Energy Metabolite Extends A Worm’s Life

A study has shown that using the energy production pathway metabolite α-keto­glutarate (α-KG) as a nutritional supplement can extend roundworm life span by 50%. The finding could lead to the development of new strategies for the prevention and treatment of aging and age-related diseases, the study’s authors say (Nature 2014, DOI: 10.1038/nature13264). Scientists have long known that dietary restriction increases longevity in many species, such as roundworms, mice, and monkeys. Numerous intertwined metabolic pathways may be involved in the diet-influenced modulation of aging, with roles played by small-molecule metabolites such as oxaloacetate, malate, and α-KG. A team led by UCLA’s Jing Huang has discovered that α-KG extends life span and determined its mechanism. The metabolite binds to the enzyme ATP synthase, inhibiting the assembly of adenosine triphosphate, a key energy-supplying biomolecule in most organisms. α-KG also inhibits TOR, a protein involved in aging. The rise of α-KG levels during starvation further links the molecule to diet and aging. Metabolism and aging specialist Matthew S. Gill of Scripps Research Institute Florida says the research “is an important addition to the list of molecular targets and mechanisms that have the potential to influence human health span.”