Ageing: Dietary protection for genes

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Date: Sept. 15, 2016
From: Nature(Vol. 537, Issue 7620)
Publisher: Nature Publishing Group
Document Type: Article
Length: 1,320 words
Lexile Measure: 1550L

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Author(s): Junko Oshima (corresponding author) [1]; George M. Martin (corresponding author) [1]

The accumulation of DNA damage is an inevitable side effect of living, and is one of the main causes of cellular and organismal ageing. Compromised DNA repair leads to persistent DNA damage, causing age-related disorders and shortening lifespans. In humans, this can manifest as progeroid syndromes, in which children or adults age at a greatly accelerated rate. On page 427, Vermeij et al . [1] demonstrate that a relatively modest degree of dietary restriction can greatly increase the lifespans of two mouse models of these human syndromes.

The authors' mouse strains harbour mutations in genes involved in a DNA-repair process called nucleotide excision repair (NER). In one strain, a mutation reduces production of the protein ERCC1, which normally forms a complex with a DNA endonuclease enzyme to create DNA breaks and excise damaged sequences. ERCC1 mutations can cause three diseases in humans [2] -- the accelerated-ageing disorders Cockayne syndrome and XFE progeroid syndrome, and xeroderma pigmentosum, in which people are extremely sensitive to DNA damage by sunlight. In the other mouse strain, a mutation inhibits production of another DNA endonuclease, called XPG. Human XPG mutations can present as xeroderma pigmentosum and Cockayne syndrome [3].

It has previously been shown [4] that mice harbouring mutations in Ercc1 exhibit many of the metabolic responses to stress that are seen in healthy mice subjected to dietary restriction -- in both, biological pathways involved in physiological maintenance are enhanced at the expense of pathways involved in growth. This is thought to be a survival response that helps to protect NER-deficient mice. Vermeij et al . therefore investigated whether dietary restriction could enhance these protective responses in their animal models. Indeed, a 30% restriction led to a substantial increase in lifespan in both strains of mouse, as compared with siblings given unlimited access to food (those fed ad libitum ).

A weakness of many investigations into dietary restriction is their failure to carefully investigate physiological and structural...

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Gale Document Number: GALE|A463523268