Altering Cellular Energy With Key Protein Increases Lifespan In Worms

Credit: Goehring et al. (2011) J. Cell Biol. 193, 583-594.

Increasing levels of a protein involved in cellular energy called arginine kinase-1 increases longevity in the model organism C. elegans

Energy sensing and management is one of the first pathways that proved able to extend organism lifespan in the lab, and it remains an intriguing area for therapeutic targeting today.

Worms with a particular genetic change that robs them of enzyme called s6 kinase live 25% longer than your ordinary C. elegans worn. Reducing levels of this enzyme in mice has also been proven to have beneficial effects – leading to the hypothesis that the pathway is evolutionarily conserved. This means that it’s probably present in humans, and could well have a similar influence on aging processes (although likely less impressive).

“We found that longevity can be extended by increasing the amount of a protein called arginine kinase-1 (ARGK-1). ARGK-1 maintains ATP availability within cells, and we suspect that increased levels trigger a fuel sensor, regulating energy homeostasis and extending lifespan”

In humans creatine kinase converts creatine to phosphocreatine

After examining protein levels in these long-lived s6 worms, a team based at the Sanford Burnham Prebys Medical Discovery Institute uncovered that levels of ARGK-1 were 30 times higher in comparison to the control group. Following this revelation, they deliberately raised levels of ARGK-1 in normal worms which had a similarly longevity promoting effect.

The human equivalent of ARGK-1 is called creatine kinase and its substrate creatine has curiously been shown to have health-promoting effects in disease like Parkinson’s. At the moment these results are extremely tentative and work on worms regularly fails in humans, but data like this can still teach us about which processes affect and are affected in turn by aging.

“Our main goal in studying aging is not to find ways to extend human lifespan, but to understand the processes by which our cells and tissues become less functional over time. In cancer, some tumors highly activate S6K to feed tumor growth. Further work to understand the relationship between creatine kinase and S6K may lead to new avenues to pursue novel drugs for age-related diseases, including cancer”

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