Removing zombie (senescent) cells using senolytics slows the aging process
Aging is characterized by a gradual functional decline. In mammals, aging occurs across multiple organ systems, causing a progressive deterioration that eventually results in tissue dysfunction. Consequently, age is a risk factor for many diseases, such as cardiovascular disease, dementia, osteoporosis, osteoarthritis, cancer, type 2 diabetes, idiopathic pulmonary fibrosis, and glaucoma. Despite these links with human pathology, the understanding of the aging process remains limited but it has been discussed that zombie cells in our body have an impact in the aging process.(1) To be more specific zombie cells are a common, non-dividing cell type called Senescent cells (5). The cells in our bodies also have the ability to become senescent at some time or another. DNA damage due to radiation exposure, chemotherapy, telomere shortening and metabolic stress including high fat have been shown to promote a normal cells to enter a senescence phase. Senescence is cellular program that induces a stable growth arrest to ensure that further damage to other cells are not caused. When a cell enters the senescence phase it stops producing copies of itself, begins to release hundreds of proteins, and activates anti-death pathways. This pathway is activated due to persistent DNA damage response due to chronic genomic stress or telomere attrition leads to activation of several signaling pathways that lead to cellular senescence including the p53 and p16 pathway. The p53 activates p21 which deactivates cyclin-dependent kinase 2 (Cdk 2). Without Cdk 2, retinoblastoma protein (pRB) remains in its active, unphosphorylated form which prevents E2F mediated transcription thus preventing genes essential for DNA replication and proliferation.
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Recent studies have shown a new solution that could delay the aging process, just by removing zombie (senescent cells), all cells in our bodies are at a risk of becoming senescent due to exposure of harmful stimuli that activate a specific signaling pathway. Senescent cells have undergone permanent growth arrest, adopt an altered secretory phenotype, and accumulate in organs with ageing and injury. Recent studies have shown that depletion of senescent cells extends healthy lifespan and delays ageassociated disease—proving that senescence and the senescence-associated secretory phenotype are causative agents of organ dysfunction. Great interest is therefore focused on the manipulation of senescence as a novel therapeutic target in many age related disease by using a cocktail of drugs known as senolytics, these reduce the zombie cell count to delay aging by the intermittent administration of the senolytic drug combination, Dasatinib and Quercetin, which transiently disables the prosurvival pathways that defend senescent cells against their own apoptotic environment, selectively eliminates senescent cells in mice and human cell cultures. In the first clinical trial of senolytics, they decreased physical dysfunction in patients with idiopathic pulmonary fibrosis (IPF), a progressive, fatal, cellular senescenceassociated disease. In another clinical trials, usage of the senolytic mixture improved the health of patients with diabetic kidney disease, osteoarthritis and age related immunosuppression.
