Enzyme inhibitor extends lifespan in mice started in late life
Very few interventions can still extend lifespan in mice when treatment begins late. An enzyme inhibitor now appears to belong to that small group, adding months to median survival in both male and female mice.
When researchers want to test whether a compound truly acts against aging, they prefer to start treatment late. That way they know the substance works in already-aged animals, not just young ones. Only a handful of compounds have shown results in that setting. Inhibition of an enzyme called asparagine endopeptidase (AEP, also known as legumain) now appears to join that limited group.
Four months of extra median survival in mice
The researchers began treatment in mice at 18 months of age, roughly equivalent to humans in their fifties. They found a four-month gain in median survival, from 24 to 28 months. That is comparable to the effect of rapamycin, another compound that extends lifespan in mice when started in late life. The treated mice also showed improvement across multiple measures of frailty.
AEP is an enzyme that breaks down proteins inside lysosomes, the cell's recycling compartments. With aging, the enzyme becomes overactive. It then cleaves proteins at unintended sites, disrupting normal cell function. This may lead to an accumulation of damaged material and declining energy production in cells. The researchers suggest that inhibiting AEP can slow that cascade.
Similar to rapamycin, through a different route
AEP inhibition appears to work, like rapamycin, through improved energy production in cells and reduced accumulation of aging, worn-out cells. But the mechanism differs: the researchers suggest AEP inhibition directly improves how cells produce energy, possibly without engaging the cellular recycling process that rapamycin activates. This is mouse research; whether the same route operates comparably in people has not been investigated.
Search terms to explore further: asparagine endopeptidase legumain aging, lysosomal protein degradation cellular senescence, energy metabolism lifespan mice