Aging is the phenotype resulting from accumulation of genetic, cellular, and molecular damages. Many factors have been identified as either the cause or consequence of agerelated decline in functions and repair mechanisms. The hypothalamus is the source and a target of many of these factors and hormones responsible for the overall homeostasis in the body. With advanced age, the sensitivity of the hypothalamus to various feedback signals begins to decline. In recent years, several aging-related genes have been identified and their signaling pathways elucidated. These gene products include mTOR, IKK-β/NF-κB complex, and HIF-1α, an important cellular survival signal. All of these activators/modulators of the aging process have also been identified in the hypothalamus and shown to play crucial roles in nutrient sensing, metabolic regulation, energy balance, reproductive function, and stress adaptation. This illustrates the central role of the hypothalamus in aging. Inside the mitochondria, succinate is one of the most prominent intermediates of the Krebs cycle. Succinate oxidation in mitochondria provides the most powerful energy output per unit time. Extra-mitochondrial succinate triggers a host of succinate receptor (SUCN1 or GPR91)-mediated signaling pathways in many peripheral tissues including the hypothalamus. One of the actions of succinate is to stabilize the hypoxia and cellular stress conditions by inducing the transcriptional regulator HIF-1α. Through these actions, it is hypothesized that succinate has the potential to restore the gradual but significant loss in functions associated with cellular senescence and systemic aging.

Clinical placebo-controlled study of Enerlit-Clima (bioactive succinate-based food additive) a showed positive effect of the preparation on general clinical and psychoemotional manifestations of the climacteric syndrome. A trend to an increase in estradiol level in early pathological climacteric and normalization of the endometrial status were observed.

Unilateral ovariectomy (UOE) of female rats caused an increase in duration of the nonreproductive period (NRP) -metestrus and diestrus phases, and shortening of the reproductive period (RP) -proestrus and estrus phases of the estrous cycle (a symptom of hormonal deficiency). Signs of stress persisted 5 weeks after UOE: reduction of the ratio of thymus weight to the weight of adrenal glands (T/A). A twoweek course of the succinatecontaining composition with added B vitamins (SCCV) administered to the control female rats and those upon UOE has increased the T/A ratio as compared to that of intact animals, which is an indication of "activation" according to Garkavi et al. [1] and restored the NRP/RP ratio. Cytobiochemical analysis found a significant increase in nitroblue tetrazolium reduction during succinate oxidation in lymphocytes according to reading of animal blood smears.

The substrate composition containing succinic acid, substrates for succinate synthesis, and antioxidants increased the efficiency of pharmacotherapy in patients with coronary heart disease and hypertension. We revealed an increase in the quality of life and decrease in the functional class of heart failure, incidence of arrhythmias and exercise-related pain, and blood cholesterol concentration.

No abstract