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Wiedemann-Rautenstrauch syndrome (neonatal progeroid syndrome) is an ultra-orphan disease from the group of premature aging syndromes with an autosomal recessive type of inheritance associated with mutations in the POLR3A, POLR3B, and POLR3GL genes encoding RNA polymerase III. The incidence of the disease is currently unknown. We present the first clinical description in Russian Federation of a patient 7 years 6 months old with Wiedemann-Rautenstrauch syndrome (compound heterozygous mutations in POLR3A gene) with progeroid features, adentia, growth retardation (height SDS -3,41, height velocity SDS -2,47), underweight (BMI SDS -6,20), and generalized lipodystrophy. The article presents the observation of the patient for 1.5 years, the world experience of dynamic follow-up of patients with neonatal progeroid syndrome, differential diagnosis, as well as recommendations for the management of patients with this syndrome. Given the lack of specific treatment to date, patients are observed by a multidisciplinary team of physicians.

Well-known theories of aging suggest that a certain metabolic defect negatively affects vital activity of the cell, be it oxidative stress, the accumulation of lesions in DNA, the exhaustion of telomeres, or distorted epigenetic processes. The theory of aging considered in the review postulates that an accumulation of progerin on the inner side of the nuclear envelope underlies the above defects. Progerin is a defective precursor of the lamin A nuclear matrix protein in which the C-terminal cysteine, which is removed normally, is retained and modified with a hydrophobic oligoisoprene chain. Progerin molecules attach with their hydrophobic processes to the inner membrane of the nuclear envelope, pushing away the adjacent fibrils of the nuclear matrix and the chromatin periphery. This changes the morphology and shape of the nucleus and alters the properties of the nuclear envelope and pore complexes embedded in it. As progerin accumulates in the nucleus, structural distortions increase in the nucleus, further distorting the nuclear-cytoplasmic transport of macromolecules and leading to the above defects in cell metabolism. This leads to increasing cell death and aging of the body over time. This mechanism of aging has been identified in patients with Hutchinson-Gilford progeria syndrome (HGPS). Mass progerin production in HGPS is caused by the point mutation c.1824C→T in exon 11 of the LMNA gene, which codes for lamins A and C. The mutation stimulates non-standard splicing of the primary transcript during the formation of the lamin A precursor mRNA, thus causing progerin production. Children with progeria who have received the mutation from one of their parents age rapidly and die before 15 years of age. Approaches to progeria treatment are aimed at preventing the formation of progerin or destroying the progerin that has already accumulated. In the latter case, a promising strategy is to use rapamycin or its analogs and other substances and techniques that activate autophagy to purify the cell from progerin. Although in much smaller amounts, progerin is found in progeria-free people and may therefore play a role in natural aging. A maximum age that a person can reach is possible to estimate by taking account of the role that progerin plays in telomere shortening. Encouraging preliminary results achieved in purifying cells from progerin provide a means to develop an optimal procedure for periodic purification of the human body from progerin in order to reduce the rate of aging.

The action of natural (garlick extract, retinol) and of synthetic (crown-compound) antimutagenes in lymphotytes with gamma-radiation-induced inhibition of DNA-damages repair in cases of Elers-Danlos, syndrom, progeria and gomocystinurea was studied. Antimutagen cells defence from mutagenes was shown at all cases except one: progeria cells treated by retinol. Thus the repair-deficient cells resistance against mutagenes could be increased by antimutagenes.

The age dynamics of stable chromosome aberration (SCA) frequency was analysed by fluorescent in situ hybridization (FISH) in human blood lymphocytes derived from donors, irradiated by low doses of ionizing radiation (Chernobyl clean-up workers, nuclear weapon testers, etc.) and patients with hereditary premature aging--Werner's syndrome and Hutchinson-Gilford's syndrome. It was found that the level of SCA was age-dependent and increased in irradiated persons. So, the SCA level may be really an index of a so-called "radiation senescence", and may show a real biological age of irradiated persons. The patients with Werner's syndrome demonstrate increased SCA level in blood lymphocytes, corresponding to the premature aging of the organisms. But in the case of another form of premature aging--Hutchinson--Gilford's syndrome-- no rise of SCA level was found. Some possible reasons of such results are discussed.

Lymphoblastoid cell lines from patients with xeroderma pigmentosum (2 forms) and progeria (unusual form) were established using transformation of peripheral blood lymphocytes by Epstein--Barr virus. The influence of different UV doses on cell vitality, proliferation and cell cycle progression was studied by means of flow cytometry. The cell vitality was determined after incubation of cells with etidium bromide and FDA. We used cytograms with two logarithmic signals (log green/log red) to discriminate the cell cycle status. Cell cultures were used with density of 500,000 cells per 1 ml, previously synchronized at G-phase by the incubation in a medium with low serum content. The effect of UV irradiation was followed during 72 h. Among four analysed cell lines only line XP2SP demonstrated enhanced UV sensitivity, expressed by decreasing of the amount of living cells after the UV dose of 2.5 J/m2 and higher. The cell cycle studies showed that cells were blocked in S-phase and simultaneously the amount of apoptotic cells with both reduced DNA content and ability to bind FDA was seen increased. Similar events were observed in the control line only after the dose of 20 J/m2 and higher.