at a very old age Nir Barzilai M.D. The Ingeborg and Ira Leon - - PowerPoint PPT Presentation

Nir Barzilai M.D.

The Ingeborg and Ira Leon Rennert Chair of Aging Research Professor of Medicine and Genetics Director: Institute for Aging Research PI: Nathan Shock Center of Excellence Albert Einstein College of Medicine

How to die young at a very old age

Aging: Environment or genes?

Longevity in the Torah

• Methuselah
• Noah
• Abraham
• Isaac
• Jacob
• Joseph
• Moses

969 years 950 years 175 years 180 years 140 years 110 years 120 years

Aging is the major risk factor for death

from ALL chronic diseases

Do we, humans, age at different rates?

What is the evidence for success in the goal of delaying aging?

AGING CELLS AGING GENOME AGING METABOLISM

Longevity

• Healthy life-span has been extended in

numerous models.

• Relevant drugs have been used in

humans.

Genetics of human longevity

Can a study design depict the challenges of genetics of aging?

• Only ~1/10,000 individuals is 100 years old

(n~600; 95-112)

• There is a remarkable family history of exceptional

longevity in parents, siblings and offspring of “centenarians”

• Hypothesis:

1) Perfect genome

92

5,000 10,000 15,000 20,000 25,000 60-70 Yo >100 Yo 24,000 8,000

Medical cost ($) during the last 2 years of life

Centenarians interaction with the environment

(n=477, 75% females)

• Over weight/obese:

48% 44%

• Smoking:

60% 30%

• Alcohol (daily):

24% 12%

• Physical activity:

43% 47% (Moderate: regular walking, bicycling, housework)

• Vegetarians: 2.6%

Centenarians Men Women

Swapnil Rajpathak and Jill Crandall

‘Environmental’ risk

J Am Geriatr Soc. 2011 Aug 3

Genetics of human longevity

Can a study design depict the challenges of genetics of aging?

• Only ~1/10,000 individuals is 100 years old

(n~600; 95-112)

• There is a remarkable family history of exceptional

longevity in parents, siblings and offspring of “centenarians”

• Hypothesis:

1) Perfect genome/environment 2) Protective genes to assure human’s longevity

A major barrier to conducting a study of centenarians

Is there an appropriate control group?

• The cohort assembled to date (“LonGenity”) is

unique:

• Offspring of centenarians are enriched with

longevity phenotypes and genotypes

• Study of offspring permits comparisons with age-

and gender-matched controls.

• All Ashkenazi Jews

5 10 15 20 25 30 35 40

DM (%) MI (%) Stroke (%) Prevalence in population HTN (%)

Offspring are less likely to have age- related diseases than controls

JAGS 2004; 52:274

P O C

** ** ** **

Proband Offspring Control ** p<0.01

Diminished GH/IGF-1 action improves longevity across nature

Ghr-/-, lit/lit, GHA, Wt, bGH

Ponies live longer than thoroughbreds Small dogs live longer than large dogs IGF-1R+/-females, but not males, live longer Longer lifespan in daf-2 mutants

Longevity

Dementia-Free survival Alzheimer’s-free survival

CETP V genotype and cognitive function: High HDL cholesterol

Sanders et al JAMA. 2010 Jan 13;303(2):150-8.

Age in years Dementia-free Survival 75 80 85 90 95 100 0.0 0.2 0.4 0.6 0.8 1.0 Isoleucine homozygotes Valine heterozygotes Valine homozygotes Age in years Alzheimer's disease free Survival 75 80 85 90 95 100 0.0 0.2 0.4 0.6 0.8 1.0 Isoleucine homozygotes Valine heterozygotes Valine homozygotes

How does the environment effects the genome?

Longevity in the Torah

• Methuselah
• Noah
• Abraham
• Isaac
• Jacob
• Joseph
• Moses

969 years 950 years 175 years 180 years 140 years 110 years 120 years

Stress Caloric restricton

Exceptional Longevity is Associated with Decreased Reproduction

People with exceptional longevity Controls Number of Children

1) If you prevent aging you may prevent its diseases 2) Research to the biology and genetics of aging is bearing fruits (or medications…) 3) Healthy aging is not going to destroy us ($) Your genetic make up is modifiable: Food, drug development, prayers etc…

Nir Barzilai M.D.

The Ingeborg and Ira Leon Rennert Chair of Aging Research Professor of Medicine and Genetics Director: Institute for Aging Research PI: Nathan Shock Center of Excellence Albert Einstein College of Medicine

How to die young at a very old age

Funding for this series is provided in part by:

 Program for Jewish Genetic Health UJA-Federation of New York A generous grant in honor of Beatrice Milberg