Summary: Researchers have uncovered an anti-aging function in a protein, ATSF-1, found deep within human cells. This protein controls a delicate balance between the creation and repair of mitochondria, which produce energy and contribute to cell aging.
By enhancing ATSF-1 function, cellular health was improved in a study using C. elegans worms. This discovery could have major implications for healthy aging and mitochondrial diseases.
The protein ATSF-1, found within human cells, can regulate the creation and repair of mitochondria, impacting cell aging.
By enhancing ATSF-1 function, researchers improved cellular health in roundworms, suggesting possible benefits for human health.
This study may pave the way for interventions that prolong organ functions typically affected by aging, potentially improving quality of life.
Source: University of Queensland
Researchers at The University of Queensland have found an anti-aging function in a protein deep within human cells.
Associate Professor Steven Zuryn and Dr Michael Dai at the Queensland Brain Institute have discovered that a protein called ATSF-1 controls a fine balance between the creation of new mitochondria and the repair of damaged mitochondria.
Mitochondria, with their own DNA, produce energy within cells to power biological functions but the toxic by-products of this process contribute to the rate at which the cell ages.
“In conditions of stress, when mitochondrial DNA has been damaged, the ATSF-1 protein prioritises repair which promotes cellular health and longevity,” Dr Zuryn said.
As an analogy, Dr Zuryn likened the relationship to a race car needing a pitstop.
“ATSF-1 makes the call that a pitstop is needed for the cell when mitochondria need repairs,” he said.
“We studied ATFS-1 in C. elegans, or round worms and saw that enhancing its function promoted cellular health, meaning the worms became more agile for longer.
“They didn’t live longer, but they were healthier as they aged.”
“Mitochondrial dysfunction lies at the core of many human diseases, including common age-related diseases such as dementias and Parkinson’s.
“Our finding could have exciting implications for healthy aging and for people with inherited mitochondrial diseases.”
Understanding how cells promote repair is an important step towards identifying possible interventions to prevent mitochondrial damage.
“Our goal is to prolong the tissue and organ functions that typically decline during aging by understanding how deteriorating mitochondria contribute to this process,” Dr Dai said.
“We may ultimately design interventions that keep mitochondrial DNA healthier for longer, improving our quality of life,” Dr Dai said.
ATFS-1 counteracts mitochondrial DNA damage by promoting repair over transcription
The ability to balance conflicting functional demands is critical for ensuring organismal survival. The transcription and repair of the mitochondrial genome (mtDNA) requires separate enzymatic activities that can sterically compete1, suggesting a life-long trade-off between these two processes.
Here in Caenorhabditis elegans, we find that the bZIP transcription factor ATFS-1/Atf5 regulates this balance in favour of mtDNA repair by localizing to mitochondria and interfering with the assembly of the mitochondrial pre-initiation transcription complex between HMG-5/TFAM and RPOM-1/mtRNAP.
ATFS-1-mediated transcriptional inhibition decreases age-dependent mtDNA molecular damage through the DNA glycosylase NTH-1/NTH1, as well as the helicase TWNK-1/TWNK, resulting in an enhancement in the functional longevity of cells and protection against decline in animal behaviour caused by targeted and severe mtDNA damage.
Together, our findings reveal that ATFS-1 acts as a molecular focal point for the control of balance between genome expression and maintenance in the mitochondria.