Donald A. Jurivich, DO E. Gilbertson Distinguished Professor of Geriatrics Chairman, Department of Geriatrics UND School of Medicine Consultant, Sanford Health – Fargo

2016 Healthy Longevity Presentation:

Prescription for healthy aging 

Destress, don’t try to fix what you can’t fix

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Eat veggies / grains / fruits

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Eat less

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Be socially supportive and supported

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Reduce sedentary time. Exercise

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Repeat: exercise (in addition to house work), doing both aerobic and weight lifting

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Be flexible, such as yoga for sleep quality

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Maintain a life mission

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Laugh 100 times a day

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Talk disclosures Internal Medicine and Geriatric Medicine physician Professor and Chairman of Geriatrics University of North Dakota Sanford Healthcare

HEALTHY LIFESPAN

Research on Aging and Cell Protection

Dr. Donald A. Jurivich Eva Gilbertson, MD Distinguished Professor of Geriatrics University of North Dakota

Presentation goals Define global aging demographics

Consultant to NIH – NIA Past board member, American Geriatrics Society

I have lost my sight, smell, hearing, taste and touch. How should I use them for your closer contact ? --TS Eliot, Gerontion 1920

Report biologic determinants of aging and longevity Describe healthy lifespan interventions Summarize progress with age – dependent chronic conditions

1936

2016

103 year old Dexters from Iowa celebrate 80 year marriage

Explain future directions in health and aging

New World explorer, Ponce De Leon searched for :

Active Learning exercise  List how long you think you will live (age)

and if given a fountain of youth pill, how long you would like to live in good health (age).

A. Gold B. Spices C. Fountain of youth

 List one thing you do to promote healthy 0%

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D. Plant medicinals

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E. New trade routes Sp ice s

longevity. Rank 1 – 5 how well you do this with “5” being “you nailed it.”

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French Supercentenarian Jeanne Louise Calment 122 years, 164 days.

The oldest recorded human age is ? A. 116 B. 117 C. 118 D. 120 E. 122

Sakhan Dosova, a Kazakh woman may be a recordsetting 130 years old.

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Global trends in Aging

What percent does Genetics contribute to longevity ? A. 25 % B. 33 % C. 50 % D. 75 % E. 90 %

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“Oldest – old” are the fastest growing population globally

4.5 million U.S. baby boomers turning 65 years old annually since 2011

USA elderly population distribution Grand Forks, North Dakota

2005  2050 percent increase in different age groups

Expect 18% by 2020 Source: UN Dept of Econ and Social Affairs

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Life expectancy varies between and within nations

The rate of population aging varies between nations Time required to go from 7 to 14 percent of population 1860 1880 1900

1920

1940 1960

1980 2000

2020 2040

Chinese longevity skewed to coastal areas

What are health implications for global shifts in older adult populations ? Increasing functional disability More chronic disease burden Higher health & medication costs Inadequate “aging in place” resources Fewer family care givers Vaccination costs & access (zoster, pneumonia, influenza) New infection source (re-activation TB) Increase elder abuse & neglect

Where do men outlive women ?

When do age – dependent changes manifest ?

A. Galapagos islands

A. 20 years old

B. Japan

B. 30 years old

C. Sardinia

C. 40 years old

D. Nova Scotia

D. 50 years old

E. Jamaica

E. 60 years old 0% 0%

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Biology of Aging: Cure aging to avoid chronic disease

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The Aging Process: functional lifespan

Human aging starts ~ 20 years old

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FUNCTION (%)

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75

50 Successful Usual

25

Accelerated 0

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25

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AGE

What are the biologic drivers of longevity ?

Aging and Homeostasis Disturbed Disease

Death

function

Normal function maintained without significant cost Limit of compensatory processes

Doris Lane Grey

 Genetic factors  Loss of homeostasis

Failure

Permanent disability

 Environment

Treatment

Breakdown

Compensation

homeostasis

Prevention

Normal adjustment

Health

Adapted from Physiological Basis of Aging and Geriatrics Paola Timiras

Genetics of longevity

Animal models of Exceptional Lifespan Nature (2001) 414, 412

 Danish twin study: 25% inheritability

metabolism  Centenarians have disease resistance

genes

Maintenance

 Longevity genes parse with lipid

Disease Avoidance Brain Learning / Memory Immune system functionality Skeletal and joint integrity

Ames mouse

Wild type mouse

Cancer Osteoarthritis Diabetes Dementia Kidney failure Cataracts

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Long lived mice versus human longevity factors

Socio-economic status affects longevity

Mice

Human

Hormone system disrupted:  No GH or TSH

Absolute hormone deficiencies are detrimental to health

Low body temperature

Glasgow Center for Population Health  Accelerated telomere shortening if

 Income less than L25,000  Low vegetable diet  Home rental

Centenarians: reduced insulin / IGF1 signaling Elevated TSH

Healthy Longevity interventions

Caloric Restriction to prolong life ?

 Nutrition  Caloric Restriction

 Activate longevity - linked pathways  Metabolic and Stress Genes

 Physical activity Roy Walford, MD

 Suppress aging accelerant pathways  DNA methylation, IGF1 signaling

 Supplements

 Controversies  Not all animal models benefit from CR  Intermittent versus continuous CR  Total calorie versus protein restriction  Exercise plus caloric restriction shortens life !

In addition to extending lifespan, caloric restriction results in:

Eating to break 100 ?

A. Higher infection rates B. Lower body temperatures C. Lower cancer rates D. Changes in insulin levels E. All the above ra te s ct io n

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Blue Zone connection of diet to exceptional longevity

Global exceptional longevity

Sardinia

Sheep cheese high omega oil

Cannonau red wine 3 x flavinoids

Goat milk curry leaf factors

Odds Ratio for CV events

Added years to life expectancy

Loma Linda, California vegetarian diet

8 6 4 2 0 1 Omni

Ovo

Okinawan longevity diet

1 0.8

Caloric restriction in addition to a DASH or Mediterranean type of diet

0.6 0.4 0.2 0 women

men

Vegan

Adventist I and II Studies

Centenarian Diets

Costa Rican longevity diet Nicoya Peninsula 300% increase in centenarians Longer telomeres than mainland residents High legumes (beans) High calcium (tortillas and water) Fruits and veggies

Meat Sardinia

+

Okinawa Costa Rica Loma Linda

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Fish

Milk / cheese

Beans

Vegies

+

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Fruits ++++

Grains ++++

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Longevity extension through chemistry ?

Agents to increase lifespan  Resveratrol  Rapamycin  Metformin  Vitamins  Herbals  Nicotinamide Ribose (NAD)

Role of vitamins in longevity ? 60

40 30

vitamin A vitamin E

20 10

B. Vitamin B12 C. Biotin

> 100

Free Radical Biology and Medicine 28:1243-1248, 2000

D. Vitamin E

Centenarians exhibit high anti-oxidant vitamins in their serum

Meta-analysis: Vitamin E supplementation may decrease lifespan

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Which vitamin supplement has been reported to increase elderly mortality and shorten lifespan ?

Vitamin supplementation  Vitamin D  RCT showed all causes of cancer reduced in 50+

y/o taking Vitamin D supplementation (RR = 0.6) Am J Clin Nutr 2007;85:1586 –91

 Vitamin C  RCT show no harm or benefit

 Multi vitamin supplements  RCT show no harm or benefit

 High dose B complex  Pilot study suggested effect in prevention MCI Annals Internal Medicine 142:37-46, 2005

conversion to dementia  Concern: renal failure

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Hormone replacement therapy for longevity ?  Estrogen for women: not recommended  U.S. Womens Health Initiative showed substantial

worse health outcomes with HRT. 

 Androgen for men: not recommended  Growth hormone: side effects

Stem Cell Therapy Muscle stem cells injected into old SAM from young mice extended lifespan 3 – fold. Growth Differentiation Factor 11 reconstitutes brain, muscle & heart in old mice, and the factor declines with human aging Oxytocin therapy

Nicotinamide Ribose

Physical inactivity accelerates aging processes

Precursor to Nicotinamide Adenine Dinucleotide (NAD) NAD pool in mitochondria decline with age Consequence: lower ATP levels and diminished mtDNA and bioenergetics. Restoration of NAD levels reverses age – dependent mitochondrial dysfunction

Telomere length is reduced by aging and inactivity

Healthy longevity through exercise 65 year old

Healthy Life Expectancy

Years gained

No exercise

77.7 years old

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Exercise

83.4 years old

5.7 years

PLOS 2012 Exercise intensity (MET – h/wk)

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How can we measure our anti – aging efforts ?

How much exercise is enough ?

 Physiologic measurements  Function  Biologic

Intensity

Low Moderate Intense

Duration (minutes)

Benefit (% CV risk reduction) 10 20 – 30 40

30 60 90

 Psychological measurements  Happiness  Sense of purpose

Alberto Giacometti

Gait speed is a biomarker of health outcomes

Gait speed in elderly strongly predicts A. Falls B. Cognitive Impairment C. Life span D. All of the above

Measuring anti – aging efforts

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Biomarkers of inflammation  Inflammaging  Elevated serum cytokines  Interleukin 6  CRP  TNF receptor  Hsp 70

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Chronic conditions increase 1% annually in synchrony with the Silver Tsunami Percent of population

People with chronic conditions (million)

Where do we go from here ?

Dale Jackson

Diabetes increases with age Global variation in diabetes prevalence

Dementia is a Global problem • Mediterranean diet prevents brain shrinkage • Southern Asian Indian food linked to neuroprotection from AD

Income disparities

Brain failure and politics: Identify U.S. Republican politicians with Alzheimer’s Dementia…………..

Quick facts about D.T.

1. D.T. is a medical abbreviation for Delirium Tremens

A. Donald Trump (a.k.a., John Baron) B. Ronald Regan (a.k.a., The Gipper) C. Barry Goldwater (a.k.a., Mr. Conservative)

2. Delirium Tremens is a Belgium ale with a pink elephant logo and described by the brewery as: “The aftertaste is strong, long-lasting and dry bitter.”

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Compounds to prevent or reverse brain failure

Curcumin as a diagnostic agent: binds to amyloid plaques in retina

Global Health insights to dementia and putative effects of curcumin India

US

70 -79 year old

o.7 %

3.1 %

80 + year old

4.0 %

15.7 %

normal

No differences in ApoE4 expression amyloid Neuroimage. 2011 January ; 54S1: S204–S217

Finding the cure for Alzheimer’s Disease is challenging

If not a cure, then slowing the onset and progression of AD has value

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Dementia treatments based on Mechanism of Action Receptor modulators Acetylcholinesterase NMDA Muscarinic 5-HT

Social - economic determinants of longevity ? Functional support

Housing

Proteotoxicity and Plaque busters Beta amyloid inhibitors Amyloid synthesis inhibitors Chaparones (hsp 70)

Financial support

Ion channel / Chelation / Young plasma Vaccines / Immunotherapy Neuroprotection

Shifts from family – based to institutional based care giving or alone.

Inadequate resources for care in late life:

2014 Retirement Confidence Survey

Japan

60 % of US Workers (18 – 64 years old) saved less than $25,000 for retirement Total savings & investments by workers: 

$ 218,000 health care costs per couple per 20 year retirement span

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Retirement span to increase

www.ipss.go.jp/p-info/e/psj2008/PSJ2008-07.xls

Housing needs for cognitively impaired elderly Elder care tech industry.  sensors  pillbox sensor  pill biochips  reminders  surveillance (granny cams)  Nanoparticle therapy

< $1000

36%

< $10,000

16%

< $25,00

8%

Gero – Smart Technology Percent achieving BP goal 90 80 70 60 50 40 30

Dementia prevalence in Australia

20 10 0 Usual

Biochip

Proteus Discover

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Dashboards of personal health from Biometric monitors Pharmaceuticals: Anti – aging agents Biologics Alz Disease meds

Cloud – based EMR SMART Technology Senior Housing

TIME

Sanford Health • Biomarkers of aging

Industry

UND • Cell protection

• Population health

• Epigenetics

• Imagenetics

• Longevity • Alz Dx Health systems

Current Odds of living to 100 are 1:4000 Royal Flush 1:3900

Children born currently have a projected odds of 1:4 for living to 100 years old.

University

Prescription for healthy aging     

Destress Longevity diets Eat less Social support Reduce sedentary time / exercise  Both aerobic / resistance  Flexibility (yoga) for sleep quality

 Maintain a life mission  Laugh 100 times daily

Goals / Questions Is the cure for aging a solution for chronic disease ? When does the prescription for longevity start ? How do we create a culture for long healthy lives ?

How do we change behavior to recognize long term and cumulative effects of poor life habits ?

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