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ADAPTATION TO THE CHANGES IN ENERGY METABOLISM THROUGH AGING AS A STRATEGY OF LONGEVITY H.V.TERESHINA T.M. YURINA Russian Research Institute of Gerontology, Moscow Environment E HYPOTALAMUS RELEASING FACTORS EPIPHYSIS PITUITARY AMINES E HORMONES E Internal medium E E Levels of energy utilization BASAL LEVEL • Growth • Self maintenance • Physical and mental activity • Reproduction • Thermogenesis inside EXTREME LEVEL (STRESS) Danger Cold Starvation max Immobilization Heat Overnutrition min outside TYPES OF HOMEOSTASIS V.M. Dilman ADAPTATIVE REPRODUCTIVE ENERGETIC CATECHOLAMINES ADRENALINE GLUCAGON CORTISOL SEX HORMONES GROWTH HORMONE LEPTIN INSULIN SUBSTRATE PREFERENCE CATECHOLAMINES CORTISOL GLUCAGON ADRENALINE SEX HORMONES GROWTH HORMONE LEPTIN INSULIN GLUCOSE (GLU) CHOLESTEROL (CHOL) FATTY ACIDS (FA) GLU FA CHOL CHOL INTESTINE STEROIDOGENIC TISSUE BRAIN GLU CHOL GLU FFA CHOL LIVER GLU GL FA FFA CHOL FFA GLU+FA=TG ADIPOSE TISSUE MUSCLE GLU FA liver hyper hypo glycemic state Glucose glycemic In blood state (insulin) (glucagon) IR cell pancreas INTESTINE bile ABC FA chol SRB1 HDL SRB1 LIVER STEROIDO GENIC TISSUE Bile acids LDL LDLr CD36 estradiol macrophage ABC estradiol testosterone TG BILE INTESTINE TG-rich LP remnants LIVER TG TG FFA FA LEPTIN GH FFA MUSCLE HEART LR GLU+FA=TG ADIPOSE TISSUE Fatty acids: main functions Fuel Fat deposition (palmitic acid, oleic acid) Membrane structure Phospholipid composition Cholesterol content Raft’s composition Fluidity Receptors’ activity Transmembrane messengers Hypothalamus Neuronic cells Peripheral cells Cholesterol transport and distribution (oleic acid) Immune system Linoleic and arachidonic acid metabolites Regulation of gene transcription (PUFA) Fatty acids’ role in the onthogenesis • Proliferation of somatic cells (growth and development) • Boundaries of the reproductive period • Energy accumulation (adaptation) CHAHGES IN THE FAT AND WATER CONTENT IN THE HUMAN FOETUS TISSUES DURING INTRAWOMB DEVELOPMENT: 2 - WATER 3 – FAT M - BODY MASS WEIGT/VOLUME Changes of the free fatty acid content in the blood of girls and boys (young adults) through the 0-25 yr period of life Weight/Height Changes of the free fatty acid content in blood in onthogenesis Leptin resistance Insulin resistance ♂ I period 0-25 yr ♀ II period 25-50 yr III period Weight 50-100 yr Weight+Height Adipose tissue Nonadipose tissue Fatty acid utilization in onthogenesis I period Proliferation (growth and development) II period Reproduction Deposition in the adipose tissue III period Deposition in nonadipose tissues Hypotalamic sensitivity (V.M. Dilman) I period (0-25 yr) Growth hormone (+ +) Sex hormones (- +) Leptin (+) II period (25-50 yr) Growth hormone (+ -) Sex hormones (+ +) Leptin (-) III period (50-100 yr) Growth hormone (- -) Sex hormones (- -) Leptin (-) Leptin resistance results in increased fat body mass which leads to the loss of the reproductive homeostasis This is accompanied by certain disturbances in the cholesterol distribution and utilization Cholesterol level in blood arises Deposition of fatty acids in adipose tissue reaches its maximum to the end of the reproductive period Adaptative homeostasis (to the environment) decreases Increased levels of free fatty acids, glucose and cholesterol develop an internal stress Means of adaptation to the internal stress Deposition of fatty acids in nonadipose tissues Oxidative stress (fatty acids) Cholesterol deposition Proliferation (IGF-I glucose) Deseases and death Apoptosis (palmitic acid, glucose) cell loss Energy expenditure decreases Maintenance of the energy homeostasis in the III period as a strategy of longevity Calorie restriction Apoptosis (loss of the cell mass) Physical and mental activity Mild stress Energy flux Complete energy expenditure Adaptation is an ability of a system to keep itself by giving an adequate answer not only to challengers of the environment but to the changes of it’s own inner conditions. Adaptation is an expression of lust for survival and existence as long as possible