Exercise and Live
Exercise Enzyme Extends Lifespan
Activated in muscles, it may explain some beneficial effects of physical activity
 Credit: Diane Diederich Body pump: An enzyme activated in muscles by exercise extends life in the lab and could provide targets for life-extending drugs |
The enzyme, AMP-1, is a molecular sensor activated by a small molecule called AMP. AMP is generated as the final product of ATP, which cells use to store and transfer energy.
"It is tempting to speculate that perhaps some of the beneficial effects of exercise in human health are the result of the effect of AMP-1 activation on the aging process," says Javier Apfeld of Cambridge, Massachusetts-based Elixir Pharmaceuticals.
Energy conservation
When activated, AMP initiates reactions that cause the body to conserve energy stores. Limiting the availability of energy has shown in trials of caloric restriction to extend healthy lifespan.
Apfeld and colleagues now report that they've shown in lab worms that an enzyme called AAK-2 that's the equivalent of AMP-1 in humans plays a role in life extension.
"The discovery that a sensor of energy levels regulates lifespan is very exciting because it tells us that the worm is actively making a decision in adjusting its lifespan in response to its energy state," says Apfeld.
Activating longevity
The researchers found that by giving extra copies of the enzyme to nematode worms, the worms lived an average of 13% longer than controls. They also report that environmental stressors that activate the enzyme extend lifespan.
Additionally, they found that nematodes with a mutant enzyme were unable to cope with the same environmental stressors, showing that it plays a protective role.
Looking at the influence of the enzyme on other molecular pathways that regulate lifespan, the researchers found that it may work alongside such previously established pathways as Daf-16, which encodes a transcription factor thought to promote stress resistance and longevity.
The findings have implications for understanding human aging and developing life-extending treatments. AAK-2 and AMP-1 work similarly in humans and nematodes. By learning more about how the enzymes trigger energy conservation, researchers could develop drugs that have a similar effect.
"This work supports our premise that aging is highly regulated and extends our list of molecular targets in pathways that affect lifespan by controlling metabolic processes," says Peter DiStefano, Elixir's chief scientific officer.
The research is reported in the journal Genes & Development (read abstract).
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