David E Harrison

..Overall, by using Pohn mice, we identified new QTL for longevity-related traits, thus facilitating the exploration of the genetic regulation of aging...

..These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases...

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..Possibly, out-crossing Pohn mice unmasked cryptic alleles that promote extended female reproduction. This work establishes the PohnB6F1 hybrid as a new model for delayed reproductive aging...

..CONCLUSION: In B6 HSC development, LTRA is dissociated from expansion. Although 1 x 10(6) BMCs have much lower LTRA, they expand HSCs as well as 1 x 10(6) FLCs. HSC expansion is partly exhausted in BALB, but not B6, during development...

..This study tests how each mutation affects HSC function...

..CONCLUSIONS: Aged BALB mice show hematopoietic and HSC senescence and clonal succession. Lifelong DR slows hematopoietic senescence and prevents HSC aging...

..The other agents had no significant effects on life span. The use of UM-HET3 mice helps assure that these results are not the result of unresponsiveness of a single genotype but that they more broadly represent laboratory mice...

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..That DR increases or maintains stem-cell function with age, while decreasing cancer, has far-reaching health implications...

..In both BXD RI and B6SJLF2 mice, QTLs regulating B-cell proportions showed no significant effect on T-cell proportions and vice versa. Thus, PB B- and T-lymphocyte proportions are regulated separately by different genetic elements...

..These enzymes may protect Pohn TSFs from oxidation...

..The novel in vivo model of fetal myocardium in the kidney capsule appears to be valuable for testing repopulating abilities of potential cardiac progenitors...

..53, P < 0.01). These results support the hypothesis that the IGF1 pathway plays a key role in regulating longevity in mice and indicates that common genetic mechanisms may exist for regulating IGF1 levels and lifespan...

..These results demonstrate pituitary hormone withdrawal can extend life span even if these hormones are removed relatively late in life...

..Thus, WAT transplantation was effective for both prevention and therapy. In the future, WAT transplantation may become a useful alternative to hormone replacement in treating not only lipodystropy, but also certain types of obesity...

..CONCLUSION: The Trp53-null allele expands bone marrow Lin(-)Sca-1(+)c-kit(+)CD34(-) cells and the overall activity of HSCs; however, it increases recipient mortality...

..Thus, a reduced proportion of peripheral blood CD4(+) lymphocytes is a consistent ageing phenotype in a wide range of Mus musculus strains...

..Effects of DR that extend life spans in both normal control and ob/ob mice in this study are likely targets for interventions to retard aging and extend healthy lifespan in human beings. ..

..Understanding how reductions in function of the insulin and IGF-1 pathways delay aspects of mammalian aging may suggest treatments to improve health as human beings age. ..

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..The assays are feasible due to the genetic resources and animal expertise at The Jackson Laboratory, as well as the applicants' extensive experience in evaluating HSC functions. ..

..Understanding how reductions in function of the insulin and IGF-1 pathways delay aspects of mammalian aging may suggest treatments to improve health as human beings age. ..

..The primary training facility is TJL, a private, independent research center. TJL is an NIH Basic Cancer Research Center, raises 3 million mice annually, and has held NIH research training grants continuously since 1956...

..Results in these systems may suggest mechanisms by which the interventions retard aging. ..

..Results in these systems may suggest mechanisms by which the interventions retard aging. ..

..Understanding how reductions in function of the insulin and IGF-1 pathways delay aspects of mammalian aging may suggest treatments to improve health as human beings age. ..

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..abstract_text> ..

..As already shown for Leg1(a) and Leg2(a), alleles that extend maximum life spans by 10% or more can be detected. ..

..Candidate genes will be tested to see whether MOLD alleles differ from those of NZW, LP and BALB. The gene will ultimately be identified by homologous recombination. ..

..1 cM. Candidate genes will be tested in transgenics and ultimately identified by homologous recombination. ..

..Clinical use of cord blood often requires freezing. Effects of various freezing methods on PHSC function will be tested using genetically disparate cell types. ..

..Allophenics will be produced by fusing early CXB-12 embryos with F1 embryos, genetically marked to distinguish PHSC progeny. Identity, number and function of individual PHSC will be defined by competitive dilution. ..