Unlike embryonic stem cells, adult human cells have a finite number of lives. Once they divide a certain number of times, they change shape, slow their pace, and eventually stop dividing, a phenomenon called "cellular senescence."
Biologists know that a cellular clock composed of structures at the chromosome end known as telomeres records how many "lives" a cell has expended. Up to now, researchers have not defined how the clock's ticking signals the approach of cellular oblivion.
Now, researchers report that as cells count down to senescence and telomeres wear down, their DNA undergoes massive changes in the way it is packaged. These changes likely trigger what we call "aging."
"Prior to this study we knew that telomeres get shorter and shorter as a cell divides and that when they reach a critical length, cells stop dividing or die," said Jan Karlseder, Ph.D., associate professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies. "Something must translate the local signal at chromosome ends into a huge signal felt throughout the nucleus. But there was a big gap in between."
Karlseder and postdoctoral fellow Roddy O'Sullivan, Ph.D., began to close the gap by comparing levels of proteins called histones in young cells—cells that had divided 30 times—with "late middle-aged" cells, which had divided 75 times and were on the downward slide to senescence, which occurs at 85 divisions. Histone proteins bind linear DNA strands and compress them into nuclear complexes, collectively referred to as chromatin.
Karlseder and O'Sullivan found that aging cells simply made less histone protein than do young cells. "We were surprised to find that histone levels decreased as cells aged," said O'Sullivan. "These proteins are required throughout the genome, and therefore any event that disrupts this production line affects the stability of the entire genome."
