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Mice with reduced Myc function are healthier and live longer



DOI:10.1038/bonekey.2015.95

Increased expression of Myc, a highly conserved helix-loop-helix leucine zipper transcription factor, contributes to the development of many human cancers. Although knockout Myc mice are not viable, Hofmann et al. demonstrate that mice that are haploinsufficient for Myc, and so have a partial loss of Myc function, show significant benefits connected with longevity.

Not only do the mice have a longer lifespan compared to controls — male mice 10% longer and female mice 20% longer — they appear resistant to many of the diseases of ageing including loss of immune function, osteoporosis and cardiac fibrosis. Otherwise, the mice develop and reproduce normally.

Interestingly, the metabolic rate observed in Myc+/- mice was higher compared to controls of the same age and their serum levels of IGF-1 was consistently lower at all ages. However, the Myc hypomorphic phenotype did not appear to have any effect on the age-associated increase in DNA damage due to oxidative stress.

The most common cause of death in aged Myc+/- mice and in Myc+/+ controls was cancer, though decreased expression of Myc did appear to reduce the rate of cancer progression.

Editor's comment: Older Myc+/- mice exhibit lower body mass, lower serum IGF1 levels, less immunosenescence, and lower levels of serum and liver cholesterol, as well as an enhanced metabolic rate and neuromuscular performance. These are all characteristic of young animals.


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