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Replicative Cell Senescence02:15

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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
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Aging01:26

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Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
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Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
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Induction and Validation of Cellular Senescence in Primary Human Cells
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COVID-19 and cellular senescence.

Clemens A Schmitt1,2,3,4,5, Tamar Tchkonia6, Laura J Niedernhofer7

  • 1Charité-Universitätsmedizin Berlin, Medical Department of Hematology, Oncology and Tumour Immunology, and Molekulares Krebsforschungszentrum-MKFZ, Campus Virchow Klinikum, Berlin, Germany. clemens.schmitt@charite.de.

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Cellular senescence, a key aging process, exacerbates COVID-19 severity by promoting inflammation and tissue damage. Eliminating senescent cells may offer a new therapeutic strategy for COVID-19 and other infections.

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Area of Science:

  • Aging and Immunology
  • Viral Pathogenesis

Background:

  • Host factors significantly influence COVID-19 clinical severity.
  • Cellular senescence, an aging-related cellular state, is increasingly recognized as a critical regulator of SARS-CoV-2-induced hyperinflammation.

Purpose of the Study:

  • To investigate the role of cellular senescence and its associated secretory phenotype (SASP) in the pathogenesis of COVID-19.
  • To explore the potential of senolytic therapies in mitigating COVID-19 severity.

Main Methods:

  • Review of recent advances in understanding cellular senescence and SASP.
  • Analysis of preclinical and early clinical data on senolytic interventions in viral infections.

Main Results:

  • SARS-CoV-2 infection can induce cellular senescence and exacerbate the SASP, characterized by pro-inflammatory and pro-coagulatory factors.
  • Elderly individuals with higher pre-existing senescent cell burdens experience enhanced SASP effects, contributing to cytokine storms, tissue damage, and microthrombosis.
  • SASP-driven senescence spreading amplifies inflammation and tissue injury, uncoupled from direct viral damage.

Conclusions:

  • Targeted elimination of senescent cells (senolytics) presents a promising therapeutic avenue to reduce COVID-19 clinical deterioration.
  • Senolytic therapies may enhance host resilience against SARS-CoV-2 and other pathogens.