Anti Aging Compounds and Plant Extracts
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Aging is a progressive decline in the function and a decrease in the body’s ability to maintain homeostasis, it is associated with multiple physiological and pathological changes including formation of advanced glycation end products (AGEs) and free radicals damage leading to impairment of cell organelle's function and an increase in the susceptibility to disease of organ (Nanda et al., 2010; Dammann et al., 2012; Rolewska et al., 2012).
Several theories have been proposed to understand the aging process, one of the mechanisms underlying the aging process is the free radical theory, according to this theory aging is due to the accumulation of free radicals damage for unrepaired cellular components as a result of shift in the balance between the pro-oxidative and anti-oxidative processes in the direction of the pro-oxidative state (Bokov et al., 2004; Muller et al., 2007). The free radical and oxidative stress theory of aging is recognized as one of the most plausible and promising explanations for the process of aging and age-related diseases (Momtaz and Abdollahi, 2012). The free radical theory may also be used to explain many of the structural features that develop with ageing including the lipid peroxidation of membranes, formation of age pigments, cross-linkage of proteins, DNA damage and decline of mitochondrial function (Andrew, 2001).
D-Galactose has been used to induce oxidative stress in vivo to mimic natural aging (Lu et al., 2010; Chen et al., 2010). Overdose of D-gal can be catalyzed by aldose reductase into galactitol, which cannot be metabolized but will accumulate in the cell, leading to osmotic stress and generation of ROS and advanced glycation end products (Cui et al., 2006; Lu et al., 2007).
Mitochondrial dysfunction may be a principal underlying event in aging, their decay with age impairs cellular metabolism and leads to cellular decline. Oxidative mitochondrial DNA (mtDNA) lesions increase markedly with age, may be responsible for the age-associated increase in mtDNA mutations, its highly susceptible to damage that is induced by ROS because of its close proximity to the sites of ROS generation, its paucity of protective histones and its mutation is key players in aging and age related diseases (Druzhyna et al., 2008). The mtDNA4834-bp deletion (also known as the “common deletion”, CD) in rats is the most frequent aging associated occurrence of mtDNA damage. Therefore, CD has been used as a biomarker for aging (Meissner et al., 2008; Markaryan et al., 2009; Chen et al., 2010). The accumulation of mtDNA mutations was not associated with increased levels of oxidative stress, but it was correlated with the induction of apoptotic markers, which suggested that the accumulation of mtDNA mutations that promote apoptosis may be a central mechanism driving mammalian aging (Kujoth et al., 2006). MtDNA biogenesis is then promoted, as evidenced by increased mtDNA copy number (Suliman et al., 2003; Gutsaeva et al .,2006).
Aging is accompanied by the accumulation of 8-OHdG in nuclear DNA in different tissues. 8-hydroxy-2Ò†-deoxyguanosine (8-OHdG) is one of the most abundant oxidative products of DNA and represents a noninvasive and sensitive biomarker of oxidative stress (Lu et al., 2004 and Busuttil et al., 2007). Mitochondrial DNA copy number is a marker of mitochondrial damage and malfunctioning (Hou et al., 2013). MtDNA copy number is dependent on oxidative stress level, cell antioxidant capacity, and quality of mitochondria and mtDNA (Lee and Wei, 2005).
Iron accumulation in tissues may be the causative factor for the accumulated oxidative damage in senescent cells (Munoz et al., 2011; Dixon and Stockwell, 2014). Several studies have suggested a positive relationship between the loss of iron homeostasis, the accumulation of oxidative damage and cellular aging (Hofer et al., 2008; Xu et al., 2010).
Grape seeds extract has various biological properties including antiaging, antioxidants, antibacterial, antiviral, anti-inflammatory, anti-allergic, and vasodilatory actions (Alia et al., 2003; Balu et al., 2006; Abdelgawad et al., 2012). The incidence of free radical-induced lipid peroxidation and inhibited the accumulation of oxidative DNA damages in the central nervous tissue of aging rats reduced by grape seed extract (Balu et al., 2005; Spranger et al., 2008).
Green tea is rich with polyphenols compounds, mainly epigallocatechingallate (EGCG), epicatechin (EC), epigallocatechin (EGC) and epicatechingallate (ECG). EGCG, the major and most active component of green tea catechins, acts as an antioxidant (Weinreb et al., 2004), and have the ability to participate in vitamin E recycling (Nematalla et al., 2011). Several studies showed suppression action of green tea polyphenolic compounds against the risks of age-related diseases (Yan et al., 2012). Most recently GTE treatment was seen to be able to reverse the impairment in hepatic, cardiac and renal functions and reducing the non desirable aging associated biochemical markers impacts in rats (Shereen and Zaghloul, 2013).
Ginkgo biloba is antioxidant capacity and free radical scavenger properties which could contribute to its hepatic and neuroprotective anti-apoptotic activity, it showed to reverse age related decline of neurotransmitter systems, SOD and hydroxyl radical scavenging activity and acts as anti-aging (Chan et al., 2007; Schiborr et al., 2010). Ginkgo biloba have a protective action against the free radicals and peroxidations in liver fibrosis in aged rats (Huang et al., 2005).
Pomegranate fruit and seeds have free radical scavenging and antioxidant properties (Seeram et al., 2005; Soobrattee et al., 2005). Pomegranate has been used for centuries to confer health benefits in a number of inflammatory diseases, it has antioxidant, metal chelating, and ferric ion reducing and anti-glycation property, pomegranate fruit and seed potent therapy to delay or prevent onset of diabetes and aging complications (Kokila et al.,2010).
α-lipoic acid is a short chain of fatty acid containing two sulfur atoms. α-lipoic acid, a naturally occurring free radical scavenger and transition metal chelator is also one such antioxidant. It is well defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age (Shay et al., 2009).
Centrophenoxine is one of the potent antioxidants that reduce the peroxides formed in the tissues during aging, and has modulatory effects on most of the oxidants (Walvekar et al., 2008). Centrophenoxine (DMAE) is one of the anti-aging, neuroenergizing drugs (Zs-Nagy, 2002).
The working hypothesis of this study is to investigate the changes that occur in biomolecular and physiological biomarkers companied to natural and induced ageing, and to investigates the improvements role of some antiaging compounds and plant extracts including, grape seeds extract, green tea extract, ginkgo biloba extracts, pomegranate seeds extract, centrophenoxine and lipoic acid in slowing and delaying the natural and induced aging processes including, age associated complications at levels of oxidant-antioxidants biomarkers, changes in the mtDNA4834 deletion, oxidative products of DNA (8-OHdG) and mtDNA copy number in liver and brain tissues, accumulation total non-heme iron amounts and ferritin and hepatic, cardiac and renal function biomarkers.
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