Interactions of aging and environmental agents: the gerontological perspective

This article attempts to briefly review the current status of knowledge of biogerontology as a basis for a beginning set of discussions on the potential roles of environmental agents in the modulation of rates of aging in man. The article has tried to summarize "what the toxicologist should know about gerontology," whereas a companion review, by Dr. Jerry Williams, summarizes "what the gerontologist should know about toxicity." The review begins by defining some basic terminology, including introduction of the term "gerontogens" for those putative environmental agents that may in fact modulate the times of onset and/or rates of development of specific aspects of the senescent phenotype. That phenotype is then briefly described from the level of populations to the level of molecules, including an organ systems approach with emphasis on what is observed in humans. Among the important points that emerge from this description are: the variety of phenotypic alterations; the multiplicity of phenotypic alterations in any one aged individual; the special vulnerability in humans of the arterial system; the loss of proliferative homeostasis; the decline in the efficiency of enzyme adaptation; the decline in protein synthesis; the increasing evidence of post-translational modifications of proteins and DNA; the evidence for chromosomal instability (and, therefore, the potential importance of environmental clastogens). Arguments for a genetic basis for differential rates of aging are then developed, and a number of "genotropic" theories of aging are tabulated (i.e., those theories that invoke crucial roles for alterations of the genomes of somatic cells, whether changes in gene expression, gene structure, or both). It is concluded that no single theory is supported by a preponderance of evidence. Because aging appears to involve numerous processes and is highly polygenic in its determination, it is likely that a number of different mechanisms are responsible for the phenotypic alterations and that different individuals exhibit various patterns of aging based upon their specific inheritance and environmental experiences. At this early stage in the development of experimental approaches to the study of environmental-genetic interactions in the genesis of different aspects of senescence, the most vital issue involves the question of suitable model systems. Clearly, a number of different model systems will be required. A selection of these is tabulated based upon their amenability to a reasonable degree of genetic definition and genetic manipulation. Only by controlling the genotype can the environmental influences be properly assessed.(ABSTRACT TRUNCATED AT 400 WORDS)