Cited by 16Genetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and SenescenceRedox biology and oxidative stress

Modelling the p53/p66Shc Aging Pathway in the Shortest Living Vertebrate Nothobranchius Furzeri

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Priami, Chiara, De Michele, Giulia, Cotelli, Franco, Cellerino, Alessandro, Giorgio, Marco, Pelicci, Pier Giuseppe, Migliaccio, Enrica·2015·Aging and Disease

Abstract

Oxidative stress induced by reactive oxygen species (ROS) increases during lifespan and is involved in aging processes. The p66Shc adaptor protein is a master regulator of oxidative stress response in mammals. Ablation of p66Shc enhances oxidative stress resistance both in vitro and in vivo. Most importantly, it has been demonstrated that its deletion retards aging in mice. Recently, new insights in the molecular mechanisms involving p66Shc and the p53 tumor suppressor genes were given: a specific p66Shc/p53 transcriptional regulation pathway was uncovered as determinant in oxidative stress response and, likely, in aging. p53, in a p66Shc-dependent manner, negatively downregulates the expression of 200 genes which are involved in the G2/M transition of mitotic cell cycle and are downregulated during physiological aging. p66Shc modulates the response of p53 by activating a p53 isoform (p44/p53, also named Delta40p53). Based on these latest results, several developments are expected in the future, as the generation of animal models to study aging and the evaluation of the use of the p53/p66Shc target genes as biomarkers in aging related diseases. The aim of this review is to investigate the conservation of the p66Shc and p53 role in oxidative stress between fish and mammals. We propose to approach this study trough a new model organism, the annual fish Nothobranchius furzeri, that has been demonstrated to develop typical signs of aging, like in mammals, including senescence, neurodegeneration, metabolic disorders and cancer.

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Authors
Priami, C., De Michele, G., Cotelli, F., Cellerino, A., Giorgio, M., Pelicci, P. G., & Migliaccio, E.
Affiliations
  • University of Milan (IT)
  • Scuola Normale Superiore (IT)
  • European Institute of Oncology (IT)
Venue
Aging and Disease
Published
2015
Volume
6
Issue
2
Pages
95
ISSN
2152-5250 (ISSN-L)
OpenAlex
W2034889054
Cited by
16
References
95
Citations by year
2026: 2 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 1
FWCI
0.23
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging and Disease (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Scuola Normale Superiore di Pisa (submittedVersion, other-oa)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
Funders
Associazione Italiana per la Ricerca sul Cancro
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
p53, p66Shc, aging, oxidative stress, reactive oxygen species, Nothobranchius furzeri, annual killifish, p53 isoforms, Δ40p53, transcriptional regulation, G2/M phase, senescence, neurodegeneration, aging biomarkers

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