Научное медицинское общество геронтологов и гериатров украины
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- Бұл бет үшін навигация:
- Roshina N. V., Symonenko A. V., Pasyukova E. G.
- Shilovsky G.A. 1 , Shram S.I. 2 , Khokhlov A.N. 1
Lemeshko Victor V.Escuela de Fisica, Facultad de Ciencias, Universidad Nacional de Colombia, sede Medellín, Calle 59-A, No 63-20, Medellin, Colombia vvasilie@unal.edu.co Apoptosis is defined as programmed cell death, and mitochondria, particularly their cytochrome c, play a crucial role in this process. Earlier, we discovered two populations of rat liver mitochondria with significantly different outer membrane integrity. During growth and development of the organism, the population of mitochondria with the fragile outer membrane replaced the other mitochondrial population with significantly more resistant outer membrane [Lemeshko, Biofizika, 1982, 37:837-840]. These results allowed us to suggest that the animal aging might be genetically programmed at the level of the outer membrane of mitochondria, through replacing of one population of mitochondria by the other, although both types of these organelles synthesize ATP well, as it was demonstrated in other our works. It means that the outer membrane permeabilization by the same internal and/or external environmental pro-apoptotic factors might be more probable in aged than in young organisms. The fundamental role of mitochondria in cell death has been finally recognized in 1998 [Susin et al., Mitochondria as regulator of apoptosis: doubt no more. Biochim Biophys Acta, 1998, 1366:151-165]. The “young” population of mitochondria, having the resistant outer membrane, seems to be needed to resist relatively high intensity of the free radical lipid peroxidation of biomembranes in young animals that we considered as important physiological factor allowing fast remodeling of biomembranes in young animals, allowing their growth and development. Although oxidative stress and reactive oxygen substances are widely recognized as pro-aging factors, our results clearly demonstrated that the cell antioxidant enzyme system has a low activity in young animals and significantly increases with age of rats up to half of the lifespan, thus leading to a decrease of free radical processes at this age period. Some subsequent decrease in the activity of the antioxidant enzyme system in aged animals, accompanied with relatively low rate of the membrane structure recovery, might be the fundamental basis for the development of degenerative diseases and even death events, as a result of increased population of “aged” mitochondria having fragile outer membrane. All these mean that not directly the death, but the probability of its realization under external environmental conditions is genetically programmed. A somewhat similar situation takes place at the cellular level that relates to the cytochrome c-mediated cell death. The release of cytochrome c from mitochondria under various pro-apoptotic factors, for example, does not yet mean cell death: as long as cytoplasmic reducing factors maintain cytochrome c in the reduced state, this hemoprotein is not yet pro-apoptotic. We recently demonstrated that only oxidized, but not reduced form of cytochrome c is capable to directly induce mitochondrial aggregation [Lemeshko, Mol.Cell. Biochem., 2012, 360:111-119], the process known as one of the attributes of apoptosis. In conclusion, we hypothesize that the probability of death of multicellular organisms is significantly contributed by genetically programmed structural and functional changes of various cells, like a change in mitochondrial populations, which increase the probability of multiple apoptotic processes. GENES CONTROLLING ASYMMETRIC NEUROBLAST DIVISION ARE INVOLVED IN DROSOPHILA MELANOGASTER LIFESPAN CONTROL Roshina N. V., Symonenko A. V., Pasyukova E. G.Institute of Molecular Genetics of RAS, Moscow, Russia egpas@rambler.ru Earlier, we demonstrated that several genes participating in regulation of the nervous system development are involved in lifespan control. An insertion of the P{GT1} vector 300 bp downstream of the structural part of escargot (esg) that encodes an RNA polymerase II transcription factor and insertions of P-based vectors in the structural part of aPRC that encodes atypical protein kinase C were associated with increase in male and female lifespan. Both esg and aPKC are involved in regulation of a crucial step in the nervous system development, asymmetric neuroblast division (AND). We suggested that other genes interacting with esg and aPKC during AND could be important for lifespan control. inscrutable (insc) is a gene essential for AND. We demonstrated that an insertion of the P{EPgy2} vector in the structural part of insc prolonged female lifespan. Analysis of lifespan of heterozygous esg and insc double mutants allowed us to predict that these genes interact in the course of lifespan determination. Decrease of esg transcription was shown to be associated with lifespan increase in mutant esg females and males. Mutant insc females with increased lifespan also demonstrated decrease in esg transcript amount. This result confirmed both interaction between esg and insc and association of prolonged lifespan with low esg expression. aPKC is directly phosphorylated by GSK3β (glycogen synthase kinase 3) encoded by shaggy (sgg), which further provides AND. We demonstrated that several insertions of P-based vectors in the structural part of sgg were associated with alterations of male and female lifespan. Altogether, our recent findings indicate that genes affecting AND during early steps of development could influence longevity of Drosophila adults. GERONTOLOGICAL ASPECTS OF NUCLEAR PROTEIN POSTTRANSLATIONAL MODIFICATIONS ON THE EXAMPLE OF POLY(ADP-RIBOSYL)ATION Shilovsky G.A.1, Shram S.I.2, Khokhlov A.N.11Evolutionary Cytogerontology Sector, School of Biology, Moscow State University, Moscow, Russia 2Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia gregory_sh@list.ru Various harmful genome modifications (mutations, unrepairable DNA damage, etc.) are known to accumulate with age. This leads to impairment of the genome functioning. The accumulation is due both to increased production of reactive oxygen species and reduction in antioxidant defense and DNA repair efficacy. At present, however, an important role in regulating of the genome stability is given also to epigenetic factors. In this regard, posttranslational modifications of chromatin-associated proteins are of special interest for molecular gerontology. The significance of this process is already shown, for example, for histone deacetylation. However, the role of poly(ADP-ribosyl)ation is less clear. This is one of the earliest cell responses to DNA damage catalyzed by a family of transferases – poly(ADP-ribose) polymerases (PARP). The most studied is the principal member of the family – PARP-1 (EC 2.4.2.30). Poly(ADP-ribosyl)ation is accompanied by a number of cellular processes, including DNA repair, replication and recombination, as well as apoptosis and necrosis. To understand PARP role in aging and lifespan determination, the data on changes of PARP activity and PARP-1 gene expression with age and in aging-associated diseases, with special attention given to the use of various molecular-genetic approaches (knockdown, knockout, etc.), are reviewed. Analysis of other researchers’ results and our own data demonstrates that PARP activity paradoxically decreases with age while the level of PARP-1 stays the same and the level of the PARP-activating DNA breaks increases. This might serve as a predictor of age-related pathologies and genomic instability, as well as a perspective marker of aging. Changes in the size and number of poly(ADP-ribose) chains as well as in the proportion and pattern of poly(ADP-ribosyl)ated nuclear proteins leading to impairment of their functioning are suggested as the possible reasons for the unusual change of PARP activity mentioned. INVESTIGATION OF POTENTIAL ANTI-AGING ACTIVITY OF OREGANO ESSENTIAL OIL IN CYTOGERONTOLOGICAL EXPERIMENTS жүктеу/скачать 2.61 Mb. Достарыңызбен бөлісу:
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