James F. Dice Jr.
Aging cell by cell
It's true for cells in culture, rats, fruit flies, nematodes, yeast and in every tissue of humans: The older the cell, the longer it takes to dispose of used proteins.
"We have proteins hanging around in the cytoplasm of aging cells five times longer than they should," says James F. Dice Jr. "They have five times the chance to be damaged and to cause damage." Eventually, they contribute to the aging of the cell and the aging of the organism—if aging is defined as biological deterioration.
Dice, professor of physiology at the School of Medicine, has one of a handful of research laboratories in the world that intensely investigates lysosomes, often called the cell's stomach because they are responsible for "digesting" or degrading about half the proteins produced in the cell and extracting and recycling amino acids.
Dice's lab concentrates on one of two known lysosomal protein degradation pathways, the mechanisms that deliver the proteins to the lysosomes. Dice wants to find ways to repair that pathway in hopes of restoring the cell's health, perhaps even extending its reproductive life. "We know that if cells have enough damaged DNA, they won't go through a cell division cycle," Dice says. "I think there's something similar that happens with an accumulation of damaged protein."
Dice's lab has found that the molecules that usher proteins through the lysosome membrane decline in number as the cell ages. The lab currently is investigating whether increasing the number of these molecules will reverse sluggish degradation rates. Results so far are promising.
There's no "silver bullet" to kill aging, Dice says, although he does think there is hope for developing an amalgam bullet. "It's clear now that several things will have to be corrected at the same time—for instance, both the repair of DNA and protein degradation pathways—to take care of some of the molecular and cellular roots of aging."