ADAPTATION TO THE CHANGES IN ENERGY METABOLISM THROUGH

AGING AS A STRATEGY OF LONGEVITY

H.V.TERESHINAT.M. YURINA

Russian Research Institute of Gerontology, Moscow

HYPOTALAMUS

PITUITARY EPIPHYSIS

Environ- ment

AMINES

RELEASING FACTORS

Internal medium

HORMONES

E

E

E

E

E

Levels of energy utilization

BASAL LEVEL• Growth• Self maintenance• Physical and mental activity• Reproduction• Thermogenesis

EXTREME LEVEL (STRESS)

Danger Cold

Starvation

Immobilization HeatOvernutrition

inside

outside

max

min

TYPES OF HOMEOSTASIS

ADAPTATIVE

REPRODUCTIVE

ENERGETIC

CATECHOLAMINES

ADRENALINE

GLUCAGON

CORTISOL

SEX HORMONES

GROWTH HORMONE

LEPTIN

INSULIN

V.M. Dilman

SUBSTRATE PREFERENCE

GLUCOSE (GLU)

CHOLESTEROL (CHOL)

FATTY ACIDS (FA)

CATECHOLAMINES

CORTISOL

GLUCAGON

ADRENALINE

SEX HORMONES

GROWTH HORMONE

LEPTIN

INSULIN

GLU FA CHOL

LIVER

STEROIDOGENIC TISSUE

CHOL

INTESTINE

BRAIN

MUSCLE

ADIPOSE TISSUE

GLU

FFA

CHOL

GLU FA

GLU

GL

FFAFFA

GLU

FA

CHOL

CHOL

GLU+FA=TG

Glucose

In blood

hyper

glycemic

state

(insulin)

hypo

glycemic

state

(glucagon)

pancreas

liver

cell

IR

LIVER STEROIDO

GENIC

TISSUE

INTESTINE

macrophage

ABC

LDLr

SRB1SRB1

HDL

ABC

LDL

estradiolestradiol

testosterone

chol

Bileacids

CD36

bile FA

TG

LIVER

INTESTINE

MUSCLEHEART

ADIPOSE TISSUE

FA

FFA

TG

BILE

GLU+FA=TG

TG

FFA

GH

LEPTIN

LR

TG-rich LP remnants

Fatty acids: main functions

Fuel Fat deposition (palmitic acid, oleic acid)

Membrane structurePhospholipid compositionCholesterol contentRaft’s compositionFluidityReceptors’ activity Transmembrane messengers

Cholesterol transport and distribution (oleic acid)Immune systemLinoleic and arachidonic acid metabolites

Regulation of gene transcription (PUFA)

Hypothalamus

Neuronic cells

Peripheral cells

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

0-25 yr 25-50 yr 50-100 yr

Changes of the free fatty acid content in blood in onthogenesis

Weight+HeightWeight

Leptinresistance

Insulinresistance

♀♂

Adipose tissue Nonadipose tissue

I period II period III period

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

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)

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 tissuesOxidative stress (fatty acids)Cholesterol depositionProliferation (IGF-I glucose)

Apoptosis (palmitic acid, glucose) cell loss

Energy expendituredecreases

Deseases and death

Maintenance of the energy homeostasis in the III period as a strategy of

longevity

Calorie restrictionApoptosis (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