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Cited by 1Effects of Radiation ExposureGenetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and Senescence

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Spontaneous p53 activation in middle-aged C57BL/6 mice mitigates the lifespan-extending adaptive response induced by low-dose ionizing radiation

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Kohzaki, Masaoki, Suzuki, Keiji, Ootsuyama, Akira, Okazaki, Ryuji·2023·npj Aging
DOI 10.1038/s41514-023-00123-3PMC PMC10630390

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Abstract

Understanding the biological effects of low-dose (<100 mGy) ionizing radiation (LDR) is technically challenging. We investigated age-dependent LDR effects using adaptive response experiments in young (7-to 12-week-old) and middle-aged (40-to 62-week-old) C57BL/6 mice. Compared with 3 Gy irradiation, 0.02 Gy preirradiation followed by 3 Gy irradiation prolonged life in young mice but not middle-aged mice. Preirradiation also suppressed irradiation-induced 53BP1 repair foci in the small intestines, splenic apoptosis, and p53 activity in young mice but not middle-aged mice. Young p53 +/− C57BL/6 mice did not show these adaptive responses, indicating that insufficient p53 function in young mice mitigated the adaptive responses. Interestingly, p53 activation in middle-aged mice spontaneously became approximately 4.5-fold greater than that in young mice, possibly masking LDR stresses. Furthermore, adaptive responses in young mice, but not in middle-aged mice, suppressed some senescence-associated secretory phenotype (SASP) factors ( IL-6, CCL2 , CCL5 , CXCL1 ). Thus, LDR-induced adaptive responses associated with specific SASP factors may be attenuated by a combination of reduced DNA damage sensor/transducer function and chronic p53 activation in middle-aged mice.

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Metadata

Authors
Kohzaki, M., Suzuki, K., Ootsuyama, A., & Okazaki, R.
Affiliations
  • University of Occupational and Environmental Health Japan (JP)
  • Nagasaki University (JP)
Corresponding author
Kohzaki, Masaoki
ORCID
Venue
npj Aging
Publisher
Springer Science and Business Media LLC
Published
2023-11-07
Volume
9
Issue
1
Pages
26-26
ISSN
2731-6068 (ISSN-L)
DOI
10.1038/s41514-023-00123-3
PMC
PMC10630390
OpenAlex
W4388456034
Cited by
1
References
5
Citations by year
2024: 1
FWCI
0.16
Type
journal article
Language
en
Open access
Licence
Locations
  • npj Aging (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • GlaxoSmithKline Japan
  • University of Occupational and Environmental Health (031404)
  • Ministry of Education, Culture, Sports, Science and Technology (15K21565, 18K07774, 20K12172)
  • Research Promotion Foundation
  • Kaibara Morikazu Medical Science Promotion Foundation
  • Hitachi Global Foundation
  • Japan Society for the Promotion of Science (18K07774, 20K12172, 15K21565, 23K28231)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Keywords
low-dose radiation, adaptive radiation response, p53 activation, aging, lifespan extension, senescence-associated secretory phenotype, DNA damage response, apoptosis, interleukin-6, MCP-1, RANTES, CXCL1, C57BL/6 mice

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