport chain, though they can cause DNA damage. DePinho’s work suggests that telomere degradation exacerbates a feedback loop in which short-telomere-instigated suppression of mitochondrial regulation leads to the generation of more free radicals, suggesting the value of moderating this pathway in age-related diseases, says DePinho.