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Determining the role of mutation load in mammalian senescence

2016-12-31
Somel, Mehmet
Kılınç, Gülşah Merve
Özer, Füsun
Turan, Zeliha Gözde
Koptekin, Dilek
Ghalichi, Ayshin
In most multicellular species, aging is accompanied by an increasing risk of disease and mortality, a process termed senescence. The evolutionary causes and genetic bases of senescence are little understood. Senescence is usually associated with accumulating cellular damage, although a number of theories suggest that harmful mutations that are expressed only at late age could also contribute to the aging phenotype. Analyzing primate brain transcriptome data, we recently identified a pattern that would support this latter notion: genes expressed at high levels in old individuals, compared to genes expressed at high levels in young adults, tend to be evolutionarily less conserved, suggesting that they might harbor a higher proportion of deleterious mutations. This result suggests that a deleterious mutation load may indeed play a role in senescence. In this project, we will use a wide array of transcriptome datasets across multiple tissues and mammalian species, to identify the generality of this pattern. Using a new metric, for the first time, we will measure the decrease in negative selection pressure with age. The results will shed light into one highly debated mechanism of senescence.