Adaptive Responses to Stress and Mortality Risk with Emphasis on Aging Rates

点击翻译按钮获取中文摘要

My laboratory seeks to understand why animals age at such different rates, what processes are associated with aging and how we can manipulate aging rates. Studying aging requires animals that have short lives. We developed crickets as a model of aging because young crickets resemble adults and eat similar food. Genes that impact aging in crickets are VERY similar in all animals. Crickets live about 120 days whereas the oldest human so far lived 122 years. We have extended the cricket lifespan to 257 days. We designed a multi-ingredient dietary formulation that extends longevity, reduces cancer and slows deterioration in the brains and bodies of aging mice. This treatment was designed to help five things associated with aging. These include 1) neutralizing the toxic byproducts generated by the tiny furnaces (called mitochondria) that make energy in all animal cells. These byproducts essentially cause "biological rusting;" 2) making the furnaces work better so they produce less toxins but still make enough energy to prevent the declines otherwise accompanying aging; 3) reducing excess activity of the immune system that can cause damage; 4) maintaining the actions of insulin (related to energy supply and diabetes); and 5) maintaining youthful cell membranes that transmit neuronal firing and transport food, O2, CO2 and waste in all animal cells. Cricket studies will help us derive an improved intervention that can serve as a research tool. Two things that strongly vary aging are growth and stress resistance. Moreover, these functions are antagonistic. Rapid growth reduces both stress resistance and life span whereas induction of stress resistance tends to slow growth and extend longevity. Long lived animals generally grow slower (e.g., slow-growing elephants and turtles versus fast growing mice and rabbits). We will examine how nutrition, plant chemicals, environmental toxins and radiation affect growth, stress resistance and aging in crickets. Besides measuring features like physical activity and memory (crickets learn!) we will measure changes in the body with age (e.g., hormones, energy supply, and damage) associated with stress resistance and health. We also found that processes that occur in early sleep promote growth (and aging) whereas stress resistance (and life support) are managed in late sleep. The fact that incompatible functions like growth and stress resistance are mainly active at different times means that the biological clock is highly relevant to aging. Thus, interventions to slow aging likely need to take the clock into account to be most effective. Our studies have potentially broad applications since all higher animals age (e.g., wildlife, livestock, zoo residents, pets, aquaculture). Because growth, stress resistance and aging are linked, results also have implications for managing exposure to stressors like radiation, pollution, plant toxins, and environmental extremes.**