Cell Senescence - Introduction by Dr.M.Jothimuniyandi

Cell Senescence - Introduction - concept - character - molecular pathways -roles

1. Cell senescence Dr.M.Jothimuniyandi

2. Concept Cell senescence is a biological process in which a cell permanently loses its ability to divide and function optimally. This phenomenon can be triggered by various internal and external factors and has significant implications for aging and disease. .

3. Triggers of Senescence Telomere Shortening : Telomeres are protective caps at the ends of chromosomes. Each time a cell divides, telomeres shorten. When they become critically short, the cell can enter senescence. DNA Damage : Accumulation of DNA damage from environmental factors (like UV radiation) or internal processes (like oxidative stress) can induce senescence. Oxidative Stress : High levels of reactive oxygen species (ROS) can damage cellular components and trigger senescence. Oncogene Activation : Activation of certain cancer-related genes can induce a senescence response as a protective mechanism against uncontrolled cell growth.

4. Characteristics of Senescent Cells Cell Cycle Arrest : Senescent cells stop dividing and exit the cell cycle permanently. Morphological Changes : These cells often exhibit changes in shape, such as increased size and altered cell structure. Altered Gene Expression : Senescent cells show changes in the expression of various genes, including those involved in inflammation and stress responses. Senescence-Associated Secretory Phenotype (SASP) : Senescent cells secrete a variety of factors, including cytokines, growth factors, and proteases, which can affect surrounding cells and tissues.

5. Molecular Pathways p53 Pathway : Activated by DNA damage or telomere shortening, p53 regulates cell cycle arrest by inducing p21CIP1. It also triggers apoptosis in some contexts but can lead to senescence if damage is chronic. p16INK4a Pathway : This tumor suppressor protein inhibits cyclin D-CDK4/6 complexes, crucial for the G1 to S phase transition. Increased p16INK4a levels are associated with senescence, especially in response to oncogene activation or telomere shortening.

6. Roles in Health and Disease Aging : Accumulation of senescent cells contributes to the aging process and age-related diseases by promoting inflammation and tissue dysfunction. Cancer : Senescence acts as a barrier to cancer development by preventing the proliferation of damaged cells. However, the SASP can sometimes support tumor growth and progression. Tissue Repair : Senescence can play a role in wound healing and tissue repair, but an excess of senescent cells can impair these processes.

7. Therapeutic Strategies Senolytics : Drugs that selectively eliminate senescent cells are being researched to mitigate age-related diseases and improve health. Senomorphics : Compounds that modify the SASP to reduce its harmful effects without killing senescent cells. Genetic and Cellular Interventions : Techniques like gene editing and stem cell therapies are explored to manage or reverse the effects of senescence.

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