![Page 1: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/1.jpg)
Almaty 03|12| 2012
The Buck Institute for Research on Aging
Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy
![Page 2: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/2.jpg)
• 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
![Page 3: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/3.jpg)
CDs: Heart, Stroke, Hypertension, Lung, Mental, Diabetes & Cancer
December 13th, 2003
The shape of things that are here! December, 2011
![Page 4: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/4.jpg)
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
![Page 5: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/5.jpg)
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
![Page 6: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/6.jpg)
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
![Page 7: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/7.jpg)
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
![Page 8: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/8.jpg)
0
0.2
0.4
0.6
0.8
1
0 20 40 60 80
Age (Cell Divisions)
Frac
tion
Viab
le
10 20 30 40
Age (days)
0
0.2
0.4
0.6
0.8
1
0
Frac
tion
Viab
le
Aging Can Be Slowed: Dietary Restriction
Control
DR
ControlDR
DR
DR
Control
Control
![Page 9: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/9.jpg)
DR also “works” in primates
CONTROL CR
Science July 10, 2009
![Page 10: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/10.jpg)
How Diet & Exercise Work?
NutrientsGrowth Factors
EnergyStress
mTOR
Metabolism Insulin sensitivity
Neoplastic tendencies
Aging
Chronic Disease
Healthy State or Chronic Disease?
mTORC1 mTORC2
![Page 11: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/11.jpg)
Pankaj Kapahi
The TOR Pathway
Current Biology, 2004
Science2005
Genes Dev. 2006
RAPAMYCIN
![Page 12: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/12.jpg)
• 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
![Page 13: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/13.jpg)
Randy Strong, UTHSCSA; NIA Intervention testing program Nature 460:392
The Mice are Healthier!
![Page 14: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/14.jpg)
Stroke
Arthritis
Wrinkles
Frailty
Heart Disease
Type IIDiabetes
CancerNeuro-degeneration
Rapamycin and Age-Related Disease
Biochim. Biophys. Acta (2009) 1790: 1067-1074.
?
![Page 15: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/15.jpg)
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
![Page 16: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/16.jpg)
Thioflavin T
Alavez et al. Nature 2011
![Page 17: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/17.jpg)
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
![Page 18: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/18.jpg)
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
![Page 19: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/19.jpg)
State-of-the-Art
Basic Science
Treatments for Chronic Disease
Extend Healthspan!
Prevention of
Conclusion: The Framework of the Buck Institute
![Page 20: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/20.jpg)
Thank you. www.buckinstitute.org
Almaty 03|12| 2012
![Page 21: Almaty 03|12| 2012 The Buck Institute for Research on Aging Brian Kennedy, President & CEO Presented by Joseph Antoun, Pr. of Health Policy](https://reader037.vdocument.in/reader037/viewer/2022110206/56649ceb5503460f949b5ef0/html5/thumbnails/21.jpg)
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