Abstract

The limited proliferative potential of normal human cells in culture has provided an important model for the study of aging at the cellular level. The model has been validated by various data, including the fact that cells from individuals that exhibit premature aging have lower proliferative potential. Studies have clearly shown that cellular aging is due to active processes which result in inhibition of DNA synthesis and other changes in gene expression. When the processes that lead to cellular aging are disrupted, cells escape senescence and are able to divide indefinitely. This program project will take a molecular approach to the study of cellular aging. We will investigate the various changes in gene expression that occur as cells age in vitro, including those that lead to inhibition of DNA synthesis. We will also investigate the genetic defects that result in cellular immortalization and premature aging. This program is organized around four individual interacting scientific projects served by three cores, two technical and one administrative.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG007123-07
Application #
2049672
Study Section
Aging Review Committee (AGE)
Project Start
1987-09-01
Project End
1995-11-30
Budget Start
1993-12-01
Budget End
1994-11-30
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Duttaroy, A; Qian, J F; Smith, J S et al. (1997) Up-regulated P21CIP1 expression is part of the regulation quantitatively controlling serum deprivation-induced apoptosis. J Cell Biochem 64:434-46
Smith, J R; Nakanishi, M; Robetorye, R S et al. (1996) Studies demonstrating the complexity of regulation and action of the growth inhibitory gene SDI1. Exp Gerontol 31:327-35
Yang, L; Didenko, V V; Noda, A et al. (1995) Increased expression of p21Sdi1 in adrenocortical cells when they are placed in culture. Exp Cell Res 221:126-31
Kaul, S C; Wadhwa, R; Matsuda, Y et al. (1995) Mouse and human chromosomal assignments of mortalin, a novel member of the murine hsp70 family of proteins. FEBS Lett 361:269-72
Wadhwa, R; Pereira-Smith, O M; Reddel, R R et al. (1995) Correlation between complementation group for immortality and the cellular distribution of mortalin. Exp Cell Res 216:101-6
Nakanishi, M; Robetorye, R S; Pereira-Smith, O M et al. (1995) The C-terminal region of p21SDI1/WAF1/CIP1 is involved in proliferating cell nuclear antigen binding but does not appear to be required for growth inhibition. J Biol Chem 270:17060-3
Hensler, P J; Pereira-Smith, O M (1995) Human replicative senescence. A molecular study. Am J Pathol 147:1-8
Khaoustov, V I; Ozer, A; Smith, J R et al. (1995) Induction of senescent cell-derived inhibitor of DNA synthesis gene, SDI1, in hepatoblastoma (HepG2) cells arrested in the G2-phase of the cell cycle by 9-nitrocamptothecin. Lab Invest 73:118-27
Nakanishi, M; Robetorye, R S; Adami, G R et al. (1995) Identification of the active region of the DNA synthesis inhibitory gene p21Sdi1/CIP1/WAF1. EMBO J 14:555-63
Aggarwal, B B; Totpal, K; LaPushin, R et al. (1995) Diminished responsiveness of senescent normal human fibroblasts to TNF-dependent proliferation and interleukin production is not due to its effect on the receptors or on the activation of a nuclear factor NF-kappa B. Exp Cell Res 218:381-8

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