1. 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

2. HYPOTALAMUS PITUITARY EPIPHYSIS Environ- ment AMINES RELEASING FACTORS Internal medium HORMONES E E E E E

3. Levels of energy utilization BASAL LEVEL Growth Self maintenance Physical and mental activity Reproduction Thermogenesis EXTREME LEVEL (STRESS) Danger Cold Starvation Immobilization Heat Overnutrition inside outside max min

4. TYPES OF HOMEOSTASIS ADAPTATIVE REPRODUCTIVE ENERGETIC CATECHOLAMINES ADRENALINE GLUCAGON CORTISOL SEX HORMONES GROWTH HORMONE LEPTIN INSULIN V.M. Dilman

5. SUBSTRATE PREFERENCE GLUCOSE (GLU) CHOLESTEROL (CHOL) FATTY ACIDS (FA) CATECHOLAMINES CORTISOL GLUCAGON ADRENALINE SEX HORMONES GROWTH HORMONE LEPTIN INSULIN

6. GLU FA CHOL LIVER STEROIDOGENIC TISSUE CHOL INTESTINE BRAIN MUSCLE ADIPOSE TISSUE GLU FFA CHOL GLU FA GLU GL FFA GLU FA CHOL GLU+FA=TG

7. Glucose In blood hyper glycemic state (insulin) hypo glycemic state (glucagon) pancreas liver cell IR

8. LIVER STEROIDO GENIC TISSUE INTESTINE macrophage ABC LDLr SRB1 HDL ABC LDL estradiol testosterone chol Bile acids CD36 bile FA

9. TG LIVER INTESTINE MUSCLE HEART ADIPOSE TISSUE FA FFA TG BILE GLU+FA=TG TG FFA GH LEPTIN LR TG-rich LP remnants

10. 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 Cholesterol transport and distribution (oleic acid) Immune system Linoleic and arachidonic acid metabolites Regulation of gene transcription (PUFA) Hypothalamus Neuronic cells Peripheral cells

11. Fatty acids’ role in the onthogenesis Proliferation of somatic cells (growth and development) Boundaries of the reproductive period Energy accumulation (adaptation)

12. CHAHGES IN THE FAT AND WATER CONTENT IN THE HUMAN FOETUS TISSUES DURING INTRAWOMB DEVELOPMENT: 2 - WATER 3 – FAT M - BODY MASS WEIGT/VOLUME

13. 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

14. 0-25 yr25-50 yr50-100 yr Changes of the free fatty acid content in blood in onthogenesis Weight+Height Weight Leptin resistance Insulin resistance ♀♂ Adipose tissueNonadipose tissue I period II periodIII period

15. 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

16. Hypotalamic sensitivity  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 ( - ) (V.M. Dilman)

17. 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

18. Deposition of fatty acids in adipose tissue reaches its maximum to the end of the reproductive period Adaptative homeostasis (to the environment) decreases

19. Increased levels of free fatty acids, glucose and cholesterol develop an internal stress

20. Means of adaptation to the internal stress Deposition of fatty acids in nonadipose tissues Oxidative stress (fatty acids) Cholesterol deposition Proliferation (IGF-I  glucose) Apoptosis (palmitic acid, glucose)  cell loss Energy expenditure decreases Deseases and death

21. 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

22. 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