Genetic switch may be key to increased lifespan

Scientists have discovered genetic switches in worms that are also linked to increased lifespan in mammals and may be targeted by drugs to improve human metabolic function and increase longevity.

These epigenetic switches, discovered by scientists at the University of California, Berkeley, and the Ecole Polytechnique Federale de Lausanne in Switzerland, are enzymes that are ramped up after mild stress during early development and continue to affect the expression of genes throughout the animal's life.

When researchers looked at strains of inbred mice that have radically different lifespans, they found that those with the longest lifespans had significantly higher expression of these enzymes than the short-lived mice.

"Two of the enzymes we discovered are highly correlated with lifespan; it is the biggest genetic correlation that has ever been found for lifespan in mice, and they are both naturally occurring variants," said Andrew Dillin from the University of California, Berkeley.

"Based on what we see in worms, boosting these enzymes could reprogramme your metabolism to create better health, with a possible side effect of altering lifespan," said Dillin.

These are the first epigenetic modifiers known to



affect metabolic function and longevity, though others are known to affect either metabolism or lifespan, researchers said.

For decades, researchers have found correlations between nutrient availability during early development and adult health and metabolism.

Brief changes in the energy available to the cell - caused by restricting diet, for example - seem to reshape animal physiology for years to come, even affecting lifespan. These observations led to the idea that reducing cellular energy production could slow the ageing process and make organisms live longer.

These energy restrictions had to occur during a specific window of development in order to affect the ageing process, suggesting the existence of a critical metabolic switch that could remodel cellular functions throughout the organism's entire lifespan, researchers said.

They focused their search on the power factory of the cell, the mitochondria.

Malfunctioning mitochondria have been reported as a cause or a consequence of nearly every single age-onset human disease, including Alzheimer's and Parkinson's disease, heart disease, type 2 diabetes and cancer, said Dillin.

The findings were published in the journal Cell.