A roadmap for metabolic reprogramming of aging

To survey previously uncharted territory, a team of researchers at UW-Madison has created an “atlas” that maps more than 1,500 unique landmarks within mitochondria that could provide clues to the metabolic connections between caloric restriction and aging.
 
The map, as well as the techniques used to create it, could lead to a better understanding of how cell metabolism is rewired in some cancers, age-related diseases and metabolic conditions such as diabetes.
 
“It’s really a dynamic atlas for regulatory points in mitochondrial function — there are many interesting avenues that other scientists can follow up on,” says John Denu, University of Wisconsin-Madison professor of biomolecular chemistry and leader of the epigenetics theme at the Wisconsin Institute for Discovery (WID). “It could take years for researchers to understand what it all means, but at least now we have a list of the most important players.”
 
In previous experiments, it’s been shown that consuming less food increases the life span and health span in a range of organisms, from yeast and flies to mice and nonhuman primates. But pinpointing where and how caloric restriction affects cells at a molecular level remains the challenge.
 
So far, mitochondrial proteins, the molecules that command specific actions in the cell’s powerhouse organelle, are at center stage of metabolic reprogramming.
 
Denu and colleagues conducted earlier research on the mitochondrial protein Sirt3, where they suggested a link between Sirt3 and the benefits of caloric restriction in situations such as the prevention of age-related hearing loss.