Functional Senescence: Genetic, cellular and biochemical basis of functional senescence Oxygen radicals cause damage to DNA, primarily to mitochondrial DNA and this damage can lead to mitochondrial dysfunction. It has been suggested that oxidative mitochondrial DNA and this damage can lead to mitochondrial dysfunction. It has been suggested that oxidative mitochondrial DNA damage is a major contributor to age-associated loss of brain function in the mouse. So far, caloric restriction-life span extension remains unknown. Preliminary studies using quantitative polymerase chain reaction show an age-associated increase in basal levels brain mitochondrial DNA damage. In addition, aged mice exhibit a lower repair capacity induction after induction of oxidative damage by the mitochondrial inhibitor 3-nitropropionic acid. The purpose of this pilot study is to determine if caloric restriction reduces oxidative DNA damage in mouse brain mitochondria and prevents further oxidative stress. The hypothesis predicts that caloric restriction will enhance the mitochondrial DNA repair capacity and therefore reduce the age-associated accumulation of mitochondrial DNA damage. To test this hypothesis the following aims will be addressed: 1) Determine the extent of mitochondrial DNA damage and repair in the brain during aging and caloric restriction in mice, 2) Examine the effect of caloric restriction on the induction of oxidative mitochondrial DNA damage by the mitochondrial inhibitor 3-nitropropionic acid, and 3) Examine mitochondrial function in caloric function in caloric mice. This pilot project will assist in laying the foundation for a research project directed towards the understanding of the effect of caloric restriction in the extension of mammalian life span.
| Acevedo-Torres, Karina; Berríos, Lexsy; Rosario, Nydia et al. (2009) Mitochondrial DNA damage is a hallmark of chemically induced and the R6/2 transgenic model of Huntington's disease. DNA Repair (Amst) 8:126-36 |
