Evidence that mutation accumulation does not cause aging in <i>Saccharomyces cerevisiae</i>

Aging Cell - Tập 14 Số 3 - Trang 366-371 - 2015
Alaattin Kaya1, Alexei Lobanov1, Vadim N. Gladyshev1
1Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA

Tóm tắt

SummaryThe concept that mutations cause aging phenotypes could not be directly tested previously due to inability to identify age‐related mutations in somatic cells and determine their impact on organismal aging. Here, we subjected Saccharomyces cerevisiae to multiple rounds of replicative aging and assessed de novo mutations in daughters of mothers of different age. Mutations did increase with age, but their low numbers, < 1 per lifespan, excluded their causal role in aging. Structural genome changes also had no role. A mutant lacking thiol peroxidases had the mutation rate well above that of wild‐type cells, but this did not correspond to the aging pattern, as old wild‐type cells with few or no mutations were dying, whereas young mutant cells with many more mutations continued dividing. In addition, wild‐type cells lost mitochondrial DNA during aging, whereas shorter‐lived mutant cells preserved it, excluding a causal role of mitochondrial mutations in aging. Thus, DNA mutations do not cause aging in yeast. These findings may apply to other damage types, suggesting a causal role of cumulative damage, as opposed to individual damage types, in organismal aging.

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Tài liệu tham khảo

10.1073/pnas.90.17.7915

10.4161/cc.5.24.3565

10.1128/MMBR.67.3.376-399.2003

10.1007/978-94-007-2561-4_3

10.1093/nar/gkm1008

10.1007/978-94-007-2561-4_3

10.1073/pnas.97.15.8403

10.1111/j.1749-6632.1958.tb54674.x

10.1016/0027-5107(92)90042-Z

10.1073/pnas.1010721108

10.1371/journal.pgen.1000950

10.1016/j.tig.2013.05.004

10.1093/nar/gkm756

10.1093/geronj/11.3.298

10.1016/j.ceb.2008.09.004

10.1111/acel.12053

10.1101/gad.233221.113

10.1016/0921-8734(95)00018-2

10.1038/nature08981

10.1371/journal.pgen.0010069

10.1371/journal.pgen.0030084

10.1534/genetics.114.169243

10.1083/jcb.127.6.1985

10.1038/35041682

10.1002/bies.20723

10.1093/bioinformatics/btp324

10.1371/journal.pgen.1002015

10.1007/978-94-007-2561-4_5

10.1073/pnas.0803466105

10.1038/184956a0

10.1101/gr.107524.110

10.1126/science.1087706

10.1093/bioinformatics/btp666

10.1016/j.arr.2012.02.001

10.1111/1567-1364

10.1016/0165-1161(89)90001-0

10.1186/gb-2009-10-9-r98

10.1016/S0092-8674(00)80493-6

10.1146/annurev.cellbio.23.090506.123509

10.1073/pnas.45.1.30

10.1126/science.1204349

10.1534/genetics.114.168799

10.1016/j.cell.2009.04.014

10.1038/ng1988

10.1038/ng1618

10.1126/science.1170097

10.1016/j.exger.2009.03.001

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Aging Cell

Tập 14 Số 3

366-371

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