Regulation of longevity depends on genetic and environmental factors. According to Svanborg, a Swedish geriatrician, over the last decades human life expectancy increased as well as the age at onset of fatal diseases. Nevertheless, autopsies of centenarians revealed the presence of several severe pathologies which could have killed them much earlier. Therefore, the emphasis is on regulation of resistance dependent on the expression of genes such as Sirtuins, mTOR pathway and others controlling body resistance. Only a small fraction (<1%) of centenarians live to become supercentenarians (110 years), indicating a limit of performance and resistance of the body. This limit can be interpreted as 'tinkering' of nature instead of producing masterpieces as suggested by F. Jacob. These facts and theories are described in this chapter.