Abstract

Genetic concepts and methodologies serve as the integrating themes for an analysis of several basic phenomena of importance to gerontology. I. A) An already well developed program of research on the in vitro clonal senescence of normal mammalian somatic cells will couple somatic cell genetic investigations with cell kinetic and biochemical analyses to determine the mechanisms limiting the replicative potentials of cultured normal cells and the contrasts in cell cycle regulation between normal cells, cells from patients with Werner syndrome, and neoplastic cells. B) The in vivo clonal senescence of normal hematopoietic cells will also be investigated. II. A newly emerging program of research involving the use of cultured mouse teratocarcinoma cells for the genetic analysis of in vivo aging will be expanded and will include efforts to carry out several types of interspecific gene transfers. III. A newly proposed program of comparative biogerontology, involving Mus musculus, Peromyscus leucopus and Notomys alexis will be coupled with I and II above and will be utilized for tests of the intrinsic mutagenesis and free-radical theories of aging.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG001751-12
Application #
3090590
Study Section
Aging Review Committee (AGE)
Project Start
1979-09-29
Project End
1991-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
12
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Basisty, Nathan B; Liu, Yuxin; Reynolds, Jason et al. (2018) Stable Isotope Labeling Reveals Novel Insights Into Ubiquitin-Mediated Protein Aggregation With Age, Calorie Restriction, and Rapamycin Treatment. J Gerontol A Biol Sci Med Sci 73:561-570
Kramer, Philip A; Duan, Jicheng; Gaffrey, Matthew J et al. (2018) Fatiguing contractions increase protein S-glutathionylation occupancy in mouse skeletal muscle. Redox Biol 17:367-376
Zhang, Huiliang; Gong, Guohua; Wang, Pei et al. (2018) Heart specific knockout of Ndufs4 ameliorates ischemia reperfusion injury. J Mol Cell Cardiol 123:38-45
Ge, Xuan; Ciol, Marcia A; Pettan-Brewer, Christina et al. (2017) Self-motivated and stress-response performance assays in mice are age-dependent. Exp Gerontol 91:1-4
Sweetwyne, Mariya T; Pippin, Jeffrey W; Eng, Diana G et al. (2017) The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age. Kidney Int 91:1126-1145
Liu, Sophia Z; Marcinek, David J (2017) Skeletal muscle bioenergetics in aging and heart failure. Heart Fail Rev 22:167-178
Kruse, Shane E; Karunadharma, Pabalu P; Basisty, Nathan et al. (2016) Age modifies respiratory complex I and protein homeostasis in a muscle type-specific manner. Aging Cell 15:89-99
Loeb, Lawrence A (2016) Human Cancers Express a Mutator Phenotype: Hypothesis, Origin, and Consequences. Cancer Res 76:2057-9
Chiao, Ying Ann; Kolwicz, Stephen C; Basisty, Nathan et al. (2016) Rapamycin transiently induces mitochondrial remodeling to reprogram energy metabolism in old hearts. Aging (Albany NY) 8:314-27
Campbell, Matthew D; Marcinek, David J (2016) Evaluation of in vivo mitochondrial bioenergetics in skeletal muscle using NMR and optical methods. Biochim Biophys Acta 1862:716-724

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