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DNA damage responses and p53 in the aging process

Hui-Ling Ou and Björn Schumacher

Abstract

The genome is constantly attacked by genotoxic insults. DNA damage has long been established to cause cancer development through its mutagenic consequences. Conversely, DNA damage is induced during radiation- and chemotherapy to drive cells into apoptosis or senescence as outcomes of the DNA damage response (DDR). More recently, DNA damage has been recognized as a causal factor for the aging process. The causal role of DNA damage in aging and age-related diseases is illustrated by numerous congenital progeroid syndromes that are caused by mutations in genome maintenance pathways. The past two decades have brought rapid progress in the understanding of how DDR drives cancer development and causally contributes to the aging process. The DDR factor p53 turns out to not only take the centre stage during tumour development but also to play an important role in the aging process. Studies in metazoan models ranging from C. elegans to mammalian disease models have revealed cell autonomous and systemic DDR mechanisms that orchestrate adaptive responses that augment maintenance of the aging organism amid gradually accumulating DNA damage.

  • Submitted July 27, 2017.
  • Accepted September 1, 2017.