Uncovering a “Smoking Gun” in Age-Related Disease
Aging is a key risk factor for a variety of devastating chronic diseases, yet the biological factors that influence when and how rapidly cells deteriorate over time remain largely unknown. Now, for the first time, a research team led by Harvard T.H. Chan School of Public Health has linked the function of a core component of cells’ machinery — which cuts and rejoins RNA molecules in a process known as “RNA splicing” — with longevity in the roundworm. The finding sheds light on the biological role of splicing in lifespan and suggests that manipulating specific splicing factors in humans might help promote healthy aging.
The study was published in the December 5th, 2016 advance online issue of Nature.
A release from Harvard quotes William Mair, assistant professor of genetics and complex diseases at Harvard Chan School and the study’s senior author, as saying, “What kills neurons in Alzheimer’s is certainly different from what causes cardiovascular disease, but the shared underlying risk factor for these illnesses is really age itself. So one of the big questions is: Is there a unifying theme that unfolds molecularly within various organ systems and allows these diseases to take hold?”
Due to advances in public health, life expectancy has dramatically increased worldwide over the last century. Although people are generally living longer lives, they are not necessarily living healthier lives, particularly in their last decades. Age-related diseases such as cancer, heart disease, and neurodegenerative disease are now among the leading global health burdens — a problem that will likely only worsen.
In order for bodies — and cells — to maintain youthfulness, they must also maintain proper homeostasis. At the cellular level, that means keeping the flow of biological information, from genes to RNA to proteins, running smoothly and with the right balance.
While a considerable amount is known about how dysfunction at the two ends of this process — genes and proteins — can accelerate aging, strikingly little is known about how the middle part, which includes RNA splicing, influences aging. Splicing enables one gene to generate multiple proteins that can act in different ways and in disparate parts of the body.
“Although we know that specific splicing defects can lead to disease, we were really intrigued about de-regulation of RNA splicing as a driver of the aging process itself, because practically nothing is known about that,” said Mair. “Put simply, splicing is a way for organisms to generate complexity from a relatively limited number of genes.”