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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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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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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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Techniques to Induce and Quantify Cellular Senescence
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The persistent dynamic secrets of senescence.

Clemens A Schmitt1

  • 1Charité-Universitätsmedizin Berlin, Medical Department, Division of Hematology, Oncology and Tumor Immunology, and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Augustenburger Platz 1, 13353 Berlin, Germany.

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Summary

The NOTCH pathway dynamically regulates cellular senescence, orchestrating a two-phase secretome. This involves an initial pro-senescent phase followed by a pro-inflammatory, senescence-clearing phase.

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Area of Science:

  • Cellular biology
  • Molecular mechanisms of aging
  • Signaling pathways

Background:

  • The role of the senescence-associated secretome in health and disease is debated.
  • Time-resolved analyses of senescence secretome composition and function are lacking.

Discussion:

  • NOTCH signaling dynamically controls two distinct senescence phenotypes.
  • The first phase involves a transforming growth factor-beta 1 (TGF-β1)-dependent pro-senescent secretome.
  • The second phase is characterized by pro-inflammatory cytokines that clear senescent cells.

Key Insights:

  • NOTCH signaling acts as a key regulator of senescence.
  • The study reveals a temporal duality in senescence-associated secretome.
  • This provides a mechanistic link between NOTCH, senescence, and inflammation.

Outlook:

  • Further research into NOTCH-mediated senescence could reveal therapeutic targets.
  • Understanding these distinct phases may clarify the beneficial versus detrimental roles of senescence.
  • This work opens new avenues for investigating senescence clearance mechanisms.