With life span in the American population nearly doubling in the last century, it is becoming of greater importance both economically and socially, to understand the biological mechanisms allowing for healthy old age. Through a mechanistic understanding of the biological processes contributing to old age, methodology can be derived by which the increasingly older population of Americans is also an increasingly healthier population. The long-term objective of this research is to better understand the biochemical and genetic mechanisms of aging through investigation of a large mammal, Canis familiaris. The working hypothesis is that cellular and genetic differences between dog breeds with naturally and extremely diverse lifespan, define a link between genetic alterations, oxidative stress, and aging. Specifically, the aims will determine the cellular stress levels and types of stress that influence lifespan within the domestic dog. These determinations will rectify the paucity of information pertaining to stress resistance in a larger mammal, offering opportune insight into human stress resistance.
This aim will be completed by collecting primary dermal fibroblasts from a range of dogs of various breeds, and exposing them to known oxidative stressors. Measurement of stress resistance yields mechanistic insight into which breeds are susceptible or resistant. Analysis of gene expression patterns for stress responsive genes by RT- PCR is the second aim and will define breed specific expression differences and changes responsible for demonstrated response. This proposal and hypothesis will challenge the current status of aging research by defining mechanisms that have not been evaluated in higher mammals. This proposal targets evaluation of natural animal populations rather than the evaluation of inbred mouse strains, therefore challenging the current knowledge of oxidative stress and genetic differences'applicability to human medicine. Lastly, the experimental paradigm is designed and established to facilitate educational and training opportunities for undergraduate scientists anticipating pursuit of advanced degrees.
Although genetic factors are presumed to influence aging through stress resistance at the cellular as well as at the organism level, few genes have been definitively identified for aging in mammals. The proposed work will change the technical concepts currently utilized in aging research by introducing and applying a higher mammal for analysis. This type of analysis will drive the field of gerontology into translational medicine.
| Gilmore, Keiva M; Greer, Kimberly A (2015) Why is the dog an ideal model for aging research? Exp Gerontol 71:14-20 |
