For humans and other animals, gender has an influence not only on their physical attributes, but also on life span. In humans, females have a longer life span than males. The reasons for this are not entirely clear. The role of gender in the regulation of longevity may be linked to gender specific genetic differences, including the expression of sex hormone patterns and the changes in these patterns during an individual's lifetime. In addition, the effect of sex hormones on other physiologic responses to environmental influences on cellular stress and oxidative damage may play a role in longevity. Gender can impact many disease states, including autoimmune diseases, and the factors that affect the development of autoimmune diseases and the regulation of longevity may share common mechanistic pathways. Other factors that may play a role include telomere and telomerase related differences, caloric restriction and changes in mitochondrial DNA. Inflammatory and regulatory pathways such as insulin/IGF signaling and Target of Rapamycin (TOR) signaling may also play a role in longevity and aging-related diseases such as Alzheimer's. The role of gender differences in the regulation of these pathways or factors is not entirely clear. The role of X-chromosome inactivation in longevity has also yet to be fully elucidated. Copyright © 2011 Elsevier B.V. All rights reserved.