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Living and Dying For Sex Fill box to show platform used: PC Macintosh A Theory of Aging Based on the Modulation of Cell Cycle Signaling by Reproductive Hormones Richard L. Bowen and Craig S. Atwood* HPG Axis is Analogous to the LeafApical Meristem Axis Development = differentiation Senescence = dysregulated growth and development. The Cost of Reproduction For similar sized organisms, longevity is inversely correlated with reproduction and growth rate (Williams, 1966). Lifespan (yrs.) Seeds (per yr) Growth (per yr) Yellow Poplar 200 30,000 2 feet Bristle Cone Pine 5000 few .01 inches Response Light (food) Deprived Water Temperature Leaf Growth Flower/Fruit Production Tree Growth Email: Conversely, in an environment of limited light, water and/or nutrient resources, phytochrome is downregulated. Examples of Hostile Reproductive Environments Decreasing Growth Rate and Increasing Longevity Nutrient Restriction Yellow Poplar (Magnoliaceae Liriodendron tulipifera) require increased energy expenditure which the animal perceives as a hostile reproductive environment. This chronic hostile environment (caloric restriction) decreases fertility by suppressing reproductive-cell cycle signaling factors. This preserves fertility and slows aging – awaiting a more friendly environment. Phone: Growth = cell division and endoreduplication Phone: Change = growth, development and senescence Cold - sub-arctic Bristle Cone Pine (Pinus longaeva) Climbing Plants Thorny Trees Climbing plants and thorny plants display exceptional longevity for their size. Based on this it has been proposed that avoidance of predation selects for a slower aging phenotype. SUMMARY The Reproductive-Cell Cycle Theory of Aging is able to explain: Why and how aging occurs in all sexually reproductive life forms including plants and unicellular organisms. Reproductive Hormones Drive Aging Via Regulation of Cell Proliferation and Differentiation Bonsai Plant (500 years) Dry climate Hostile reproductive environments such as cold, drought and lack of light restrict growth and fertility, and extend longevity. Mitogens – leaf hormones Gibberellins – promotes growth of new leaves, branches and fruit, lengthens stem; involved in flowering and fertilization. This is artificially achieved with the Bonsai tree since the cutting of leaves decreases “caloric intake” thereby restricting growth and fertility, and extending longevity. Cytokinins – stimulates cell division, promotes growth in lateral buds, blocks leaf senescence. Differentiative agents– peripheral hormones Auxins – promotes growth and elongation towards light, orients root and shoot growth, inhibits lateral bud growth, fosters growth of ovary walls for seeds, prevents abscission of leaves and fruit. Ethylene – promotes maturation, fruit ripening and abscission of leaves, flowers and fruits. Abscisic acid – inhibits growth and induces and maintains dormancy (required during extreme cold and darkness). The Jomon Cedar on Yakushima (7200 years old) Jarrah ( 500 years) Loss of reproductive function drives senescence Significant evidence in animals. “Reproduction is an all-important function of an organism's life history, and all other vital processes, including senescence and death, are shaped to serve it.” Thomas Axenrot The simultaneous regulation of the rate of aging and reproduction. How differing rates of reproduction between species is associated with differences in their lifespan. Why fasting extends longevity even though overall caloric intake is unchanged. Two phenomena that are closely related to species lifespan - the rate of growth and development and the ultimate size of the animal. The apparent paradox that size is directly proportional to lifespan and inversely proportional to fertility between species but vice versa within a species. CONCLUSION Since reproduction is the most important function of an organism, if reproductive-cell cycle signaling factors determine the rate of growth, determine the rate of development, determine the rate of reproduction, and determine the rate of senescence, then by definition they determine the rate of aging and thus lifespan. Printed for Research ShowCASE by Instructional Technology & Academic Computing (ITAC), 368-3777 Alt. Contact (Last, First): In summary, we propose that the hormones that regulate reproduction act in an antagonistic pleiotrophic manner to control aging via cell cycle signaling; promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence. The leaves act as a sensor of the environment, receiving and processing information, to appropriately regulate reproductive function. For example in an environment with plentiful light, water and nutrients, phytochrome signals for flowering. Metabolic and Reproductive Cost of Predator Avoidance, or “Working for Food” Decreases Reproduction and Extends Longevity We propose that some predation avoidance strategies Dept: A mechanistic understanding of aging has yet to be described; this paper puts forth a new theory that has the potential to explain aging in all sexually reproductive life forms. The theory also puts forth a new definition of aging - any change in an organism over time. This definition includes not only the changes associated with the loss of function (i.e. senescence, the commonly accepted definition of aging), but also the changes associated with the gain of function (growth and development). Using this definition, the rate of aging would be synonymous with the rate of change. The rate of change/aging is most rapid during the fetal period when organisms develop from a single cell at conception to a multicellular organism at birth. Therefore, “fetal aging” would be determined by factors regulating the rate of mitogenesis, differentiation, and cell death. We suggest these factors also are responsible for regulating aging throughout life. Thus, whatever controls mitogenesis and differentiation must also control aging. Since life-extending modalities consistently affect reproduction, and reproductive hormones are known to regulate mitogenesis and differentiation, we propose that aging is primarily regulated by the hormones that control reproduction (hence, the Reproductive-Cell Cycle Theory of Aging). In mammals, reproduction is controlled by hypothalamic-pituitary-gonadal (HPG) axis hormones. Longevity inducing interventions, including caloric restriction, decrease fertility by suppressing HPG axis hormones and HPG axis hormones are known to affect signaling through the welldocumented longevity regulating GH/IGF-1/PI3K/Akt/forkhead pathway. This is exemplified by genetic alterations in C. elegans where homologues of the HPG axis pathways, as well as the daf-2 and daf-9 pathways, all converge on daf-16, the homologue of human Forkhead that functions in the regulation of cell cycle events. Reproductive Friendly vs Reproductive Hostile Environ Aging Redefined - Change Over Time Name (Last, First): ABSTRACT Email: Voyager Pharmaceutical Corporation, Raleigh, N.C. and *Department of Medicine, University of Wisconsin, Madison, WI. On your proof: check one box & return to ITAC: OK Changes marked on proof; a disk with corrections is being submitted