WHAT MAKES US AGE?WHAT MAKES US AGE?

Life Cycle IILife Cycle II

JOHN TURNERJOHN TURNER

AGE 67AGE 67 AGE 77AGE 77

AGE 90AGE 90AGE 80AGE 80

ELEANOR HYNDMAN

WHY DO WE AGE?

• IS IT GENETICS?

• ENVIRONMENTAL DAMAGE?

THE BIG QUESTION

DEVELOPMENTAL—

GENETIC THEORIES• Genetic makeup

determines factors directly affecting aging

• Programmed & directed in the body

• Aging is Predetermined

ENVIRONMENTAL—

NON- GENETIC THEORIES• Due to random events that

occur over time• Aging caused by

environmental damage• Controlled extrinsically

Theories of Aging

• Finite Lifespan

• Immune System Failure

• Hormonal

• Energy/Caloric Restriction

• Error Theory

• Redundant DNA

• Transcription

• Cross-Linking

Finite Limit Theory

• Hayflick & Moorehead (1961)• Landmark Study--Cells Have Time-clock• Cells Have Limited Life Span

– Apoptosis=Programmed cell death• Cells Proliferated and Divided• Alterations & Degeneration• Cessation of Growth & Division

Neuroendocrine & Hormonal Theory

• Denckla (1974) Endocrinologist Gerontologist

• Aging Mediated in Brain• Functional Decrements in

neurons and associated hormones dictates aging rates

Immunological Theory

• Walford (1969, 1979)• Reduced T-cell function with age

– Decline in Immune System Function• Immune System unable to distinguish between self &

non-self– Age associated increase in autoimmune disorders– Lupus, Scleroderma

Free Radical Theory

• Accumulates Over Time from Oxygen Metabolism– Charged Ion with unpaired

electron– Damages membrane

proteins, mitochondria, etc.– Decreased cellular integrity

• Free radicals associated with atherosclerosis, cancer

Metabolism, Free Radicals, & Life Span

• Metabolic Rate Directly Related to Free Radical Production

• Inverse Relationship Between Metabolic Rate & Life Span

• Hypothesis--Lower metabolic rate, lower free radical production, increase life span

Caloric Restriction Theory

• Walford (1987)--”Dr In Vivo”

• Restriction of Caloric Intake

• High quality nutrient/low calorie diet increases longevity– Supplements with vitamins/minerals/moderate

exercise

• Gradually lose weight until maximal metabolic efficiency, retards aging

Error Theory

• Orgel (1963)• “Any accident or error in either the

machinery or the process of making proteins would cascade into multiple effects”

• DNA--RNA--protein synthesis• Accumulation of errors over time• “Error Crisis” result in impaired cell

function

Redundant DNA

• Medvedev (1972)

• Combination of Finite Limit & Error

• Ability to repair errors to genetic material decreases with age

• Errors in Cellular DNA

• Reserve DNA (error free) utilized

• Cell death when reserve DNA gone

Cross-Linking Theory

• Bjorksten (1942)• Proposed Chemical

reaction of Cross Linking of Macromolecules related to aging– Occurred during sun

tanning--lose elasticity– Loss of Tissue Elasticity

“Number of hypotheses is generally inversely proportional to the clarity of the problem.”

--Frolkis

WHY SO MANY THEORIES?

• Biologic Gerontology New Field

• Can One Single Theory Explain All Aging Processes?

IS THERE A RIGHT ANSWER?