Increasing Protein Cisd2 Levels Extends Lifespan and Reduces Aging Increasing Protein Cisd2 Levels Extends Lifespan and Reduces Aging The Cisd2 gene is highly conserved among species. It encodes a protein that crosses the mitochondrial outer membrane and may be related to autophagy (cellular cleanup). It also maps to a region of human chromosome 4q that is linked with longevity. Researchers have previously shown that removing the cisd2 gene in transgenic mice results in shortened lifespan. They have also shown that levels of cisd2 decrease with age. In the current study, the same researchers developed a transgenic method that induces continued high level expression of cisd2 throughout life. They linked the gene to a special promoter that causes continued expression. They found that wild- type rats had a reduced expression of the gene by 37% at one year and 57% at two years. No reduction was observed in the transgenic animals. Importantly they found that the transgenic animals mean lifespan increased by 5 months and maximum lifespan increased 3.66 months in males, and 8.57 months (30%) in females. They also found there were no deleterious side effects. It was also shown that the csd2 expressing animals displayed decreased signs of mitochondrial, skin, muscle, and nerve cell aging. The authors provocatively conclude: the Cisd2 TG mouse results thus provide an experimental basis that will help the development of a regimen that may stimulate human CISD2 expression and/or activity in order to ameliorate age-associated phenotypes such as muscle and neuronal tissue degeneration and thus possibly extend the healthy lifespan of humans.