Johannes D. Veldhuis, MD


March 15, 2000

In This Article

Animal Models of Aging

The tortoise and lobster exhibit remarkably few features of aging, albeit for reasons not yet known. In fruit flies, the activation of the methuselah gene confers approximately a 30% extension of longevity. In the laboratory rat, neuronal sprouting can be stimulated by either apolipoprotein (Apo) E-3 or Apo E-4, whose production is increased by estrogen.[5] Apo-E transgenic knockout mice do not exhibit neurite outgrowth in response to estrogen. This finding may be pertinent to estrogen's presumed role in the prevention of neuronal aging and Alzheimer's disease. Estrogen also induces glial fibrillary acidic protein in astrocytes and their abutment and retraction from regulatory gamma-aminobutyric acid (GABA)-producing terminals that synapse on gonadotropin-releasing hormone (GnRH) neurons in the young female rat, but not in older animals that have lost the capacity to generate an LH surge. The important new experimental concept of defective hormone-sensitive neuronal plasticity with aging will require further experimental appraisal.[5]