title: Analysis of cancer genomes reveals basic features of human aging and its role in cancer development.
abstract: Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer.
authors: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Dmitriy I
authors: DI
authors: Podolskiy
authors: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Alexei V
authors: AV
authors: Lobanov
authors: Broad Institute, Cambridge, Massachusetts 02142, USA.
authors: Gregory V
authors: GV
authors: Kryukov
authors: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.|Broad Institute, Cambridge, Massachusetts 02142, USA.
authors: Vadim N
authors: VN
authors: Gladyshev
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D000073359:Exome Sequencing / Q000379:methods; D055815:Young Adult