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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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In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
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Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
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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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From Genome to Geroscience: How DNA Damage Shapes Systemic Decline.

Athanasios Siametis1,2, George A Garinis1,2

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Summary
This summary is machine-generated.

Genomic instability from DNA damage triggers harmful inflammation and tissue decline, accelerating aging. Targeting these DNA damage responses may offer new strategies to delay age-related diseases.

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Area of Science:

  • Cellular and Molecular Biology
  • Aging Research
  • Immunology

Background:

  • Persistent genomic instability impairs cell function and promotes aging.
  • DNA damage activates inflammatory and secretory responses impacting tissue homeostasis.

Purpose of the Study:

  • To explore how nuclear DNA damage responses activate cytoplasmic pathways.
  • To understand the link between DNA damage, secretory phenotypes, and organismal aging.

Main Methods:

  • Review of recent evidence on DNA damage response pathways.
  • Analysis of non-cell-autonomous responses to genomic instability.

Main Results:

  • DNA damage triggers inflammatory cytokines, damage-associated molecular patterns, and extracellular vesicles.
  • Chronic activation of these responses contributes to tissue degeneration and systemic decline.

Conclusions:

  • Targeting DNA damage mechanisms can mitigate harmful systemic responses.
  • Interventions may preserve regeneration and immune surveillance, potentially delaying aging.