Conclusions:
Overall, our work confirms the association between UCP3 variability and muscular strength measured through handgrip, also in the Danish population. Despite the differences in handgrip performances found in nonagenarians and individuals aged 50+ across Europe (Jeune et al., 2006; Andersen-Ranberg et al., 2009), UCP3 genetic polymorphisms could be considered a common and informative target for better evaluating muscular functionality and then the quality of aging in both northern and southern European populations. Furthermore, the different associations found between UCP3 polymorphism in individuals belonging to different age ranges may be due to the fact that UCP proteins act in a complex pathway where genetic variability may also interact with several transcription/replication factors directly regulating mitochondrial metabolism involved in muscular functioning. The coordination of these factors into a program responsive to the environment is complex and may represent one of the mechanisms used by the aging organism to adapt itself to the new physiological scenario (Franceschi et al., 2000). In line with this hypothesis are recent data emphasizing the role of UCP variations on metabolic efficiency (Mookerjee et al., 2010), which underline how the impact of UCP gene variation on human longevity can be due to the coordination of their different functions rather than the sole well-known effect on oxidative stress. In any case, our work adds a piece of evidence to the hypothesis that the variability of the UCP3 gene, involved in the control of energetic metabolism, can influence survival at old age. In general, the association of UCP genetic variability with survival, if confirmed in different populations by future replication studies, suggests a crucial role of their metabolic pathway in human longevity.

Acknowledgments:
This study was supported by the Max-Planck Institute for Demographic Research (Rostock, Germany), the National Institute on Aging (P01 AG08761), The Novo Nordisk Foundation, the Aase and Ejnar Danielsen Foundation, the Augustinus Foundation, the Brdrene Hartmann Foundation, the King Christian the 10th Foundation and the Einer Willumsens Mindelegat Foundation. The Danish Aging Research Center is supported by a grant from the VELUX Foundation. Researchers from University of Calabria were supported by the European Union Seventh Framework Programme (FP7/2007-2011) under grant agreement no. 259679.

Appendix A. Supplementary data:
Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.mad.2012.06.004.

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