SIRT1 and Glucose intolerance: However, although moderate overexpression of SIRT1 protected against age-related diseases such as osteoporosis, glucose intolerance, and metabolic syndrome-related cancers, it did not extend lifespan.35 Thus, either SIRT1 has no role in regulating lifespan; or under the weak expression of the transgene (threefold) SIRT1 has no effect of longevity, and stronger expression of the transgene may be necessary to achieve lifespan extension.