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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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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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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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Studying Age-dependent Genomic Instability using the S. cerevisiae Chronological Lifespan Model
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Different responses to DNA damage determine ageing differences between organs.

Maria Vougioukalaki1, Joris Demmers1, Wilbert P Vermeij2

  • 1Department Molecular Genetics, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.

Aging Cell
|March 5, 2022
PubMed
Summary
This summary is machine-generated.

Organs possess distinct aging strategies. The intestine prioritizes cell death and stem cell plasticity, while the liver relies on DNA repair for sustained function, explaining varied aging.

Keywords:
DNA damage responseERCC1adult stem cellsgenome maintenancelivernucleotide excision repairorganoidssmall intestine

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Area of Science:

  • Genetics
  • Molecular Biology
  • Aging Research

Background:

  • Organ aging exhibits significant heterogeneity, contributing to multimorbidity.
  • The underlying mechanisms of organ-specific aging remain largely unknown.

Purpose of the Study:

  • To investigate the mechanisms of organ-specific aging.
  • To compare aging processes in the intestine and liver using a progeroid mouse model.

Main Methods:

  • Utilized Ercc1Δ/- mouse mutants, a model for accelerated aging.
  • Systematically compared intestine and liver at tissue, stem cell, and organoid levels.
  • Assessed apoptosis, proliferation, DNA repair markers (p21), and organoid-forming capacity.

Main Results:

  • Intestine showed minimal accelerated aging, with compensated stem cell loss and impaired organoid function.
  • Liver exhibited dramatic aging, increased apoptosis, polyploidization, and functionally exhausted stem cells.
  • Wild-type intestinal stem cells demonstrated inferior DNA repair compared to liver stem cells.

Conclusions:

  • Organs employ distinct anti-aging strategies: intestine favors apoptosis and stem cell plasticity, liver depends on robust DNA repair.
  • These organ-specific genome maintenance mechanisms explain heterogeneous aging and progeroid syndromes.