almaty 03|12| 2012 the buck institute for research on aging brian kennedy, president & ceo...
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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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Age (Cell Divisions)
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Age (days)
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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