IGF-1 can be manipulated to alter species longevity, and here researchers are starting to try tissue-specific alterations rather than global alterations: "Transgenic mice with low levels of global insulin-like growth factor-I (IGF-I) throughout their life span, including pre- and postnatal development, have increased longevity. This study investigated whether specific deficiency of liver-derived, endocrine IGF-I is of importance for life span. ... Liver-specific inactivation of the IGF-I gene was induced in mice at one month of age in most experiments. However, food intake, body composition, oxygen consumption at rest, and activity level were measured in mice that underwent inactivation of liver-derived IGF-I at 12 months of age. ... Serum IGF-I was reduced by approximately 80% in mice with adult, liver-specific IGF-I inactivation (LI-IGF-I-/- mice), and body weight decreased due to reduced body fat. The mean life span of LI-IGF-I-/- mice increased 10% vs. control mice ... Body weight and body fat decreased in LI-IGF-I-/- mice, possibly due to increased energy expenditure during exercise. Genes earlier reported to modulate stress response and collagen aging showed consistent regulation, providing mechanisms that could underlie the increased mean life span in the LI-IGF-I-/- mice."