correlate with Willett’s (2002) environmental trigger view of disease initiation. Nutrition Triggers for adverse and inappropriate nutritional practices in childhood have been shown to have psychosocial correlates in adult life with an increase in risk for disease (Jackson 2005). Obesity in humans, inﬂuenced by poor dietary choices and inactivity, are signiﬁcantly associated with an increased risk of chronic diseases such as diabetes, high blood pressure, high cholesterol, cardiovascular diseases, asthma, arthritis, some cancers and overall poor health status, that can signiﬁ- cantly decrease an individual’s life expectancy. CR is linked to nutritional choices. CR with nutritionally poor foods (eg, consuming half the quantity of a fast food) is still an unbalanced nutritional choice albeit in smaller portions and still provides no health advantage. Recently it was reported and further conﬁrmed, that a greater adherence to a traditional Mediterranean diet was associated with a signiﬁcant reduction in total all cause mor- tality (Trichopoulou et al 2003). Meyer and colleagues (2006) have demonstrated that associating a CR diet with adherence to a Mediterranean type diet that consisted of whole grains, beans, ﬁsh, fruit, olive oil, and many different kinds of veg- etables was beneﬁcial for heart health. Hence when optimal nutritional choices are coupled to CR, an increase in life expectancy is made possible. Such nutritional practices can serve to further expand the human life span. Caloric restriction (CR) Optimizing nutrition relates food intake to the beneﬁts of prudent CR. That is, CR refers to a dietary regimen low in calories without under nutrition that leads to increased disease risk due to nutritional deﬁcits. Following the pio- neering work of McCay and Maynard (1935) over 70 years ago, CR was then ﬁrst noted to signiﬁcantly extend the life span of rodents. Since that time, the increase in longevity has been demonstrated to result from the limitation of total calories derived from carbohydrates, fats, or proteins to a level 25%–60% below that of control animals that were fed ad libitum (Sohal and Weindruch 1996; Weindruch and Sohal 1997; Weindruch et al 2001). The extension in lifespan can approach 50% in rodents (Figure 2) (McCay et al 1935; Holloszt 1997). Moreover, CR has been shown to extend the lifespan in a broad range of organisms that include, yeast, rotifers, spiders, worms, ﬁsh, mice, and rats (Weindruch et al 2001). Emerging data show that its effect may also apply to non human primates (Lane et al 2001). Also Clinical Interventions in Aging 2007:2(4) Scientiﬁc interventions for anti-aging CR has been reported to delay a wide spectrum of diseases in different experimental animals such as kidney disease (Lane et al 2001), a variety of neoplasias (Fernandes et al 1976; Fernandes and Good 1984; Kubo et al 1984), autoim- mune disease (Sarkar et al 1982; Engelman et al 1990) and diabetes (Shields et al 1991), and it reduces age associated neuronal loss in most mouse models of neurodegenerative disorders such as Parkinson’s Disease (Duan and Mattson 1999) and Alzheimer’s Disease (Zhu et al 1999). The CR regimen also prevents age-associated declines in psychomo- tor and spatial memory tasks (Ingram et al 1997) and loss of dendritic spines necessary for learning (Moroi-Fetters et al 1989) and improves the brain’s plasticity and ability for self repair (Mattson 2000). Numerous biomarkers of CR have been identiﬁed in rodents, such as temperature, and DHEAS, insulin and glucose levels (Roth et al 2002). Roth and colleagues (2002) have recently observed that body temperature and insulin and DHEAS levels were also altered in primates that had been subjected to CR, hence validating the usefulness of these biomarkers in longer-lived species. More importantly, they have also shown that these parameters were altered in longer-lived men. Together these ﬁndings support the role these factors have as biomarkers of longevity in humans. Recently, a trial on the effect of a 6 month CR diet on metabolic biomarkers such as energy expenditure, and oxidative stress in humans was completed (Heilbronn et al 2006). The report showed that prolonged CR signiﬁcantly reduced two biomarkers of longevity, namely, fasting insulin level and body temperature. This is the ﬁrst human study to show that CR, in addition to signiﬁcant reductions in well known biomarkers of aging, also caused a metabolic adapta- tion in CR individuals and a reduction in DNA fragmentation that reﬂected less DNA damage (Heilbronn et al 2006). Important genetic links and regulators of organism life span have been uncovered in the form of sirtuins (Sauve et al 2006) Sirtuins are a family of NAD+ – dependent protein deacetylases widely distributed in all phyla of life. In multicel- lular organisms, sirtuins deacetylate histones and transcription factors that regulate stress, metabolism, and survival pathways. Sir2 is the founding member of a large and diverse family of these protein-modifying sirtuin enzymes, which regulate key pathways throughout biology, in eubacteria, archaea, eukaryotes, and even viruses (Sauve et al 2006). The link between CR and Sir2 and aging has been reviewed elsewhere (cf. for reviews: refer Sinclair and Guarente 1997; Guarente and Picard 2005; Suave et al 2006). We further point out that there is an extensive body of evidence that 539