deleterious to health and hence aging. Reports that show that in a wide spectrum of animal species, dietary antioxi- dants or caloric restriction, as well as chemical antioxidants or increased expression of antioxidant proteins, can lower mitochondria ROS production, which translates into an extension of the life span of these species which have served to support the free radical theory of aging (Orr and Sohal 1994; Sohal and Weindruck 1996; Parkes et al 1998; Sun and Tower 1999; Taub et al 1999; Schon 2000; Finkel and Holbrook 2000; Xu and Finkel 2002) However, it is known that ROS are generated in multiple cellular compartments and by multiple enzyme systems within the cell and have cellular signaling functions that are critical for the normal physiological function of the cell (Rhee et al 2003; Linnane et al 2007a, 2007b, 2007c). Important contributions to the production of ROS within cells, include proteins within the plasma membrane, such as the growing family of NADPH oxidases; lipid metabo- lism within the peroxisomes; protein synthesis within the endoplasmic reticulum; as well as the activity of various cytosolic enzymes such as the cyclo-oxygenases (Linnane and Eastwood 2004; Moldovan and Moldovan 2004; Balaban et al 2005). The generation of mitochondrial ROS is a consequence of oxidative phosphorylation, a process that uses the controlled and regulated oxidation of NADH or FADH to generate a potential energy for protons across the mitochondrial inner membrane (ROS produced by mito- chondria have been demonstrated to have important and speciﬁc roles in cellular signalling (Linnane and Eastwood 2004). The notion that the mitochondria are the sole most abundant site of ROS formation is currently an area of much discussion and debate (Rhee et al 2003; Balaban et al 2005; Linnane et al 2007b). The disruption of mitochondrial functions has been implicated in more than 40 known diseases, including ath- erosclerosis, ischemic heart disease, cancer, diabetes, and neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (cf. for reviews: McKenie 2004; Wallace 2005). Together these data indicate that mitochondrial health is an important factor for health and aging. Current and future research would aim to further improve and pre- serve mitochondrial function. Although further research is warranted, recent reports show that supplementation with coenzyme Q10 shows promise in maintaining the health of mitochondria (Kagan et al 1999; Crestanello et al 2002; McKenzie et al 2004; Somayagulu et al 2005; Linnane et al 2007b). Clinical Interventions in Aging 2007:2(4) Scientiﬁc interventions for anti-aging Further, mimetics of speciﬁc cellular antioxidants such as the SOD/catalase mimetic EUK-134 can be used to assist in reducing oxygen radicals and are already in clinical trials (Melov et al 2000). Hormones In humans there is a progressive decrease in hormone synthesis as well as a loss of hormone receptors with age. The elderly have demonstrated signiﬁcantly lower levels of production of most hormones compared to young adults (Hertogue 2005). There is a voluminous body of scientiﬁc literature concerned with hormonal deﬁcits with aging. That is, levels of growth hormone (GH) and insulin like growth factor-1 (IGF-1), melatonin (nocturnal), TSH, thyroid hormones (T3), calcitonin, DHEA (sulphated form in and its urinary 17-keto-metabolites), aldoste- rone, estrogens, testosterone in men and women have been demonstrated to progressively decrease with age in adults (for extensive review and individual references refer Hertogue 2005). Hormonal deﬁcits are not merely limited to menopause, andropause (male menopause), somatopause (adult growth hormone deﬁciency), and other sex hormone related diseases, they are now implicated in conditions such as obesity (Cranny et al 2006; Pasquali and Gambineri 2006), osteoporosis (Bennett 2005), ﬁbromyalgia (Cleare 2004) chronic fatigue syndrome (Cleare 2004) cancer (Simonenko et al 2006) attention deﬁcit problems (Cheng 2005) and possibly others as yet that remain to be elucidated. Conventional medicine treatments have only severed to address hormone depletion, ignoring the mild and moderate deﬁciencies; whereas the anti-aging medicine model focuses on mild, moderate, and severe deficiencies. Symptoms and severity of symptoms will be proportional to the level of deﬁciency for each hormone (Anton et al 2005). Only recently has the science of endocrinology started focusing on advanced testing methods, taking into account reference ranges based on age as well as gender, free or bioavailable hormone levels versus bound hormone levels, and ratios between major antagonistic hormones to titrate patients and achieve an optimum balance. Titration and optimum balance have been used with thyroid and insulin hormones, and has not been universally applied to all other hormones, till recent times. Ongoing research in the ﬁeld of longevity should include the use of nutrient and hormonal precursors to augment the body’s ability to make more of its own hormonal compounds thus limiting structural and DNA damage in the latter decades of life. 541