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Treviso Geriatric Oncology Advanced Course

BIOLOGY OF AGE

“Every man desires to live long, but no man wishes to be old””””

Jonathan Swift 1727

Longevity model Monochorionic Twins

Sci Aging Knowledge Environ 2001; 2001

HAYFLICK: The Cellular Theory Of Aging

The author demontrates that primary human cell strains each have a characteristic replicative lifespan or "doubling potential", and that this lifespan was an intrinsic characteristic that can differ between strains.

He identified the number of divisions rather than the amount of elapsed time in culture as the critical parameter of lifespan.

Nat Rev Genet 2002; 3: 165-75

DROSOPHILA MELANOGASTER

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Nat Rev Genet 2002; 3: 165-75

CAENORHABDITIS ELEGANS DAF 2 CAENORHABDITIS ELEGANS

Clin Invest 2004; 113: 8-13

TELOMERES AND TELOMERASE

Pro-inflammatory

agents

Neuroendocrine

Dysregulation

Inflammation

caused by

environmental

and dietary

exposure

Chronic

inflammation

Infection

Autoimmunity

Oxidative Stress

Mitochondrial Deletion

Shortened Telomeres

DNA Damage

IGF-1

Dehydroepiandrosteron

e- sulfate

Sex steroids

Interleukin 6

Oxidative StressCoagulation factors

TNF-α

IL 6

Cell Senescence

Glucose Metabolism

Inflammaging

Coagulation factors

TNF-α, IL 6

Oxidative Stress

Glucose Metabolism

AGING

TYPES OF INFLAMMATION

Therapy-induced

inflammation

Tumor-associated

inflammation

Inflammation

caused by

environmental

and dietary

exposure

Chronic

inflammation

Infection

Autoimmunity

Mutations

Genomic instability

Tumor promotion

Angiogenesis

Mutations

Genomic instability

Tumor promotion

Angiogenesis

Tumor growth/survival

Genomic instability

Angiogenesis

Immunosuppression

Metastasis

Cancer cell killing

Tumor re-emergence

Resistance to therapy

Antigen presentation

Cancer cell killing

Tumor

development

TYPES OF INFLAMMATION

Grivennikov SI, Cell. 2010 Mar 19;140(6):883-99.

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Senescence: does it all happen at the ends?

Nature

Eat Less Live MoreCan calorie restriction extend human lifespan?

A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan

Trends Neurosci 2001; 24: S21-31

Molecular mechanisms of brain aging and neurodegenerative disorders: lessons from dietary restriction

A-B: 27.5 yrs

normal diet

C-D: 27.5 yrs

caloric

restriction

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The Blue Zones

LONGEVITY IS WHAT WE EAT AND...?

BLUE ZONES

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Okinawa

• World’s longest disability-free life expectancy

• Live seven years longer than Americans

• Five times as many centenarians

• One-fifth breast and colon cancer

• One-sixth the rate of heart disease

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757881848790

WomenMen

80

76

89

87

ADVENTISTS

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• Downshift

Move Naturally

Right Outlook

Eat Wisely

• Wine @ 5

Connect

• Purpose Now

The Power 9Secrets to Living Life Longer, Better• Plant Slant

• 80% Rule

• Loved Ones First

• Belong

• Right Tribe

World’s Blue Zones Diets…

OkinawaSardinia ikaria nicoya adventists

{plant-based foods account for vast percentage of diet}

Average Longevity diet…

Sugars

Animals

Plants

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of all U.S. medical costs are explained by physical inactivity, food choices and portion size,

tobacco and unmanaged stress.

84%