20 20 25 25 30 30 35 35 40 40 45 45 50 50 55 55 60 60 65 65 70 70 80 80 AgeAge Increase in probability of infections Heart failure Fibrosis Deterioration of nutrition of cells Accumulation of glycated proteins Hypothalamus hypotrophy Accumulation of lipid-protein crosslinks Nonhomologous recombination Decline in impact of sympathetic nervous system on the heart Deterioration of toxins removal Decline in cell functions Decline in the process of synthesis of collagen and elastin Atrophy of the lung alveoli Chronic generalized lingering inflammation Accumulation of amyloid fibrils (amyloid beta) Immunodeficiency Coronary Atherosclerosis Decline in the number of asinus (alveolar) X-syndrome Age-related changes in the liver Oncogenesis (malignant and benign tumors) Hypotrophy of adrenal glands Loss of the elasticity of lung tissue Tissue hypotrophy Pneumonia Incomplete digestion of food Changes of the physical and chemical properties of the membrane matrix Decline in protein synthesis Hypoxia Accumulation of denatured proteins Breast Cancer Spleen atrophy Decline in physical performance Accumulation of protein aggregates Decline in activity of the functional elements of fabrics Type II diabetes Proliferation of smooth muscle cells (inflammation) Loss of mobility Point mutations Decline in number of B-lymphocytes that are responsible for specific reactions Inhibition of the proteasome Pressure ulcers and atrophy Increase in the production of FSH (Follicle Stimulating Hormone) and LH (luteinizing hormone) Heart insufficiency Reducing the speed of reflexes Reduction of number of T-helper cells Cardiac insufficiency Castle factor no longer converts B12 vitamine Increase in activity of parathyroid hormone Damage to T-cells Increase in secretion of prolactin Dysregulation of various systems of the organism Obesity Myocardial infarction Renal insufficiency Decline in the number of circulating immune complexes Bony spikes Production of inflammatory cytokines Alveoli are connected to each other Decline in functional activity (of tissues, organs, systems) Senile infirmity The accumulation of nonfunctional proteins Sarcopenia Decrease in secretion of thyroid hormones Reduced serotonin Reduction of insulin production DNA damage Formation of malonic aldehyde Hypotrophy of the endocrine part Reducing the number of functional cells Damage of the mitochondrial membranes Multiple sclerosis Increase in the number of collagen fibers (between cells) Ca leaching from the bones Prostate cancer Decline in secretion of IGF-1 (Insulin-like growth factor-1) Growth of amyloid plaques Some SFC Weakening of the stem cells pool due to homing disruptions Decline in the rate of cell division Chromosomal aberrations Accumulation of lipofuscin Formation of foam cells Lung cancer Alzheimer disease Decline in estrogen production Anemia Decline of the potassium level Crosslinks Osteochondrosis Hypertension Deterioration of myocytes Decrease of cell proliferation ??? The accumulation of nonfunctional proteins Accumulation of damage in myocytes Blocking proliferation signals Excess activation of proto-oncogenes Emergence of unsuppressed cancer cell foci by immune system Genetically determined factors Hypoplasia of the tissues Degradation of the extracellular matrix in cartilage Degradation of the extracellular matrix in the skin Renal insufficiency Changes in the receptor sensitivity of cell Genomic instability Decline in norepinephrine secretion Growth factor blocking Formation of signal of double-stranded break of the DNA Damage to the endothelium Decline in the number of myocytes Decline in the production of TSH (thyroid-stimulating hormone) Loss of telomere covering proteins (TRF2) Rheumatism Various mtDNA damage Uremia Bad homing Telomere shortening Abnormal chromatin Replicative aging (permanent cessation of mitosis) Deterioration of the microcirculation in the pancreas Decline in c-complement synthesis Loss of the regenerative potential of satellite cells Changes in the permeability of the alveolar wall Inflammatory reactions in the tissues Decreased vital capacity of lungs The immune system can not extinguish all inflammations Deceleration of regeneration Stroke Hypotrophy of epiphysis Increase of probability of fractures Compaction of membrane Increase in the secretion of vasopressin Infringement of functions of cells Decrease in the secretion of dehydroepiandrosterone Compression of the organ Accumulation of defective collagen Deterioration of work of ensemble of cells Damage to the nuclear lamina Hypoxia (of varying degrees) Hypotrophy of thyroid Development of ROS, free radicals and other active molecules Emergence of defective mitochondria Epigenetic disturbances (cross-linking of DNA-protein, DNA demethylation) Accumulation of misfolded proteins Arthritis Transposition of mobile genetic elements 8-oxo-2'deoksiguanozin in the promoter and enhancer DNA regions Osteoporosis Hypotrophy of gonads Deterioration of of cognitive abilities of brain Reduction of the number of intercellular connections Prostatic hypertrophy Chemical mutagens Adverse change in the extracellular matrix Deterioration of tissue nutrition Mitotic catastrophe Increase in parathyroid hormone secretion DNA-DNA crosslinks Cell volume reduction Adverse change in the constitutive expression of genes Parkinson's Disease Decline in the number (and quality) of adhesion receptors Decline in the number and quality of the ribosomes Formation of atherosclerotic plaques Miscoordination of the nervous system processes Decreased secretion of sex hormones (testosterone, estradiol, progesterone) Disruption of metabolite transport across membrane Smoking Decline in production of ACTH (Adrenocorticotropic hormone) Respiratory insufficiency Reduced elasticity of blood vessels CHD Skin aging Impairment of the inducible gene expression Immune system cells do not have time to eliminate the violation Pulmonary insufficiency Abnormal daily rhythm of secretion of neuropeptide Y Integration of retroviruses in DNA Increase in the number of aldehydes Decline inf the assimilation of calcium and vitamin D in the intestine Accumulation of oxidized proteins Decline in the activity of the enzyme system Decline in secretion of thyroid hormones Reduced synthesis of calcitriol Hard UV radiation Nonperforming protein components of antioxidant systems (FAS does not work properly) The death of the organism Decreased secretion of melatonin Blocking of the replication forks Mutations in mtDNA The accumulation of fatty acids in the blood Decline in the number of neurons Strengthening of the autoimmune response Formation of alkylated bases Reduced nutrition of cells Reducing the number of capillaries Various pathologies (intestinal intoxication) Increased activity of AMC Reduction of number of entities of T-lymphocytes (hypoplasia) Senile changes in tissues Degradation of the extracellular matrix in tendons Menopause and Andropause Suppression of autophagy Overfilling in lysosomes Suprathreshold temperature Lack of insulin High glucose tolerance Reduced ATP production (in some cells) Hypotrophy of tissue Adiposis Increased lprobability of falling Lipid peroxidation in membranes Reduced synthesis of ribosomal RNA Increase in intercellular distance Accumulation of carbonylation protein Increase in peripheric vascular resistance Decrease in the conductivity of nerve fibers Decrease in bone mass Myocardiopathy Reduced synthesis of mRNA Increased levels of Ca in the blood Appearance of defective cells Reduced generation of Q10 Ionizing radiation Permanent overeating Hypoplasia of muscle tissue Accumulation of cellular debris Hypotrophy of the muscles of the chest Loss of division of epithelial cells Insufficient turnover Hypotrophy of the endocrine part of pancreas Some decrease in the functionality of cells Atrophy of the reticular cells of the thymus Hypoplasia of the tissues Change of selective conduction of metabolites Reduction of adaptive response Loss of elasticity of the walls of pulmonary alveoli Decline in secretion of various neurotransmitters Raise of basic level of glucose Hypotrophy of neuroendocrinal nodes Decreased expression of components of repair systems Growth of putrefactive flora Reducing the number of active copies of DNA encoding ribosomal RNA and proteins Deterioration of the signal transmission Decline in the amount of information molecules Accumulation of extracellular debris Decreased secretion of growth hormone (GH) Increase in ROS Permanent illumination In glands in muscles in osteoblasts in fibroblasts (matrix) in the immune system Damage to mitochondrial enzymes Parietal cells are attacked by the immune system Presentation of wrong antigens Reduction of motor activity NUMT - pseudogenes Lung emphysema p53-dependent irreversible mitotic delay Deterioration of of blood circulation Decreased activity of heat shock proteins Deterioration of the microcirculation in biological fluids Decline in assimilation of vitamins BDCE Change in hormone and other signaling factors receptors sensitivity Sticking with amyloid Accumulation of protein crosslinks Chronic infections Hypotrophy of organ Changes in the structure of apolipoprotein (LDL) Hypotrophy of bone marrow Abnormal cell metabolism Immune system perceives these cells as alien Decrease in the number of intracellular components (mitochondria, ribosomes) Hypotrophy of the anterior pituitary Telomere shortening, loss of T-loops Breaks of DNA strands Penetration of lipid oxides and fibrin and platelets in the subendothelial space Decrease in membrane permeability Growing proportion of the connective tissue in the cartilaginous basis of the trachea, bronchus and lung Depression Increase in secretion of glucocorticoids Abnormal gas exchange of CO2 and O2 Change of the threshold of sensitivity in the center of appetite of the hypothalamus Destruction of the sympathetic endings Age-switching activity of different subunits of proteasomes The oxidation of elastin Reduction of the permeability of the intercellular space Micronutrient deficiency Abnormal of cerebral circulation Production of metalloproteinases Increase in the production of gonadotropin Overfilling of macrophages by lipid oxides Autoimmune diseases Age-related hypovitaminosis Temporary adaptive cessation of mitosis Increase in fraction of the proteasome subunits with reduced activity Change of level of arterial pressure Legend– immune system– nervous system– hormones– metabolic system– connective tissue– cardiovascular system– respiratory system– cancer– intersystem linksAuthors– Medvedev D.A.Research Center for Advanced Technologies– Artyhov I.V.Institute for the Biology of Aging– Kaurov B.A.Russian State Scientific and Clinical Center– Krementsova A.V.Institute of Biochemical Physics– Moskalev A.A.Komi Institute of Biology– Mamaev V.B.Institute of Biochemical Physics– Pasyukova E.G.Institute for Molecular Genetics– Sarvilina I.V.Novomedicina– Valeriya PrideResearch Center for Advanced Technologies– Ejov M.D.Research Center for Advanced Technologies– Ilyin P.A.Research Center for Advanced Technologies– Zimin E.A.Research Center for Advanced Technologies– Lokk A.N.Research Center for Advanced Technologies Version 62.0 2008-2014 Research center for Advanced Technologies. http://sciencevsaging.org Author of the idea: Medvedev D.A.