The continual and inevitable shortening of telomeres, the protective caps at the end of all 46 human chromosomes, has been linked to aging and physical decline. Once they are gone, so are we. But there are more ways than one to grow old.
Researchers at Salk Institute for Biological Studies demonstrate for the first time that the roundworm Caenorhabditis elegans succumbs to the trials of old age although its telomeres are still long, and moves with a youthful spring in its crawl despite short telomeres, they report in PLoS Genetics.
In the past, preventing telomere shortening has often been portrayed as the key to preventing aging and living longer. In their study, Salk scientists Jan Karlseder, an assistant professor in the Regulatory Biology Laboratory, and Andrew Dillin, an assistant professor in the Molecular and Cell Biology Laboratory, provide a much more nuanced view of telomeres and the process of cellular and organismal aging.
Each time a cell divides, its telomeres get shorter, a process called replicative or cellular aging. Some have likened this progressive erosion of telomeres to a genetic biological clock that winds down over time, leading to a gradual decline in our mental and physical prowess. Yet, C. elegans, a tiny creature, which spends the better part of its adult life without a single dividing cell in its body, still shows signs of old age and eventually dies, raising intriguing questions.
Are telomeres in non-dividing cells eroding slowly over time? If so, will worms with longer telomeres live longer? To answer these vexing questions, Karlseder teamed up with Dillin, who studies lifespan and aging in C. elegans.
Many cells in our body keep dividing throughout life - like those that line our digestive tract, blood and immune cells - because they must be replaced over time. When these cells’ telomeres reach a critically short length, however, they can no longer replicate. The cell’s structure and function begin to fail as it enters this state of growth arrest, called replicative senescence.
“But even in very old people, blood cells, which divide continuously, don’t have critically short telomeres. In humans and, as we know now, in worms, telomere length is certainly not a limiting factor for lifespan,” said Karlseder.
“For successful aging you have to control both, aging in your dividing cells, which hinges on telomere maintenance, but also aging in your non-dividing cells. We thought that telomeres might play a role in the latter but that’s clearly not the case,” said Dillin. “What is probably playing a role in the other half of aging is the insulin signaling pathway, proper mitochondrial function and dietary restriction,” he reasons.