Contents of the review «Scientific trends of life extension»

 

 

Section 1. GENERAL ISSUES OF AGING

Evolution. Differences in life extension between species.
Non-aging species Insulin signalling plays a role in evolution of aging
Correlations between life extension and different physiological parameters in reptiles
Increase of life extension in modern society is inevitable
All known life strategies show instability against effects of aging
Rapid development at early stages results in accelerated aging
Artificial suppression of reproduction in fruit flies results in slowing down aging for next generations
Phenomenon of aging has far-reaching biodemographic consequences
Relationship between longevity in rodents and evolution of anti-cancer mechanisms has been established
Studies of naked mole rat showed that cell survivability and rate of aging could be influenced by changes resulting from protein denaturation
Search for differences in cellular and molecular mechanisms influencing rate of aging in different species

Differences in human life longevity
Extensive search for longevity genes
Search for biomarkers of longevity and identification of genes responsible for human life extension
Studies of oldest living people who avoided oncological and cardiovascular diseases
Search for longevity factors acting on early life stages of people
Role of food nutritive value restrictions and genes in human longevity has been confirmed

Section 2. SYSTEMATIC APPROACHES IN STUDIES OF AGING

Systems Biology of Aging
Development of network diagram of mechanisms of aging
Building of computer models of mechanisms of aging based on John Furber’s network diagram
Analysis of expression profiles of age-dependent genes of man, mouse and rat
Simulation of cell aging processes
Strategy of studies of aging and implementation in practice of data obtained
Strategy of reaching negligible aging by engineering methods
Aging is the most ancient phenomenon of evolution

Biomarkers of aging
«Stress gene» HSP-16.2 is offered as a biomarker of aging
Free radicals accumulate with aging
Level of growth hormone decreases with aging
Four proteins identified, which are activated with telomeres damage and associated with aging
Allostatic load can serve as a complex of biomarkers of aging
AGE accumulation can be considered as a biomarker of aging and age-dependent diseases
Level of interleukin-6 increases with aging

Search for geroprotectors
Biguanides demonstrate geroprotective abilities
Screening of medical drugs for determining their impact on mice life longevity Screening of chemical substances for determining their impact on mice life longevity

Section 3. STUDIES OF AGING AT CELLULAR LEVEL

Regulation of cell cycle, role of replicative aging Discovery of chromosome protection mechanism has been awarded with Nobel Prize Protein kinase inhibitor ð38 prevents accelerated cell aging at Werner syndrome Discovery of mechanism of alternative telomere elongation without telomerase participation Smoking and obesity result in telomere shortening Infection provokes telomere shortening “Shelterin” component of protein complex TRF 1 supports telomere length Intensive lipid-lowering therapy at ischemia slows down telomere shortening Telomere length is influenced by age and environmental factors Chromosome instability at ulcerative colitis is related to telomere shortening Impact on telomere length in human cells is a possible road to victory over aging

Stresses and their impact on cell aging Oxidative stress shortens telomere ends and causes aging at molecular level Physical exercises stimulate Nrf2 and NFkB and reduce consequences of oxidative stress at aging Mitochondrial antioxidant SkQ1 has been developed Sulforafan activates Nrf2 factor, by which it induces expression of protein protectors for carcinogens and oxidants Chitosan provides protection from active oxygen forms in neurons by means of factor Nrf2 Colostrinin regulates oxidative stress and prevents aging Insulin inhibits SKN-1 factor and reduces effectiveness of cell protection from active oxygen forms Ras-protein induces aging by changing intracellular level of active oxygen forms Coenzyme Q10 therapy improves mitochondrial function and myocardial contractivity Glutathione demonstrates antioxidant characteristics in retinal pigment epithelium Discovery of three new kinases activating SKN-1 factor Protective gene expression and mitochondrial DNA level increase with decrease of CoQ level Development of methods of genetic therapy for diseases caused by mutations in mitochondrial DNA Acetyl-carnitine and alpha lipoic acid improve mitochondria function Proteasome inhibitors increase cell protection from oxidative stress with the help of factor Nrf2 Mannoheptulose serves as an inhibitor of glycolysis and a mimetic agent of calorie restrictions Calorie restrictions reduce oxidative DNA damage NAD(+) metabolism and calorie restrictions regulate activity of yeast sirtuins First discovered mimetic of calorie restrictions was 2- deoxyglucose AMPK-molecule regulating energy level in cells is activated with decrease in calories consumption Calorie restrictions impact biogenetics of proteasomes in heart Calorie restrictions impact gene expression Calorie restrictions change gene expression quickly and reversibly Short-term resveratrol consumption imitates gene expression of long-term calorie restrictions in mice heart Resveratrol can help in battle against metabolic syndrome

Protein synthesis, modification and degradation in process of aging Battle with «cellular rubish» Aminoguanidin, penicillamine and cysteine prevent protein carbonylation Carnosine inactivates protein carbonyl groups MsrA enzyme impacts number of carbonylated proteins in cells Edavarone inhibits protein carbonylation by direct carbonyl-scavenging mechanism Hydralazin inactivates active carbonylated proteins and protects cells from apoptosis Carbonyl­reductase can protect human neurones from carbonyl stress Caprofene and phenylbutazone can inhibit carbonyl-reductase Adaptogens increase concentration of heat shock proteins Active oxygen forms in physiological amounts can regulate expression and activity of heat shock proteins Gene transfer of heat shock proteins reduces neuronal death in mice with Parkinson disease Heat shock proteins can protect vessels and facilitate tumour destruction process Enhancement of expression of heat shock proteins disables proteasome inhibition Regulations of expression level of proteasome subunits can prevent human skin aging Stimulation of expression of proteasome complex subunits extends cellular lifespans Blockage of proteasome inhibition can reduce proinflammatory molecules synthesis Heat shock proteins can be used for cancer treatment Calorie restrictions induce proteasome signaling pathway with aging Mechanisms of atrophy development depend on muscle fibre type Main forms of proteasome subunits differ in juvenile and old specimens of Drosophila melanogaster EGCG facilitates life extension by stimulation of stress proteins synthesis Study of the role of individual proteins allows understanding of molecular basis of chaperone-dependent autophagy Manipulation of Atg4D-Atg4A complex will allow cells making the right choice between autophagy and apoptosis Injections of LAMP2A receptor allowed «rejuvenating» liver in aged mice Inactivation of autophagy of atg7 and atg12 genes shortens lifespan in nematodes Lentiviral gene therapy slowed down lipofuscin accumulation in retina Discovery of beclin1 protein–main autophagy activator Autophagy activation by Atg8a protein extends lifespan of drosophilae Alzheimer disease is linked with endosomal-lysosomal system disorders Calorie restrictions do not impact lifespan of nematodes at autophagy disorders Riluzole enhances synthesis of heat shock proteins Correction of mechanism of chaperone-dependent autophagy can become a method of treatment of age-dependent diseases UCH-L1 enzyme can influence the mechanism of chaperone-dependent autophagy in various ways Activation of autophagy by TOR protein repressors can protect nervous system from degeneration Blockage of chaperone-dependent autophagy by alpha-synuclein protein leads to Parkinson disease Role of mucolipin­1 protein in chaperone-dependent autophagy has been established Disorders in mechanism of chaperone-dependent autophagy can be the reason of diabetes mellitus Relationship between development of neurodegenerative disorders and dysfunctions in the mechanism of chaperone-dependent autophagy has been identified Vitamin À impacts course of disease in some forms of inherited blindness Method of enzyme replacement therapy has been developed for treatment of diseases affecting central nervous system Discovery of low molecular activator of lisosomal enzymes Early gene therapy caused 3-fold life extension in mice with lisosomal disease affecting nervous system Red wine flavanols prevent accumulation of lipofuscin Role of transglutaminase in development of Alzheimer disease has been determined Replacement and gene therapy is effective in case of neurometabolic diseases Inductors of autophagy are effective for Huntington disease Fructosyl-lysine oxydase and fructose-lysine-3-phosphokinase destroy cross linkages Toxic aggregates of superoxide dismutase are linked to neurodegenerative diseases Methylene blue blocks accumulation of tau protein Role of protein linkages in aging of eye lens and cataract formation has been identified

Programmed cell death (apoptosis) NFkB suppresses apoptosis and prevents osteoporosis development Activation of JNK-kinase in high-fat diet induces apoptosis of liver cells NFêB suppresses apoptosis and helps survival of cancer cells Cytomegaloviruses can block apoptosis in cells

Membrane and intracellular transport Aging can be stopped by reduction of caveolin status Caveolin can become a target for prevention of age-dependent diseases Caveolin restores viability of cells by suppressing synthesis of survivin Medicine for treatment of atherosclerosis can be developed based on caveolin ­1

Regulation at genome and epigenome level C.elegans is an ideal model for studies of mechanisms of aging Retrotransposons inhibit deamination-independent mechanism Different forms of apolipoproteins protect cells from exogenous retroviruses and endogenous retroelements Phase of cell cycle impacts retrotransposition Repair activity of enzymes of aged cells is restored by addition of DNA- glycosylase and DNA-ligase obtained from cells of juvenile specimens DNA repair plays a significant role in controlling processes of aging Activity of mobile genetic elements is suppressed by mechanism of RNA-silencing Modification of conservative evolution genes may lead to life extension Enzymes participating in DNA repair inhibit retrotransposition of mobile elements Discovery of cell factors - inhibitors of retrotransposon DNA mutations accumulate at aging and are tissue-specific Parp1 protein regulates activity of key enzymes of DNA repair Progenitor cells can be a source of mutations in mt DNA Mutations of mt DNA contribute to development of sarcopenia 10-fold life extension was reached for nematodes Changes in some genes of nematodes, drosophilae and mice can significantly extend their life-span 10-fold life extension for yeast became possible Temperature factor plays an important role in transposition of MOS1 element RecQ helicase decreases chromosomal instability Use of biotin in diet positively infliences stability of genome and slows down process of aging Defects in JNK signaling pathway are responsible for changes in gene expression in Ò-cells Arginine methylation regulates telomere length and stability DNA methylation can be responsible for aging and tumour-formation HDAC activity is regulated by phosphorylation Resveratrol-based pharmacological activator of sirtuins slows down appearance of signs of aging Ñhaperones participate in supporting protein homeostasis Studies on structure of sirtuins give insight to possible ways of their activation Vitamin precursors of NAD molecule activate sirtuins Multifunctional CD38 enzyme regulates NAD level and activity of sirtuins Methylation of mobile elements results in their inactivation Inactivation of inhibition of sirtuins by nicotinamide results in their activation Properties of natural activators of sirtuin can be improved by artificial modifications Sir2-deacetylase affecting lifespan is regulated by NAD Sensitivity of cancer cells to action of HDAC inhibitors can become a basis for anticancer treatment Nucleotides with methylation influence on activity of elements have been found in transposons Use of HDAC inhibitors reduces volume of brain injury after stroke Vorinostat inhibits HDAC and suppresses tumor growth in model organisms HDAC inhibitor phenyl-butyrate significantly extends life cycle in Drosophila Decrease in lin-14 protein expression increases lifespan of human cells Histone diacetylase Sir2, p300 and HDAC1 regulate processes of cancer and aging by modulating chromatin Food agents can serve as HDAC inhibitors HDAC inhibitors suppress expression of a number of regulators in cell cycle

Signal cascades Reduction of dTOR function protects against decrease of cardiac function with aging and extends life-span JNK-signaling is responsible for stress-resistance and life-span Role of ÌÀÐÊ signal cascades in cardiovascular pathology has been determined c-Jun kinase hyperexpression increases resistance of cancer cells to apoptosis and aging Deterioration of MAPKs function in many diseases has been identified JNK regulates life-span by modulating nuclear translocation of DAF-16 transcription factor Rapamycin activates autophagy and extends lifespan of mice HSF1 and HSF2 factors form transcriptionally active heterotrimers Celastrol provides protection for cells during stress Radicicol antibiotic provides protection from ischemia by activating HSF1 Accumulation of heat shock proteins protects organism from endotoxins HSF1 factor plays a key role in development of cancer growths in p53 deficient mice HSF1 activity can be regulated by use of SIRT1 diacetylase HSF1 inhibition can become the main effective anticancer strategy Effect of DAF-16 (FOXO) activity on longevity has been proved Effect of cytokines on FOXO activity has been proved New mechanism of ð FOXO regulation has been discovered Ñell apoptosis induction by FOXO factor contributes to longevity of the whole organism I?B-alpha protein blocks NFkB functional activity STAT3 expression determines the fate of embryonic stem cells Development of Alzheimer disease depends on NFkB function ð53 and its signaling pathway are the main target in therapy of cancer and HIV ð53 and NF-kB signal cascades resist neurodegenerative disorders ð53 target gene activation is necessary for control of aging and apoptosis

Possible interference in intracellular processes. Review of technologies. Nanorobots Zinc-finger nucleases can be used for manipulation of mammalian genomes Methods are developed for peptide nucleic acid delivery to human mitochondria Idea of molecular assemblers – devices for “repair” of living organisms– has been proposed Microprobe device for femtolaser microsurgery and obtaining two-photon images has been developed NDI1 gene transfection opens new opportunities for treatment of mitochondrial diseases New methods have been developed for targeted therapy of cancer by use of nanovectors Nanotechnologies can be used for restoration of homeostasis of organism Tissue engineered matrices and constructions for transport of genetic material have been developed Models of medical nanorobots have been developed

Section 4. STUDIES OF EXTRACELLULAR MATRIX AND AGING OF TISSUES

Extracellular matrix and aging Restoration of neprylisin enzyme level prevents development of Alzheimer disease Multifunctional LR11 receptor regulates formation of beta-amiloide Melphalan and transplantation of stem cells cause a remission at AL-amyloidosis Microglial cells induce decrease of accumulated amount of beta-amiloide in brain Inhibitors of binding of SAP protein with amyloid fibrils can be used for treatment of amyloidosis Protein isoforms of cystatin Ñ form amyloid and participate in development of angiopathy Modifications of transthyretin protein can impact amiloide formation Manipulations of nicotinic receptors can reduce levels of beta-amiloide Amount of non-enzymatic biding of skeletal muscles at aging depends on physical activity Pharmacological split of protein binding Accumulation of products of non-enzymatic glycosylation contributes to development of diabetes, sleep apnea and other age-dependent diseases Aminoguanidine inhibits glycation and prevents skin aging Products of non-enzymatic glycosylation impact development of age-related diseases Genetic regulation of receptors of glycation end-products protects from formation of harmful protein complexes Phenacylthiazolin can split cross linkages between proteins Tenilsetam blocks cross linkages between amyloidal plaques B1 and Â6 vitamins can be used to control diabetes complications and signs of aging Rutin (Ð vitamin) and its derivatives decrease protein glycation level Pyridoxine and pyridoxiamine prevent protein glycation and decrease level of lipid peroxidation Ginger, cumin and cinnamon can be used as glycation inhibitors in diabetes and aging Taurin decreases hemoglobin glycation level in erythrocytes Alagebrium breaks cross linkages and improves heart condition at diastolic failure Ways of regulation of lysyl-oxidase – catalyst for formation of intra– and intermolecular linkages have been discovered Process of formation of protein linkages depends on copper content in organism Chelating agents can induce slowing down of aging of eye lens Decrease in number of divalent linkages in collagenic fibers causes osteoporosis Magnesium deficiency activates ÌÌP and results in degradation of extracellular matrix Photodiode therapy decreases ÌÌP level and activates collagen synthesis Decreased COG-2 activity suppresses ÌÌP synthesis and protects atherosclerotic plaques from breakage Estrogene deficiency and tobacco smoke activate ÌÌP and enhance skin aging ÌÌP inhibiting effect results in disturbances of fat tissue development Accumulation of truncated form of lamin À results in hyperactivation of p53 pathway, cell aging and dysfunction of stem cells Overexpression of metalloelastase induces pulmonary emphysema in mice Genistein therapy for prevention of prostate cancer is linked to decrease of MMP-2 level Control of MMP allows controlling process of cartilage tissue destruction Decrease in metalloproteinase activity is directly linked to aging of cells and tissues in general

Immune response. Inflammation and infections. Intracellular relationships Transfection of myoblasts by cFLIP-gene –NF-kappaB inhibitor– activates their differentiation Change over from simple inflammatory reaction to cancer is possible with participation of NFkB Dendritic cells can act as therapeutic agents at autoimmune diseases Aspirin can modulate NFkB signaling pathway of dendritic cells Elimination of senescent neutriphils can be caused by TNF-dependent apoptosis­inducing ligand (TRAIL) Calorie deficiency results in normalization of apoptosis of Ò-lymphocytes in aged mice Foxo3 modulates functions of stem cells and controls increase of immune response of T-cells Condition of aging immune system can be improved by selective elimination of CD28 cells Modulation of NFkB signaling pathway restores antigene activity of virus-affected immune cells Expression of transgenic telomerase restores immune characteristics and proliferative potential of aging Ò-lymphocytes and Ò-cells in patients who are chronically ill with immunodeficiency virus Control of level of insulin-like growth factor­1 supports immune homeostasis Use of genetically modified immune lymphocytes helps in medical treatment of cancer growths Patients suffering from new growth and immunodeficiency conditions have transplantation of Ò-lymphocytes with improved characteristics Cytomegaloviral infection impacts aging of immunity system Diversity of immune classes of Â-lymphocytes decreases with aging Aging of immune system is accompanied by progressive growth of CD8+Ò-cells secreting anti-inflammatory cytokines (IFN-?, TNF-?) Polymorphic variant of interleukin-6 gene is realated to longevity in European populations Ò-cells with increased anticancer activity are developed Proportion of CD8+ and CD4+ Ò-lymphocytes is associated with mortality risk in elderly people Addition of zinc in diet improves thymic productivity Thymic rejuvenation is possible with help of genetically engineered cells secreting IL-7 in situ Calorie restrictions increase cell density in core and thymic medulla Aging impacts differentiation of immune system Ò-cells Calorie restrictions decrease number of old Ò-cells in long-living primates Vaccine for Alzheimer disease decreases level of beta-amiloide protein in monkeys It is not total number but quality of antibodies which changes at aging Copaxone causes induction of Th2 regulatory cells secreting anti-inflammatory and immune-suppressing cytokines Immune sensitivity to reactivation of latent cytomegaloviruses decreases with aging Hematopoietic chimerism is used for creation of anticancer response and transplantational tolerance QCD4–cells can be destroyed by use of antibodies to their markers QNK-cells can serve as regulating agents at inflammation and autoimmune diseases

Oncogenesis and aging Selective inhibition of JNK stops pain and prevents cancer growth Caveolin­1 affects different aspects of tumor progression in different ways «Switching off» caveolin ­3 gene protects from breast cancer Functional activity of ÌÌP decreases with progress of growth development Disturbances of normal function of telomeres and their shortening contribute to genome instability and accelerate cellular aging Telomere shortening significantly decreases proliferative potential of stem cells in elderly people Expression of p16ink4a tumor suppressor in peripheral Ò-lymphocytes can serve as a biomarker of aging Deficiency of ð53tumor suppressor results in rapid decrease of extension of lifespan in mice and significantly increases risk of oncogenesis Expression of telomerase slows down aging in cancer-resistant mice High and carefully controlled activity of poly– ADP-ribosylation cancontributes to life extension Clusterin modulates impact of oxidative stress on cellular aging Anticancer therapy stimulates development of cellular aging in target tumors Discovery of inborn anticancer immune response in mice Chronical impact of stress on cells causes induction of biomarkers of cellular aging

Regeneration of tissues and tissue engineering Insulin impact integrates effects of diet and aging on germinal stem cells maintenance NFêB controls production of many growth factors and is necessary for normal proliferation of stem cells Search for ways of controlling of mechanisms of stem cells division Artificial microenvironment for cultivation of satellite cells has been developed Discovery of new type of stem cells with great potential for regenerative medicine Discovery of biomarkers of stem cells Timeline of behavior of stem cells in organism has been created Decrease of regenerative abilities of tissue with aging can be reversed Activation of MAPK/Notch showed possibility of «rejuvenating» satellite muscle cells Aging of niche impacts proliferative activity of epidermal stem cells Aging of niche impacts proliferation of mesenchymal stem cells Key role of osteoblasts in regulation of hematopoietic stem cells has been proved Decrease in expression level of receptor of growth factor in niche of neurogenic stem cells results in neurogenesis deterioration Trophic effects of stem cells of fat tissue is linked with their secretome and soluble factors Transplantation of monocytes helps to restore tissues after neural or cardiovascular ischemia Therapy of stem cells improves cardiac function and structure of myocard Prenatal therapy of stem cells relieves consequences of heart attack in future Histologically matching stem cells can be used for cell therapy Redox conditions are central modulators of function of progenitor cells Age changes in microglia impact processes of neurodegeneration Four factors are enough for returning cells to pluripotent condition Functionally differentiated macrophages can self-renew in absence of transcription MafB/c-Maf factors Reprogramming of fibroblasts into stem cells became possible, after which cells of cardiac parenchyma were obtained from them iPS-cells are effective in medical treatment of hereditary diseases and can be used in cellular therapy iPS can be obtained based on cells of people of any age including elderly people iPS-cells have some epigenetic differences from true embryonic stem cells iPS-cells can be differentiated to cells of very different tissues Chemical compounds can be used for cell reprogramming iPS- cells can be used for modeling of human diseases It is possible to obtain 100-fold increase of reprogramming effectiveness using keratinocytes 22 types of tissues have been developed using engineering methods Cartilage framework for development of bioengineered trachea has been obtained Autologous chondrocytes for development of bioengineered trachea have been obtained Two-chamber rotation bioreactor for development of bioengineered trachea has been developed First surgery transplantation of bioengineered trachea to human Bioprinting method has been used for reconstruction of scaffold-free blood vessels Cell sheet technology has been used for reconstruction of eye surface and restoration of cardiac tissue New perspectives in evolutionary and phylogenetic issues of regeneration have been discovered Transplantation of organelles of stem cells creates new intestinal mucous coat in dogs Development of biopolymers as materials for transport of medicines to cells Works on engineered modelling of cardiac tissues are conducted Structures of tooth and related bones have been regrown using stem cells MRL-mice are capable of regeneration of damaged tissues Solid bioengineered tubular constructions have been developed using reactorless technique Cryoconservation of whole organs by vitrification method Complex neural networks can be preserved by vitrification Vitrification allows successful freezing of veins, arteries, cartilages, cardiac valves and whole ovaries Functions of organisms after cryoconservation can be restored by use of nanotechnologies Chemical modification of known compounds can become a basis for development of effective cryoprotectors

Section 5. STUDIES OF AGING AT ORGANISM LEVEL

Endocrine system (hormones, biological clock) Regulation imbalance of D vitamin causes premature aging Protective role of cytokines against malignant transformation has been established Decrease of calbindin expression in hypothalamic neurones causes circadian rhythms disorders Melatonin and SIRT1 sirtuins play a role in aging and cancer development Dehydroepiandosterone reduces oxidative stress in mouse brain Insulin/IGF-1 signaling pathway interacting with sirtuins provides survivability of neurons Decrease in activity of growth hormone can lead to life extension Decrease in transmission of insulin/IGF1 signals slows down neurodegenerative processes Decreased insulin level reduces risk of development of age-associated diseases Signaling pathway of insulin controls metabolism and longevity Increase of adipocytokines level in blood plasma can serve as a biomarker of metabolic syndrome in women Decrease in testosterone level can serve as a predictor of development of metabolic syndrome in men Occurrence of metabolic syndrome is linked to decrease of androgen level in men Endocrine correction can slow down process of immunity decrease at aging Controlled hormonal therapy results in slow down of aging

Nervous system Suppression of excessive activity of ÑÀ3 zone of hippocampus at aging results in memory improvement Concentration of calbindin D-28k in neurones changes with aging Intactness of conduction pathways of brain and hereditary polymorphism ADRB2 are predictors of cognitive-preserved aging Development of improvement methods of blood vessels formation in brain structures can prevent development of Parkinson disease Fruit polyphenols impact signal transmission and neurogenesis in aging brain Isoform of adapter protein FE65 is a potential target for treatment of Alzheimer disease Neuroprotective action of Ginkgo biloba extract has been studied For transportation of enzymes and neurotrophic proteins to brain it is necessary to overcome hematoencephalic barrier Vitamin Å can be used in therapy of cholinergic degeneration and memory loss Regulation of activity of p53 protein can have a therapeutic effect on neurodegenerative diseases Studies of role of progesterone in brain aging and development of Alzheimer disease Aging modulates microglial phenotype and its reactivity in development of neurodegenerative processes Accumulation of amiloide can be the reason of microglia degeneration with aging Restoration of myeline in CNS can become a basis for development of therapy of neurodegenerative disorders Astrocytes produce anti-inflammatory and neuroprotective agents Relocation of mobile genetic elements impacts formation of individual characteristics of neurons Development of methods of functional restoration of CNS by targeted control of differentiation of neuron precursors SOX5 controls formation of individual neuron subtypes Cognitive and physical activity induces synaptogenesis in new cells of hippocampus Role of astrocytes in neurogenesis has been established Biodegradable hydrogels stimulate neurogenesis in 3D stem cells culture Stimulation of neurogenesis with antidepressants depends on age Peripheral stimulation improves neurogenesis after ischemia Integrins regulate neurogenesis and increase growth of axons À-activin growth factor is necessary for restoration after neurodegeneration Neurogenesis can be stimulated by therapy with agonists of D2-receptors

External impact on organism and aging Polyunsaturated fatty acids impact age changes of mitochondrial membranes in cardiac muscle 40%-decrease of methionine consumption reduces formation of free radicals in mytochondria and extends life-span Protective components of tea help fighting against processes of brain aging Calorie restrictions decrease risk of metabolic disorders in mammals Calorie restrictions stimulate accumulation of glycogen in skeletal muscles Calorie restrictions significantly decrease risk of atherosclerosis and diabetes Calorie restrictions decrease main factors of risk of coronary heart disease Calorie restrictions extend lifespan as moderate form of stress Calorie restrictions in diet result in decrease of lipid content in liver Positive impact of calorie restrictions is not related to proportion of consumed proteins, fats and carbohydrates Soft stress stimulates synthesis of heat shock proteins hsp and hsf genes participate in adaptive response to stress Number of DNA damages influences the choice between cell survival and apoptosis X-Ray diagnostics can become an anticancer therapy Low concentrations of antibacterial drugs cause hormetic effect in E.coli

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Leading researchers of mechanisms of aging and life-extension methods


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