**7. Conclussion**

Gerontology has entered the 21 Century with significant empirical baggage but without a theory capable of generalising the data and discovering the general regularities of the aging process. Instead, as mentioned, more than 300 different theories have been developed. There is still no consistent opinion as to what the primary driving force of aging actually is. The majority of researchers are convinced that there are no genes for aging and that stochastic factors underlie the aging. Those who trust in the programmed theory assume that almost every process influencing aging is governed by its own genes, i.e. aging is multifactorial. According to this, genes of aging exist and they control the sole driving force of aging – proliferative-dependent bioenergetics decline. It can be shown that this programmed process underlies, whether expressly or by implication, any theory of aging based on real phenomenon. This can provide the basis for the creation of a united theory of aging.

The present situation in modern gerontology does not suggest any hope of the achievement of the abovementioned strategic aim: numerous efforts to elaborate a remedy for senescence based on stochastic theories have yielded no result. The strict restriction of food (calorie restriction) is the only trick that has been developed which authentically increases species' maximal lifespan. The mechanism for this phenomenon is not yet understood, but it is easily explained by the bioenergetics theory: the lack of food detains cell division which in turn leads to a lag of the proliferative clock relative to calendar time. The programmed theories do not much promise success because of the large number of genes that operate in the ageing process. A decrease in the level of bioenergetics is apparently programmed by only a few genes. The analysis of the evolutionary plasticity of fruit fly populations has shown that longevity is programmed by no more than by three genes (Mylnikov, 1997).

One relevant inference to be made of the theory stated above is that the manipulation of any secondary phenomenon generated by the decline in bioenergetics cannot give effect to an increase in the maximal lifespan. A means to operate bioenergetics has to be found - it is the only way towards healthy and unlimited longevity. This is complicated problem but it can be solved in the near future: the bioenergetics machine is already studied well enough, the regulator of energetical homeostasis is visible, and the potent arsenal of experimental techniques is created. The period depends mainly on facilities for research.

### **8. References**


Gerontology has entered the 21 Century with significant empirical baggage but without a theory capable of generalising the data and discovering the general regularities of the aging process. Instead, as mentioned, more than 300 different theories have been developed. There is still no consistent opinion as to what the primary driving force of aging actually is. The majority of researchers are convinced that there are no genes for aging and that stochastic factors underlie the aging. Those who trust in the programmed theory assume that almost every process influencing aging is governed by its own genes, i.e. aging is multifactorial. According to this, genes of aging exist and they control the sole driving force of aging – proliferative-dependent bioenergetics decline. It can be shown that this programmed process underlies, whether expressly or by implication, any theory of aging based on real phenomenon. This can provide the basis for the creation of a united

The present situation in modern gerontology does not suggest any hope of the achievement of the abovementioned strategic aim: numerous efforts to elaborate a remedy for senescence based on stochastic theories have yielded no result. The strict restriction of food (calorie restriction) is the only trick that has been developed which authentically increases species' maximal lifespan. The mechanism for this phenomenon is not yet understood, but it is easily explained by the bioenergetics theory: the lack of food detains cell division which in turn leads to a lag of the proliferative clock relative to calendar time. The programmed theories do not much promise success because of the large number of genes that operate in the ageing process. A decrease in the level of bioenergetics is apparently programmed by only a few genes. The analysis of the evolutionary plasticity of fruit fly populations has shown that longevity is programmed by no more than by three

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 *Spain* 

Sara Santa-Cruz Calvo,

**Sirtuin-Dependent Metabolic Control** 

 **and Its Role in the Aging Process** 

 *CIBERER- Instituto Carlos III. Carretera de Utrera Km. 1,Sevilla* 

During last years, the protein family of sirtuins, composed by NAD+-dependent deacetylases, has emerged as a key factor in aging. From yeast to humans, sirtuins are involved in metabolic changes that induce a higher respiratory capacity accompanied by lower oxidative damage. They are involved in the control of glucose catabolism, fatty acid metabolism, respiratory chain activity in mitochondria and several other metabolic processes including control of antioxidant capacity in cells and tissues (Dali-Youcef et al.,

As these deacetylases are dependent on the NAD+/NADH ratio, they can be considered as important sensors of the metabolic status of the cells and probably because this they are one of the main family of proteins involved in the regulation of metabolism in the cell (Li & Kazgan, 2011). Further, their relationship with the AMPK-dependent pathway, that controls respiratory metabolism by inhibiting insulin-dependent signaling, highlights the importance of these proteins in metabolic regulation and especially in insulin-resistance, diabetes and

Sirtuins have been involved in aging process and considered important factors in delaying aging process and increase longevity (Guarente, 2000; Tissenbaum & Guarente, 2001). However, very recent studies have questioned the role of these deacetylases in longevity (Burnett et al., 2011; Viswanathan & Guarente, 2011). But their activity in yeast, worms and flies still permits to correlate its function in metabolism and dietarydependent modulations with aging process (Guarente, 2008). However, to date, in mammals and, especially in humans, their role in longevity is not clear. Whereas in lower organisms only one member has been found, SIR2, in mammals, seven members have been described to date. This fact indicates a higher complexity in interactions, targets and functions in higher animals than in lowers. Further, in mammals, the specific distribution of these deacetylases among the different cell compartments also indicates several local-

2007; Elliott & Jirousek, 2008; Lomb et al., 2010; Pallas et al., 2008).

obesity (Canto et al., 2009; Ruderman et al., 2010).

dependent influences of sirtuins.

Corresponding Author

 \*

**1. Introduction** 

Plácido Navas and Guillermo López-Lluch\*

*Centro Andaluz de Biología del Desarrollo,* 

 *Universidad Pablo de Olavide-CSI,* 

