• Moses, Robb (PI)
  • Darlington, Gretchen (PI)
  • Pereira-Smith, Olivia (PI)
  • Kleinsek, Don (PI)
  • Smith, James (PI)

Project: Research project

Project Details


We plan to make use of human and animal cell cultures in an
interdisciplinary study focused on the cellular and molecular
biology of aging. The long-range goals are to understand the
molecular processes that lead to age-related deteriorative
changes in humans. A major component of this study will be to
further understand the processes that lead to cellular senescence
in human diploid fibroblast cells. These studies will include
cloning and characterization of sequences that code for inhibitors
of DNA synthesis that are present in senescent human diploid
fibroblast cells and preliminary experiments to study the
mechanism of action of the senescence cell inhibitor. Other
studies will focus on the mechanisms of immortalization of human
diploid cells to understand what normal cell functions have been
modified in immortal cells and therefore are important in
controlling cell proliferation in senescent cells. Another
important aspect is to understand which coordinately expressed in
proliferating and nonproliferating states. Studies of the effect of
cell proliferation and cell quiescence per se on gene expression in
cells that do not senescent but do retain tissue-specific function
will attempt to elucidate this question. The role of mutagenesis
in aging will also be studied. This will be done by comparing the
rates of mutation in cells from patients exhibiting premature
aging and DNA repair defects with those from normal donors.
This project complements the others in the program project in
that it will use cells in culture to ask direct questions about the
mechanisms of aging in vivo.
Effective start/end date9/1/8711/30/96


  • National Institutes of Health


  • Medicine(all)


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