What causes cells in our bodies to stop reproducing and eventually die? This proverbial question certainly plagues the sleep of many a trophy wife and a world of scientists in every field from medicine to genetics.
New research from the Viterbi School of Engineering at the University of Southern California has revealed a key element to cellular rejuvenation that could prove foundational in forward-thinking cancer therapies, drugs related to twilight-years aging symptoms, as well as leading to new frontiers in fountain-of-youth approaches to beauty. Nucleotides appear to be the necessary master key to pick the lock of the cellular clock.
What is senescence?
Like all organic matter on Earth, cells have an expiration date. The natural mechanism through which a cell will one day completely cease to make new cells ever again is called senescence.
All age-related decline stems from this process. Common ailments that we all think of as simply unavoidable parts of getting older, such as osteoporosis or heart disease, all originate in senescence. The lead author of this study, Alireza Delfarah, characterizes senescent cells as "the opposite of stem cells" and describes "an irreversible state of cell cycle arrest" with relation to this phenomenon.
How is senescence connected to cellular aging?
The Viterbi team was able to show that cells which had passed into a senescent state no longer produced nucleotides, the class of chemicals essentially understood to be the crucial foundation of DNA. When forcibly deprived of the ability to produce nucleotides, even young cells lapsed into the senescent state.
This revelation leads to a deeper understanding of how nucleotide synthesis could be manipulated in a way that would allow cells to age at a much slower pace. Via a combination of 3D imaging and the active feeding of stable carbon isotopes to molecules, this group of USC scientists was able to track nutrient consumption and discover that two nuclei, neither of which synthesized DNA, were nearly always present in senescent cells.
What's new in this study and what's the impact?
Prior studies on cellular aging have focused on fibroblasts as these cells make up the vast majority of connective tissue in most animals. This breakthrough study has instead made epithelial cells the central focus of its domain and in doing so has emphasized the kind of cells responsible for the exterior and interior linings of organs. These also happen to be the most common kind of cells in which cancer may arise.
Herein lies the rub: senescense appears to be the human body's built-in cancer mote. When faced with cells that seem at risk for becoming cancerous, the cells of our bodies swing into the senescent state in order to prevent the disease from spreading.
So, the unshocking truth is that you cannot have your noncarcinogenic youth cake and eat it too. We cannot seek to completely halt senescence within human cells without leaving ourselves vulnerable to "the big C."
Finding the best balance
The field of senolytics, the study and development of drugs that may help to slow down or buffer aging cells, is gaining steam. The collective goals is to age better, and with more productivity involved in the process, not to extend life forever.
Clinical trials involving mice have affirmed that senolytic drugs aimed at distinguishing between the metabolic pathways of senescent versus non-senescent cells, restore and elevate aging mice back to a more energetic, youthful state. While there are still long roads to explore in discovering how we might design eternal youth drugs that somewhat curate and allow us to manipulate senescent cells, there is an equal amount of road we must travel in learning exactly how these cells are exclusive and extraordinary.