Almaty 03|12| 2012

The Buck Institute for Research on Aging

Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy

• Best-in-class R&D institution that is solely focused on Aging and Chronic Diseases• Mission: to increase the healthy years of life through aging research and education on

the aging process

• Unique Assets: 20 Head Investigators, 140 PhDs, >100 supporting staff• Focusing on biogerentology, Aging & aging disorders, Genetics, Epigenetics, Animal

models of aging• Age-related disease: Neurodegenerative disease, Cancer, Cardiovascular disease,

Metabolic disease

The Buck Institute

CDs: Heart, Stroke, Hypertension, Lung, Mental, Diabetes & Cancer

December 13th, 2003

The shape of things that are here! December, 2011

Prevention and Treatment- Current Options

Metabolism

Damage

Pathology

Prevention

Treatment

Intervention

Treatment

Morbid Complications

‘Primordial’

Primary

Secondary Prevention

Tertiary Prevention

Death

Smoking, Body Weight, exercise

Statins, aspirin + primary prevention

Control cholesterol, hypertension, glycemia, etc.

Risk Factor

The Buck Institute

Compression & Expansion of Morbidity

An important metric is the relative rate of increase/decrease in morbidity compared to changes in life expectancy: goal is relative compression of morbidity

Compression of Morbidity 1980–2011: A Focused Review of Paradigms and Progress. Journal of Aging Research, 2011

Kohn1978

Is Aging a correlate or a Catalyst of Chronic Diseases?

Cardiac Hypertrophy

Metabolic Syndrome

MitochondrialDysfunction

Inflammation

CellularSenescence

ProteinAggregation

Sarcopenia

FRAILTY

AUTOIMMUNEDISEASE

TYPE II DIABETES

CARD

IOVA

SCUL

ARDI

SEAS

E

CANCER NEURODEGENERATIVE

DISEASE

STROKE

AGINGMETABOLIC SYNDROME

ARTHRITIS

Aged Related Chronic Diseases Could be Deferred

AEROBIC EXERCISE

7

DIET – Caloric Restriction

Diet & exercise, processes known to inhibit key pathways of interest (such as mTOR) have clearly shown ability to extend healthy lifespan (healthspan)◦ Stanford runners study◦ Intermittent caloric restriction

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0 20 40 60 80

Age (Cell Divisions)

Frac

tion

Viab

le

10 20 30 40

Age (days)

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0.2

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Aging Can Be Slowed: Dietary Restriction

Control

DR

ControlDR

DR

DR

Control

Control

DR also “works” in primates

CONTROL CR

Science July 10, 2009

How Diet & Exercise Work?

NutrientsGrowth Factors

EnergyStress

mTOR

Metabolism Insulin sensitivity

Neoplastic tendencies

Aging

Chronic Disease

Healthy State or Chronic Disease?

mTORC1 mTORC2

Pankaj Kapahi

The TOR Pathway

Current Biology, 2004

Science2005

Genes Dev. 2006

RAPAMYCIN

• The first, non-specific mTOR inhibitor• Approved in the US & worldwide as

– Adjunctive agent for prevention of acute renal allograft failure (Rapamune – Wyeth)– Improving coronary luminal diameter in patients with symptomatic ischemic disease

(Cypher Stent – Cordis Corporation)

• Has shown efficacy in many other disease states in mice

NIA Intervention testing program Nature 460:392

Extends Healthspan in Mice

Biochim. Biophys. Acta (2009) 1790: 1067-1074

BRAIN DISEASES(eg. HD/AD/PD)

AGING

CANCER

CARDIOVASCULARDISEASE

METABOLIC DISEASE

STROKE

Rapamycin – The First mTOR Inhibitor

Randy Strong, UTHSCSA; NIA Intervention testing program Nature 460:392

The Mice are Healthier!

Stroke

Arthritis

Wrinkles

Frailty

Heart Disease

Type IIDiabetes

CancerNeuro-degeneration

Rapamycin and Age-Related Disease

Biochim. Biophys. Acta (2009) 1790: 1067-1074.

?

A Tale of Two “Anti-Aging” Compounds

Rapamycin ResveratrolIncreases life span

(yeast, worms, flies) YES YES/NO

Increases life span (mice) YES NO

Diet-induced obesity, neurodegenerative

diseases, cancer (mice)YES YES

Efficacy in humans YES ?

Found in red wine NO YES

Thioflavin T

Alavez et al. Nature 2011

Therapeutic Approaches

• Targeted approaches to age-related diseases

- Andersen / Zeng Parkinson’s

- Ellerby / Hughes / Others Huntington’s- Dale Bredesen

Alzheimer’s- Chris Benz

Breast Cancer- David Greenberg Stroke- Kapahi / Brand Diabetes- Brian Kennedy CVD,

Progeria- Deepak Lamba Macular

Degener.- Simon Melov

Sarcopenia

Economics of Increasing Healthy Life Expectancy or ’Slowing’ CDs

• 1 QALY (Quality Adjusted Life Year) and VSLY (Value of Statistical Life Year) in US:

• 50k to 500k depending on methodology (VSLY)• 100k hospitals; 50k pharmaceuticals (QALY)• GDP per capita in US is $47K

• If we consider $100,000, a medicine that increases life by 5%, at full health and across the US population, increases life expectancy by

• ~4 years; and the corresponding dollar benefit would be:• 4 years*300 million Americans*$100,000= 120,000,000,000,000

or 120 trillion dollars!• If we consider CDs and non-CDs independent and uncorrelated:

a medicine that delays CDs (70% of morbidity/mortality rates in US) has an economic value of: 120 trillion * 0.7= $ 84 trillion

State-of-the-Art

Basic Science

Treatments for Chronic Disease

Extend Healthspan!

Prevention of

Conclusion: The Framework of the Buck Institute

Thank you. www.buckinstitute.org

Almaty 03|12| 2012

Burden of CDs-Example of Diabetes in US

• 25.8 million people in the United States (8.3% of the population) have diabetes.

• In 2010, about 1.9 million new cases of diabetes were diagnosed in people aged 20 years or older.

• If current trends continue, 1 of 3 U.S. adults will have diabetes by 2050

• Total costs (direct and indirect) of diabetes in 2007: $174 billion ~8% of total healthcare costs

• Available treatments: decrease disease evolution…

http://www.cdc.gov/chronicdisease/resources/publications/AAG/ddt.htm