Romanian Gerovital H3 Injections and Gerovital H3 tablets by Ana Aslan

Thymic regrowth and reactivation of thymic endocrine activity may be achieved even in old animals by different endocrinological or nutritional manipulations such as,

(a) intrathymic transplantation of pineal gland or treatment with melatonin,

(b) implantation of a growth hormone (GH) secreting tumor cell line or treatment with exogenous GH,

(c) castration or treatment with exogenous luteinizing hormone-releasing hormone (LH-RH), (d) treatment with exogenous thyroxine or triiodothyronine, and

(e) nutritional interventions such as arginine or zinc supplementation.

These data strongly suggest that thymic involution is a phenomenon secondary to age-related alterations in neuroendocrine-thymus interactions and that it is the disruption of such interactions in old age that is responsible for age-associated dysfunction. With regard to the mechanisms involved in hormone-induced thymic reconstitution, it is at present, difficult to draw any definitive conclusions.

The effect of GH, thyroid hormones, and LH-RH may be due to the presence on thymic epithelial cells supposed to produce thymic peptides, of the specific hormone receptors. Melatonin or other pineal factors may also act through specific receptors, but experimental evidence is still lacking. The role of zinc, whose turnover is usually reduced in old age, is diverse. The effects range from the reactivation of zinc-dependent enzymes, required for both cell proliferation and apoptosis, to the reactivation of thymulin, a zinc-dependent thymic hormone. The role of zinc may even be more crucial.

According to recent preliminary data obtained both in animal and human studies, it appears that the above reported endocrinological manipulations capable of restoring thymic activity in old age, may act also by normalizing the altered zinc pool.

With advanced ageing the zinc pool undergoes progressive reduction as shown by the low zinc plasma levels and the negative crude zinc balance, both in humans and in rodents.

It has been suggested that such zinc deficiency might be involved in many age-related immunological dysfunctions, including thymic failure. The relevance of zinc for good functioning of the entire immune system is, at present, well documented. In particular, zinc is required to confer biological activity to one of the best-known thymic peptides, thymulin, which is responsible for cell-mediated immunity.

In deep zinc deficiencies, in humans and other animals, the low thymulin levels are due not to a primary failure of the thymus, but to a reduced peripheral saturation of thymic hormones by zinc ions. In aged mice both a reduced peripheral saturation of the hormone and a decreased production by the thymus were present. Oral zinc supplementation in old mice (22 months old) for 1 month induced a complete recovery of crude zinc balance from negative (−1.82) to positive values (+1.47), similar to those of young animals (+1.67). A full recovery of thymic functions with a regrowth of the organ and a partial restoration of the peripheral immune efficiency, as measured by mitogen responsiveness (PHA and ConA) and natural killer cell (NK) activity, were observed after zinc supplementation.

These findings clearly pin-point the relevance of zinc for immune efficiency and suggest that the age-related thymic involution and peripheral immunological dysfunctions are not intrinsic and irreversible events but are largely dependent on the altered zinc pool.

Previous work from this laboratory has demonstrated that both a trace element, zinc, and an amino acid, arginine, are capable, when orally administered, to recover some age-related immune dysfunctions.

In the present paper the effectiveness of a zinc-arginine combination versus the single nutrients in restoring age-related immunological alterations in old Balb/c mice has been investigated. The zinc-arginine combination is more effective than the treatments of single nutrients alone. In particular on the reactivation of thymic endocrine activity, as measured by the circulating level of one of the best known thymic factors, i.e. thymulin (Zn-FTS) and the natural killer (NK) cell activity, particularly under boosting condition by interleukin-2 (IL-2) or interferon (IFN). On the other parameters tested the zinc-arginine combination either was not more effective than the single nutrients or a prevalence of one of them was detectable, such as of arginine on mitogen response or of zinc on basal NK activity.

The findings clearly suggest that nutritional interventions and particularly combination of nutrients may represent an interesting and side-effect deprived approach for immunorestoration in elderly people.

Zinc is a relevant trace element for the efficiency of the entire immune system. The binding of zinc with some proteins, such as metallothioneins (MT) and α-2 macroglobulin (α-2M) is crucial for the immune efficiency during ageing and in age-related diseases, because these proteins may be involved in antagonistic pleiotropic effects. Indeed, the presence of chronic inflammation during ageing, generally, induces overexpression of these proteins that, due to their original biological function in fighting stressor agents, continuously sequester intracellular zinc.

As a consequence, a low zinc ion availability may appear in aged organisms leading to impairments of the immune response at thymic and extrathymic levels with the risk of the appearance of age-related diseases.

Therefore, MT and α-2M turn from protective in “young-adult age” to harmful agents in “ageing” following the basic assumption of an evolutionary theory of ageing, named the “antagonistic pleiotropy”, which suggests that a trade off between early beneficial effects and late negative outcomes can occur at a genetic and molecular level. On the other hand, some polymorphisms of MT (MT2A) and α-2M have been associated with atherosclerosis or Alzheimer disease, respectively. Physiological zinc supplementation in elderly restores the thymic endocrine activity and innate immune response (NK cell cytotoxicity) and increases the survival rate in old mice. Therefore, zinc supplementation is useful to achieve health longevity because these zinc-binding proteins may regain their original protective task against oxidative damage with, thus, a beneficial impact on immune response.

Zinc is an essential oligoelement for cell growth and cell survival and has been demonstrated to protect cells from oxidative stress induced by UVA or from genotoxic stress due to UVB.

In a recent work we demonstrated that the antioxidant role of zinc could be related to its ability to induce metallothioneins (MTs). In this study we identified the mechanism of zinc protection against solar-simulated light (SSL) injury.

Cultured human keratinocytes (HaCaT) were used to examine MTs expression and localization in response to solar-simulated radiation. We found translocation to the nucleus, with overexpression of MTs in irradiated cells, a novel observation.

The genoprotective effect of zinc was dependent on time and protein synthesis. DNA damage was significantly decreased after 48 h of ZnCl2 (100 μM) treatment and is inhibited by actinomycin D. ZnCl2 treatment (100 μM) led to an intense induction, redistribution, and accumulation of MT in the nucleus of irradiated cells. MT expression correlated with the time period of ZnCl2 treatment. CdCl2, a potent MT inducer, did not show any genoprotection, although the MTs were expressed in the nucleus. Overall our findings demonstrate that MTs could be a good candidate for explaining the genoprotection mediated by zinc on irradiated cells.

Infections can cause mortality when the immune system is damaged. The catalytic, structural (in zinc-finger proteins) and regulatory roles of zinc mean that this ion is involved in the maintenance of an effective immune response. Both zinc deficiency and impaired cell-mediated immunity combine during aging to result in increased susceptibility to infection. Dietary supplementation with the recommended daily allowance of zinc for between one and two months decreases the incidence of infection and increases the survival rate following infection in the elderly. This article reviews the biochemical pathways through which zinc might act to increase immunoresistance to infection in the elderly.