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 р38 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
Carbonyl-reductase 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 mucolipin-1 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 А 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
NFкB 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 Т¬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
Сhaperones 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 lifespan
JNK-signaling is responsible for stress-resistance and life-span
Role of МАРК 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 р FOXO regulation has been discovered
Сell apoptosis induction by FOXO factor contributes to longevity of the whole organism
IκB¬alpha protein blocks NFkB functional activity
STAT3 expression determines the fate of embryonic stem cells
Development of Alzheimer disease depends on NFkB function
р53 and its signaling pathway are the main target in therapy of cancer and HIV
р53 and NF-kB signal cascades resist neurodegenerative disorders
р53 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 С 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 В6 vitamins can be used to control diabetes complications and signs of aging
Rutin (Р 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 ММP and results in degradation of extracellular matrix
Photodiode therapy decreases ММP level and activates collagen synthesis
Decreased COG-2 activity suppresses ММP synthesis and protects atherosclerotic plaques from
breakage
Estrogene deficiency and tobacco smoke activate ММP and enhance skin aging
ММP inhibiting effect results in disturbances of fat tissue development
Accumulation of truncated form of lamin А 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 apoptosis-inducing ligand (TRAIL)
Calorie deficiency results in normalization of apoptosis of Т-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
Т-lymphocytes and Т-cells in patients who are chronically ill with immunodeficiency virus
Control of level of insulin-like growth factor-1 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 Тlymphocytes with improved characteristics
Cytomegaloviral infection impacts aging of immunity system
Diversity of immune classes of В¬lymphocytes decreases with aging
Aging of immune system is accompanied by progressive growth of CD8+Т¬cells secreting antiinflammatory cytokines (IFN¬γ, TNF¬α)
Polymorphic variant of interleukin¬6 gene is realated to longevity in European populations
Т-cells with increased anticancer activity are developed
Proportion of CD8+ and CD4+ Т-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 Т-cells
Calorie restrictions decrease number of old Т-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
Caveolin-1 affects different aspects of tumor progression in different ways
«Switching off» caveolin -3 gene protects from breast cancer
Functional activity of ММP 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 Т-lymphocytes can serve as a biomarker of aging
Deficiency of р53tumor 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
NFкB 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 СА3 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 Е 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
А-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
DATABASE
Leading researchers of mechanisms of aging and life-extension methods