Other Projects
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T cell proliferation
Stress resistance

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This page summarizes some of the other projects now under way in the Miller laboratory, most of them still in an early phase.

1.  T cell proliferation in vivo

Several laboratories, including our own, have shown that aging leads to an increase in the proportion of T cells, particularly CD8 T cells, that are members of expanded clones expressing the same T cell receptor.  In addition, Marrack's laboratory has shown that T cells from old mice, but not from young mice, can proliferate when injected into non-irradiated young hosts.  Our current effort is focused on studying the identifying characteristics and functional properties of these unusual cells.  Work done here by Anavelys Ortiz-Suarez, a graduate student in the CMB program, has shown that CD8 cells capable of in vivo expansion are detectable in mice by 18 months of age, have unusually high levels of CD28, spontaneously produce IFNg, require IL-15 for in vivo expansion, and have the same defects in synapse formation observed in aged CD8 cells that do not have the ability to divide spontaneously in vivo.

2.  Stress resistance in mouse primary fibroblast cultures

Mutations in worms and flies that lead to increased life span very often also endow these invertebrates with high levels of resistance to several forms of cellular stress, including ultraviolet irradiation, heat exposure, and oxidation stress.  To see if mutations that increase mouse longevity also lead to cellular stress resistance, we are testing the resistance of primary skin-derived fibroblast cultures to in vitro stresses.  This study has several goals:

  • To see if resistance to one form of stress is linked to resistance to multiple stressors
  • To see if long-lived mice within a segregating population typically produce stress-resistant cells
  • To see if stress resistance in one kind of cell (e.g. fibroblasts) implies stress resistance in multiple cell types (e.g. hepatocytes, lymphocytes)
  • To map the genes that influence stress resistance
  • To see if non-genetic manipulations, such as caloric restriction and methionine restriction, also lead to stress resistance.

Results so far (see Murakami, Salmon, Miller, FASEB Journal, in press) show that fibroblasts from the skin of long-lived mutant dwarf mice are indeed resistant to multiple forms of stress, including UV light, heat, hydrogen peroxide, cadmium, and paraquat.