Review Article The molecular genetics of sirtuins: association with human longevity and age-related diseases
Letizia Polito, Patrick G. Kehoe, Gianluigi Forloni, Diego Albani
Laboratory of Biology of Neurodegenerative Disorders, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy; Golgi Cenci Research Center, Abbiategrasso, Italy; Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Science at North Bristol, University of Bristol, Frenchay Hospital, Bristol BS16 1LE, UK.
Received June 1, 2010, accepted June 15, 2010, available online June 20, 2010
Abstract: The sirtuins are a family of proteins remarkably conserved from yeast to humans. In organisms such as yeast, worms and flies it is quite well established that the activity of sirtuins prolongs lifespan. As a result of promising findings in simple organisms, sirtuins are now investigated in higher organisms in relation to the ageing process. In mammals there are seven different sirtuin proteins each encoded by individual genes (SIRT1-7). Although sirtuins share a highly conserved catalytic domain, they differ in their biological function. Some mammalian sirtuins have been implicated in different ageing pathways and their modulation has been deemed to be beneficial in different models of age-associated diseases. Overall, sirtuins could contribute to mechanisms of human longevity and avoid or delay the onset of age-associated disorders. Here we review and discuss the potential impact of genetic variation in the sirtuin genes in relation to human longevity and age-related diseases.(IJMEG1006001).
Address all correspondence to: Letizia Polito, PhD Department of Neuroscience, Mario Negri Institute for Pharmacological Research Via La Masa 19, 20156 Milan, Italy Phone: +39 02 39014594 Fax: +39 02 3546277 E-mail: letizia.polito@marionegri.it