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Publication
Haploinsufficiency of the Myc regulator Mtbp extends survival and delays tumor
development in aging mice.
Authors Grieb BC, Boyd K, Mitra R, Eischen CM
Submitted By Submitted Externally on 12/2/2016
Status Published
Journal Aging
Year 2016
Date Published 10/1/2016
Volume : Pages 8 : 2590 - 2602
PubMed Reference 27803394
Abstract Alterations of specific genes can modulate aging. Myc, a transcription factor
that regulates the expression of many genes involved in critical cellular
functions was shown to have a role in controlling longevity. Decreased
expression of Myc inhibited many of the deleterious effects of aging and
increased lifespan in mice. Without altering Myc expression, reduced levels of
Mtbp, a recently identified regulator of Myc, limit Myc transcriptional activity
and proliferation, while increased levels promote Myc-mediated effects. To
determine the contribution of Mtbp to the effects of Myc on aging, we studied a
large cohort of Mtbp heterozygous mice and littermate matched wild-type
controls. Mtbp haploinsufficiency significantly increased longevity and maximal
survival in mice. Reduced levels of Mtbp did not alter locomotor activity,
litter size, or body size, but Mtbp heterozygous mice did exhibit elevated
markers of metabolism, particularly in the liver. Mtbp(+/-) mice also had a
significant delay in spontaneous cancer development, which was most prominent in
the hematopoietic system, and an altered tumor spectrum compared to Mtbp(+/+)
mice. Therefore, the data suggest Mtbp is a regulator of longevity in mice that
mimics some, but not all, of the properties of Myc in aging.




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