Database research on anti-aging

Cycloastragenol is a molecule isolated from various species of Astragalus that is purported to have telomerase activation activity. A single in vitro study done in 2009 led to claims that cycloastragenol may activate telomerase.

Melatonin is a 100% vegetarian drug-free sleep aid for relief of occasional sleeplessness. Melatonin helps establish normal sleep patterns to promote a more restful, relaxing sleep, and better overall health. The body naturally produces melatonin and Vitamin B6 is essential for melatonin production.

Resveratrol is a polyphenol naturally found in the skin of red grapes, certain berries, and other plants. Recent research has shown that Resveratrol can support healthy cardiovascular function. Resveratrol is best known for its cellular anti-aging properties, as well as for its ability to promote a healthy response to biological stress.

Masoprocol is a potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils.

Is a coenzyme found in all living cells. The compound is a dinucleotide, because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamid. Nicotinamide adenine dinucleotide exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively. NAD participates in many redox reactions in cells, including glycolysis and most of those, the citric acid cycle of cellular respiration

Pantothenic acid (Vitamin B5) plays a role in the synthesis of hemoglobin, steroid hormones, neurotransmitters, and lipids. It is the most important component of coenzyme-A, which assists in several metabolic pathways and is necessary for the transfer of fats to and from cells. Pantothenic acid is only mildly acidic, but is often available in combination with calcium to neutralize its acidity and increase its storage stability.

G. Forgacs is one of the leading scientists in the Organ Printing Project. Considerable part of his papers is devoted to study of physical mechanisms which underlie biological self-organization, particularly — self-assembly of cell structures. Concept of tissue fluidity firstly proposed in the Malcolm Steinberg’s differential adhesion hypothesis was experimentally validated in G. Forgacs’s studies and became the molecular base for the bioprinting technology. 3d printing of living tissues became possible due to existence of tissue surface tension and the ability of the same cells to stick together into spherical structures, The special «ink» is used in 3d bioprinting — it contains microspheres with 10 — 40 thousands of cells. It is established that, when such 3d bioprinting is used, each type cells migrate at the appropriate place and build up tissues and organs, which forms are defined by the arrangement of matrix particles («biopaper»). Biocompatible matrices, which are used in bioengineering, generally show positive results. However, they can cause a set of undesirable problems, too. For example, matrix immunogenicity, degradation velocity and toxicity of the products, formation of the fibrous tissue during degradation, interaction with adjacent tissues etc. can influence the late fate of transplantation and directly affect biological functions of the bioengineered tissue. Properties of extracellular matrix are extremely critical in the modelling of vascular tissues. Creation of artificial blood vessels with small diameter, which have mechanical strength comparable to those of the native vessels, is still one of the most difficult problems of tissue engineering. To solve that problem, a new approach, where agarous bars were used as building blocks for the form filled with tissue spheroids or cylinders, was developed. Layer-by-layer arrangement of agarous bars and standard multicellular structures (spheroids and cylinders) enable precise regulation of the internal diameter, the wall thickness and the pattern of vessel branching. All the process, which includes removing of the agarous bars, is automated and enables to obtain one-layered, as well as two-layered blood vessels. Such approach has many advantages, and it makes it possible to prevent a lot of problems linked to the presence of exogenous materials. Since constructions obtained are made of cells only, high cell density can be achieved. So the properties of such bioengineered vessels came close to the properties of the naive ones. Moreover, when multicellular cylinders are used as a «bioink», the maturing time decrease and forms of the final structures become more accurate. The important achievement of G. Forgacs and colleagues is the use of bioprinting for reconstruction of frameless blood vessels that enables to obtain vessels of various diameter and shape necessary for transplantation. The next stage of bioprinting must be creation of complicated branched macro- and microvascular systems with the internal diameter from 300 mkm and the wall thickness from 100 mkm, which will be available for clinical implantation.

The major research area of O. Srivastava’s laboratory is the study on the role of cross-links in crystallin protein aggregation during aging and cataractogenesis. Cristallin is the joint name for a family of proteins found in the eye’s crystalline lens and cornea of human and other mammals. Crystallin consists of several individual proteins: αА- and αВ- crystallins are the chaperone proteins maintaining the structure of crystalline lens proteins, and consequently, lens transparency; γ-crystallin is the structural protein found in the lens. The purpose of the study was to determine in vitro cross-linking of gamma D-crystallin fragments alone and with alpha-, beta- and gamma-crystallins. Moreover, the scientists tried to ascertain the existence of covalent multimers of the polypeptide in vivo, and post-translational modifications in the three isoforms of the polypeptide. The study has shown that crystallin fragments are covalently crosslinked via non-disulfide bonding. The polypeptide also exhibited crosslinking with individual alpha-, beta-, and gamma-crystallins. Tryptophan and methionine oxidation are posttranslational modifications of the crystallin polypeptide. So gamma D-crystallin fragment is able to crosslink another fragments and stimulates oxidation of tryptophan and methionine residues. The scientists have found two types of multimers which appear in youth and keep on accumulating during aging. The first type consists of 8 different crystallins (αА, αB etc.). The second type shows the presence of filensin and phakinin proteins in addition to crystallin fragments. Crystallin fragments undergo post-translational modifications. It is found that during cataractogenesis, multimers are accumulating more intensively than in heathy people. Insoluble βA3/A1 and βB1 crystallin fragments were found in the lens of patients with cataract. Further study on different types of crystallin proteins and its modifications found in the crystalline lens is necessary to develop a new treatment for cataract.

It has been known long ago that inhibition of TOR enlarges life span of invertebrates, particularly yeasts, nematodes and fruit flies. However, it has remained undecided for a long time whether inhibition of TOR enlarges life span of mammals. In the experiments carried out by D. Harrison’s team, TOR was inhibited by rapamycin. Three groups of genetically heterogeneous mice were used in the study. It was found that the life span considerably increased in the mice of all three groups: females showed 14 % increase, while males showed 9 % rise. As far as we now know, inhibition of TOR activates macroautophagy. That study has shown for the first time that inhibition of TOR enlarges life span of mammals, not only that of invertebrates.

The major research area of prof. A. Ryazanov is signaling molecules and protein synthesis, and their connection to cell growth, differentiation and aging. The scientist examines certified medicines only. If compounds having positive effect on life extension are found, the researcher won’t have to certify them again as they are already used in clinical practice. Finding of this study have not been published yet. In the future, this scientific project will probably be expanded. Clinical and histological analysis, as well as postmortem examination will be conducted in order to reveal how different compounds affect pathogenesis of cancer and age-related diseases. At the moment, A. Ryazanov leads the project on the large-scale screening of more than a thousand of medicines allowing to analyze their life extension effect in mice.