IJMEG Copyright © 2010-present. All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Mol Epidemiol Genet 2010;1(3):214-225.

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

Key words: Ageing, longevity, sirtuin, SIRT1, SIRT3, SIRT4, genetic variation

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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