ROS Production by Dysfunctional Mitochondria Leads to Cell Senescence and Bone Aging

Roma Bhandarkar

 Introduction. Some damaged cells display cellular senescence, which is a stress response that results in permanent cell cycle arrest 2. Senescent cells secrete chemicals known as senescence-associated secretory phenotype (SASP) that drive pathologies associated with aging, such as osteoarthritis 3. Osteoarthritis is a chronic disease characterized by degeneration of articular cartilage leading to pain and physical disability 3. Osteoarthritis can affect any joint, but it most commonly affects joints of the hands, knees, hips, and spine 3Aging and trauma are risk factors for the development of osteoarthritis 3. Mitochondrial dysfunction produces reactive oxygen species (ROS) that cause Ras expressing cells to induce cell cycle arrest 4. Methods. INK-ATTAC suicide transgene encodes for caspase 8 which contributes to bone aging. Mice studies have shown that decreasing mRNA expression of caspase 8 results in mice with higher bone mass and strength 1. Adenine nucleotide translocase-2 (ANT2) is a mitochondrial carrier protein that is involved in translocating ATP that is produced via glycolysis by the mitochondria. Mice studies have shown that downregulating ANT2 contributes to cell senescence 2. Treatments. Senolytics can be used to reduce senescent-cell burden, which suppresses bone resorption by either increasing or maintaining bone formation 1. Anticancer agents such as tamoxifen (MitoTam) that targets mitochondria, eliminates both malignant and non-cancerous senescent cells, which may be a new strategy for the treatment of senescence-associated pathologies 2. Discussion. Mitochondrial dysfunction produces reactive oxygen species that induce cell cycle arrest, this leads to senescent cells that secrete chemicals that drive pathologies associated with aging. Adenine nucleotide translocase-2 and INK-ATTAC suicide transgene are molecular elements that play a role in cellular senescence and bone aging. Senolytics and anticancer agents may be possible treatments for ROS induced senescent bone aging.

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