As time marches on, aging is inevitable. Naturally, a person can accumulate wrinkles, laugh lines, stress, and cellular damage. Of these, damaged cells can take multiple paths: they can undergo programmed death; they can proliferate uncontrollably and become cancer; or they can become senescent cells.
Miranda Orr studies cellular senescence as one of the hallmarks of importance in Alzheimer’s disease.
Courtesy of Miranda Orr
They don’t claw their way out of graves, but senescent cells are the body’s biological zombies—damaged, unable to divide, but very much metabolically alive. Instead of dying like normal cells, these “undead” entities can avoid immune system clearance and linger in the brain and other parts of the body.
“They are no longer the original cell that they once were,” explained Miranda Orr, a translational neuroscientist at Washington University School of Medicine (WashU Medicine). Orr added that senescent cells not only differ from their initial form but also vary by the cell type within the tissue they came from, the stress triggers, and whether the aging process is healthy or pathological.
Cellular senescence has a complex relationship with the body.1 These cells have beneficial roles in development, tissue regeneration, and wound healing. In some cases, they are physiologically senescent cells, meaning they are neither harmful nor linked to aging.
Senescence also plays a double-edged role in cancer. It can act as a protective mechanism by halting the proliferation of damaged or potentially cancerous cells. Alternatively, senescent cells can promote tumor development through the release of pro-inflammatory and tissue-altering molecules, known as the senescence-associated secretory phenotype (SASP).2 These cells can also damage and “infect” neighboring cells.
In healthy aging brain tissue, vascular smooth muscle cells can become senescent; however, in diseases like Alzheimer’s disease, neurons, astrocytes, oligodendrocyte precursor cells, and microglia are more affected.3 Orr said, “The [neuroscience] field is now spending so much effort in identifying and profiling senescent cells.”
To better understand these variations, scientists, including Orr, are cataloging senescent cells in the Cellular Senescence Network database and developing therapies such as senolytics (which eliminate senescent cells) and senomorphics (which suppress their harmful secretions).4 While Orr acknowledged there is more work to be done, she is optimistic about the momentum and ongoing advancements in senescent cell research.
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