Biological aging is a common denominator for all living organisms, and yet we know relatively little about its mechanisms or how to control them. Studies on aging endocrine and nervous systems support the concept that modifications in neuroendocrine interactions can alter the time course of senescence. One hypothesis suggests that a plan for aging may be genetically encoded in the brain and expressed in a precisely scheduled time table of growth, maturation and aging. The platyfish (Xiphophorus maculatus) permits the study of how the genome controls the maturation of the brain-pituitary-gonadal (BPG) axis because intraspecific variation in the onset of its sexual maturation is due to genetic factors. Multiple alleles of the sex-linked locus P determine when the BPG axis becomes activated and maturation ensues. Depending on genotype, these events may occur at predictable periods anytime between 8 and 104 weeks of age. The objectives of this proposal are: (1) to study the structure, function and interaction of the brain, pituitary and gonad from sexual maturity to old age in male and female platyfish genetically determined to mature at different ages, maintained under controlled environmental and nutritional conditions, (2) to use """"""""genetically-engineered"""""""" fish to analyze separately the effects of sex, growth rate, population density and time of maturation on aging, (3) to understand how the P gene influences the aging of the BPG axis, (4) to determine if the time course of aging can be influenced by experimental manipulation. The questions we are posing in Xiphophorus are similar to those being asked in other vertebrates, including man. However, unlike other vertebrates, the platyfish presents us with a unique system in which to study the interaction of genetic and environmental factors on the senescence of the nervous and endocrine systems and on aging in general. The information derived may have more far-reaching implications in our comprehension of the genetic regulation of aging in the brain-endocrine axis.
