Genetic regulation of life span, metabolism, and body weight in Pohn, a new wild-derived mouse strain.

Quantitative trait loci (QTL) of longevity identified in human and mouse are significantly colocalized, suggesting that common mechanisms are involved. However, the limited number of strains that have been used in mouse longevity studies undermines the ability to identify longevity genes. We crossed C57BL/6J mice with a new wild-derived strain, Pohn, and identified two life span QTL-Ls1 and Ls2. Interestingly, homologous human longevity QTL colocalize with Ls1. We also defined new QTL for metabolic heat production and body weight. Both phenotypes are significantly correlated with life span. We found that large clone ratio, an in vitro indicator for cellular senescence, is not correlated with life span, suggesting that cell senescence and intrinsic aging are not always associated. Overall, by using Pohn mice, we identified new QTL for longevity-related traits, thus facilitating the exploration of the genetic regulation of aging.

[1]  Yu Wang,et al.  Field investigations on operational performance of a novel radiant floor heating equipment applied in a typical office building , 2021, Building Services Engineering Research and Technology.

[2]  Qingying Meng,et al.  Identification of genetic determinants of IGF‐1 levels and longevity among mouse inbred strains , 2010, Aging cell.

[3]  D. Kiel,et al.  A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[4]  R. Korstanje,et al.  Integrating human and rodent data to identify the genetic factors involved in chronic kidney disease. , 2010, Journal of the American Society of Nephrology : JASN.

[5]  Gary A. Churchill,et al.  A New Standard Genetic Map for the Laboratory Mouse , 2009, Genetics.

[6]  C. Bult,et al.  Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels , 2009, Aging cell.

[7]  Sarah L Burgess-Herbert,et al.  Practical Applications of the Bioinformatics Toolbox for Narrowing Quantitative Trait Loci , 2008, Genetics.

[8]  Y. Brandvain,et al.  PohnB6F1: a cross of wild and domestic mice that is a new model of extended female reproductive life span. , 2007, The journals of gerontology. Series A, Biological sciences and medical sciences.

[9]  P. Hanlon,et al.  Three-locus and four-locus QTL interactions influence mouse insulin-like growth factor-I. , 2006, Physiological genomics.

[10]  S. Austad,et al.  Altered growth characteristics of skin fibroblasts from wild‐derived mice, and genetic loci regulating fibroblast clone size , 2006, Aging cell.

[11]  G. Churchill,et al.  Quantitative trait locus analysis for obesity reveals multiple networks of interacting loci , 2006, Mammalian Genome.

[12]  B. Paigen,et al.  Bioinformatics toolbox for narrowing rodent quantitative trait loci. , 2005, Trends in genetics : TIG.

[13]  Xiaosong Wang,et al.  Genetics of variation in HDL cholesterol in humans and mice. , 2004, Circulation research.

[14]  A. J. Hulbert,et al.  Metabolic rate is not reduced by dietary-restriction or by lowered insulin/IGF-1 signalling and is not correlated with individual lifespan in Drosophila melanogaster , 2004, Experimental Gerontology.

[15]  P. Redman,et al.  Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer , 2004, Aging cell.

[16]  A. Yashin,et al.  Is early life body weight a predictor of longevity and tumor risk in rats? , 2004, Experimental Gerontology.

[17]  A. Galecki,et al.  Quantitative trait loci for insulin-like growth factor I, leptin, thyroxine, and corticosterone in genetically heterogeneous mice. , 2003, Physiological genomics.

[18]  Hao Wu,et al.  R/qtl: QTL Mapping in Experimental Crosses , 2003, Bioinform..

[19]  A. Galecki,et al.  Big mice die young: early life body weight predicts longevity in genetically heterogeneous mice , 2002, Aging cell.

[20]  T. Roderick,et al.  Maximum Life Spans in Mice are Extended by Wild Strain Alleles , 2001, Experimental biology and medicine.

[21]  G. Churchill,et al.  A statistical framework for quantitative trait mapping. , 2001, Genetics.

[22]  Richard A. Miller,et al.  Differential longevity in mouse stocks selected for early life growth trajectory. , 2000, The journals of gerontology. Series A, Biological sciences and medical sciences.

[23]  L Kruglyak,et al.  High-resolution genetic mapping of complex traits. , 1995, American journal of human genetics.

[24]  R. Doerge,et al.  Empirical threshold values for quantitative trait mapping. , 1994, Genetics.

[25]  R. Gelman,et al.  Murine chromosomal regions correlated with longevity. , 1988, Genetics.

[26]  R. Gelman,et al.  Traits that influence longevity in mice. , 1984, Genetics.

[27]  H. A. Lawson,et al.  Mouse Genetics , 1939, Science.

[28]  L. Peters,et al.  Mice as a mammalian model for research on the genetics of aging. , 2011, ILAR journal.

[29]  G A Churchill,et al.  Concordance of murine quantitative trait loci for salt-induced hypertension with rat and human loci. , 2001, Genomics.

[30]  D. Kiel,et al.  Bmc Medical Genetics Genetic Correlates of Longevity and Selected Age-related Phenotypes: a Genome-wide Association Study in the Framingham Study , 2022 .