Aging of cell membranes: facts and theories.

This chapter is intended to outline the main results of a research trend realized by the author during the last 45 years, focused on the main role played by the cell membrane in the aging process. It is a very wide field; therefore, the reader cannot expect in this limited space a detailed description, but will be given a wide, interdisciplinary insight into the main facts and theories regarding cellular aging. The central idea described here is the concept called the membrane hypothesis of aging (MHA). The history, the chemical roots, physicochemical facts, biophysical processes, as well as the obligatory biochemical consequences are all touched in by indicating the most important sources of detailed knowledge for those who are more interested in the basic biology of the aging process. This chapter covers also the available anti-aging interventions on the cell membrane by means of the centrophenoxine treatment based on the MHA. It also briefly interprets the possibilities of a just developing anti-aging method by using the recombinant human growth hormone, essential basis of which is the species specificity, and the general presence of receptors of this hormone in the plasma membrane of all types of cells.

Is consensus in anti-aging medical intervention an elusive expectation or a realistic goal?

One of the biggest scandals of the recent history of medicine is the conflict of views between the gerontological establishment and the American Academy of Anti-Aging Medicine (A4M). The style used in that discussion was really rough and unusual. On the one hand, according to some representatives of the American Medical Associations (AMA), the use of human growth hormone (hGH) for anti-aging medical interventions is illegal, criminal, and requires persecution. On the other hand, A4M is of the opinion that all this is "...filled with incorrect, misplaced references and studies, and multiple basic scientific errors, in an apparent attempt to damage the anti-aging medical profession...". It is evident that in the frame of a short article is impossible to treat all the relevant aspects of this complicated story. Nevertheless, this Editorial attempts to point out the main results obtained so far, together with the most important issues of theoretical feasibility of the hGH replacement therapy (hGHRT). The comprehensive explanation of the aging process called "membrane hypothesis of aging" (MHA) offers a solid basis for the interpretation of the observed beneficial effects of the hGH through its practically ubiquitous membrane receptors, and the species specificity of this peptide hormone. The specific activation of these receptors stimulates the membrane transport functions, rehydrates the intracellular colloids, allowing to speed up the protein synthesis and turnover, and activates a great number of cellular functions, all observed so far. The facts known about the adult growth hormone deficiency (AGHD) syndrome, and the beneficial effects of hGHRT in all aspects of this pathology suggest that aging may generally be considered as an AGHD syndrome. If this concept is accepted by most of the gerontologists, we can resolve practically all problems involved in the above outlined controversies. All this requires an independent, open-minded approach to the problem, and pushes us to a better understanding of the results of theoretical aging research. This approach may open a new, realistic way to the development of efficient anti-aging medical interventions.

Fritz Verzár was born 120 years ago: a personal account.

Fritz Verzár, founder and one of the most important operator of experimental gerontology, was born 120 years ago at Budapest (Hungary) and passed away in 1979 at Basel (Switzerland) at the age of 93. This short paper, as well as the following one in this issue by Robert [Robert, L., 2006. Fritz Verzár was born 120 years ago: his contribution to experimental gerontology through the collagen research as assessed after half a century. Arch. Gerontol. Geriatr. 43, 13-43], intends to commemorate his human and scientific merits, which remained valid even after long decades after his death. The author of this paper was the last Hungarian pupil of Verzár; therefore, a personal touch of this commemoration could not be avoided and was not even wanted. Verzár was an exceptionally clever and realistic scientist and at the same time, a warm-hearted and honest man, who is remembered with deep respect and love.

Pharmacological interventions against aging through the cell plasma membrane: a review of the experimental results obtained in animals and humans.

As was shown in a recent review by this author (Ann. N.Y. Acad. Sci., 928: 187-199, 2001), oxyradicals cannot be considered only as harmful by-products of the oxidative metabolism, but living cells and organisms implicitly require their production. This idea is supported by numerous facts and arguments, the most important of which is that the complete inhibition of the oxyradical production by KCN (or by any block of respiration) kills the living organisms long before the energy reserves would be exhausted. This new theoretical approach not only helps our understanding of the normal functions of the living organisms, such as the basic memory mechanisms in the brain cells, but also helps in identifying the site-specific, radical-induced damaging mechanisms that represent the undesirable side effects of oxygen free radicals. First of all, these effects make the cell plasma membrane vulnerable and cause a series of intracellular functional disorders, as described by the membrane hypothesis of aging (MHA). The logical way for any antiaging intervention therefore should be to increase the available number of loosely bound electrons inside the plasma membrane that are easily accessible for OH(*) free radical scavenging. The present review summarizes the available knowledge regarding the theory of the use of membrane-related antiaging pharmaca, like centrophenoxine (CPH), tested in both animal experiments and human clinical trials. A modified, developed version of CPH coded as BCE-001 is also reported.

The biological waste product formation in the light of the membrane hypothesis of aging.

The membrane hypothesis of aging (MHA) explains the biological waste product (lipofuscin) formation as a disbalance between the rates of protein synthesis and damage, as well as of elimination of the damaged components. Although, this concept has not been refuted on the basis of any experimental evidence, it has neither been widely accepted. During the last decade the general interest has turned toward the molecular genetics so intensely, that research aimed at clarifying cell biological mechanisms became so to say hibernated. Nowadays it is being recognized more and more that after the complete description of the human genetic code, attention has to be dedicated again to the cellular mechanisms explaining the function of the gene products (proteins). In this context, our experimental findings described during the recent years may become again the subject of interest. We have shown that the in vivo inhibition of the lysosomal thiol-proteinase functions by sublethal doses of leupeptin in young, adult and old mice results in a considerable increase (about 30%) of the immobile fraction of membrane proteins in hepatocyte plasma membrane, meanwhile the lateral diffusion constant of the still mobile membrane proteins increased. These observations were interpreted as signs of a general slowing down of protein turnover in the plasma membrane, just by inhibiting the elimination mechanisms in the lysosomes. This paper will discuss the theoretical conclusions and significance of these findings for the biological waste product formation, as a basic cell biological function.