Gene expression profiles associated with aging and mortality in humans.
We investigated the hypothesis that gene expression profiles in cultured cell lines from adults, aged 57-97 years, contain information about the biological age and potential longevity of the donors. We studied 104 unrelated grandparents from 31 Utah CEU (Centre d'Etude du Polymorphisme Humain - Utah) families, for whom lymphoblastoid cell lines were established in the 1980s. Combining publicly available gene expression data from these cell lines, and survival data from the Utah Population Database, we tested the relationship between expression of 2151 always-expressed genes, age, and survival of the donors. Approximately 16% of 2151 expression levels were associated with donor age: 10% decreased in expression with age, and 6% increased with age. Cell division cycle 42 (CDC42) and CORO1A exhibited strong associations both with age at draw and survival after draw (multiple comparisons-adjusted Monte Carlo P-value < 0.05). In general, gene expressions that increased with age were associated with increased mortality. Gene expressions that decreased with age were generally associated with reduced mortality. A multivariate estimate of biological age modeled from expression data was dominated by CDC42 expression, and was a significant predictor of survival after blood draw. A multivariate model of survival as a function of gene expression was dominated by CORO1A expression. This model accounted for approximately 23% of the variation in survival among the CEU grandparents. Some expression levels were negligibly associated with age in this cross-sectional dataset, but strongly associated with inter-individual differences in survival. These observations may lead to new insights regarding the genetic contribution to exceptional longevity.
Kerber
Richard A
RA
Department of Oncological Sciences, 2000 Circle of Hope, Salt Lake City, UT 84112-5550, USA. rich.kerber@louisville.edu
O'Brien
Elizabeth
E
Cawthon
Richard M
RM
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002460:Cell Line; D004781:Environmental Exposure; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D016016:Proportional Hazards Models