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Personalized Aging

3rd Annual Senior Living Executive courseSunday, February 26th, 2017

Dean Pinchas Cohen, MD

USC Leonard Davis School of Gerontology

Case #1

• A 60-year old man walks into a bar…

• OK, actually he walks into a doctor’s office

• He needs a general physical, and he wants to get life insurance, and he wants to start living a healthier lifestyle. Yes, its the second week of January

The “Digital-Aging” Initiative at the

USC Davis School of Gerontology

Digital Aging Center• Center Fully Launched in 2013

• Mission Defined - Partners Committed

• Leadership Established (Liz Zelinski)

• First Lead Grant $250,000 (HCP)

• First Product Launched

– (guide to elder abuse response app)

• Signature App Development Program

• A centralized source of aging and supportive technology information

• Incubate new products, programs, applications, services

• Next product to launch: the Longevity App

GEARA Guide for

Elder Abuse

Response

Digital Aging – App Competition

We hold an annual competition among our

students to create the best new “app” to benefit

older adults.

Winners included:

GEAR App

Longevity App

Call-Grandma App

Financial GEAR

Caregiver app (trilingual – Spanish & Tagalog)

All Cracked App

People Are Bad at Guessing

How Long They’ll Live

The chance

people (55-60 YO)

thought they had

of living to 75

(20-years ago)

Their actual chance people of living to 75

(20-years later)

2014 Abraham (UM) andHarris (Brookings Institution)

When the “Spans” Don’t Match…Lifespan – Average life expectancy

Healthspan – Age of contracting a chronic disease

Disability-Span is growing

“Wealth-span” – Age when savings begin to dwindle

0

10

20

30

40

50

60

70

80

90

1900 1960 2010

Mean lifespan

Mean Healthspan

Using Biology to Estimate Age & Measure Risk

• Biomarkers help determine “biological age”

• Biological age is more predictive of remaining life expectancy than chronological age

• Modifying health behaviors and environment can slow biological aging and increase longevity

Current Calculator Uses Multi-

dimensional Information Clinical Biomarkers

C-reactive Protein

Creatinine

Alkaline Phosphatase

Albumin

HbA1c

Systolic Blood

Pressure

Total Cholesterol

Sociodemographics

Chronological Age

Gender

Race/Ethnicity

Education

Health Behaviors

Physical Activity

Smoking Status

Body Mass Index

Waist

Circumference

Alcohol

Consumption

The USC Longevity app

The USC Longevity Calculator

Two Main Features

1. Predicts current life expectancy

2. Incentivizes adoption of healthy

lifestyle to improve life expectancy

Using the

Longevity

App to

motivate

people to

make lifestyle

changes

78 yrs84 yrs

Case #1.1

• The man selects an appropriate life insurance policy (projecting a life expectancy of 88 (80%)

• Appropriate medical therapy initiated

• Diet and exercise program initiated

• Longterm care insurance is recomended

Centenarians• I950 - 5,000 centenarians world-wide

• 2000 - 250,000 centenarians world-wide

• 2015 – 600,000 in China alone

• 2050 - 6 million centenarians world-wide

• Exceptional longevity is hereditary – choose your parents well

• Multiple genes associated with longevity have been identified

• Genes also control your response to diets and meds

• Potential diagnostic tools and therapeutic targets

100 years later

Gender and AgingWomen

• Lived only 1-2 years longer a century ago

• Live 5 years longer than men today

• Represent >75% of centenarians

• Spend more years with “disability”

Source: Crimmins and Colleagues, PNAS 2015

• A 58 year old women brings her mother to a memory care facility.

• She is happy with the set up and the care but displays anxiety related to her mothers diagnosis of Alzheimer’s disease

• During the interview with the resident physician she asks of her own risk

Case #2

Personalized Aging

My other main initiative for the USC

Davis School involves something I call

“personalized aging.”

Some of you may have heard of

“genomics” and some of you may

have not.

Basically, everybody ages differently

due to many factors unique to the

individual, including our genes.

THE USC CENTER FOR PERSONALIZED AGING

• Filter out non-relevant health messaging

• Allow focus on areas of personal highest risk

• Help select individualized programs, diets,and wellness strategies

The end of “one-size-fits-all”

aging advice

PERSONALIZED AGING INITIATIVE

The opportunity:

• Create new approaches to individualized strategies for health

maintenance which could be referred to as "personalized aging”

• Abandon 20th Century advice – “one-size fits all”

• Capitalize on novel technologies and Genetic Counseling:

• Diet and nutrigenomics

• Health telemetry

• Exercise innovation and wearable tech

• Brain Training – apps and beyond

• Develop a paradigm by which personalized longevity advice can

be offered to people together with appropriate nutritional,

exercise, brain training and tailored pharmacological interventions

The Evolution of GenomicsGenomics 1.0 – Discovery of Disease-Related Mutations

Rare conditions, e.g. Sickle Cell, Huntington’s Disease, Cystic Fibrosis

Genomics 2.0 – Identification of Disease SusceptibilityCommon conditions, e.g. Diabetes, Cancers, Alzheimer’s

Genomics 3.0 – Responsiveness to TreatmentsCommon conditions, e.g. Diabetes, Cancers, Alzheimer’s

Genomics 4.0 – Genetics of PreventionIdentifying genetic variants that determine responsiveness

to diets, exercise, supplements, etc.

Creating healthy aging strategies for each individual

Cost of Sequencing One GenomeFrom $3,000,000,000 .... to < $3,000

H

Heritability

Height heritability – 80% (>400 genes)

Knowing an individuals’ risk level may…

• Lead to more targeted interventions

• Incentivize at-risk individuals to improve their health

How do you discover risk genes? 2005-2015?

Genome-wide association analysis

GWASInvolves genotyping cases and controls for >1,000,000 SNP markers spread throughout the genome and looking for associations between genotypes at any locus and disease status.

Single-nucleotide polymorphismwe have tens of millions

23&me$199

Provides information on >2,000,000 SNPs

å

Average Alzheimer’sLifetime Risk

ApoE e4/e4 Alzheimer’sLifetime Risk

APOE

Allele rs429358 rs7412

OR vs.

Ave

OR vs.

e3/e3

ε2/ε2 TT TT 0.26 0.5

ε2/ε3 TT TC 0.36 0.6

ε2/ε4 TC TC 1.38 2.5

ε3/ε3 TT CC 0.56 1

ε3/ε4 TC CC 2 3.5

ε4/ε4 CC CC 7.71 8

• The Women’s APOE genotype is e4/e3

• Her AD risk is 3-fold elvated

• Exercise, weight loss, vegetarian diet, and various forms of brain training are recommended

• Her sister is referred to testing as well

Case #2.1

• 59 year old hypochondriac discovers 23andMe

• Has great concerns about family history of coronary disease

• Has stressful job, travels frequently on business, and has limited time to exercise.

Case #3

My Genomics at 23and Me

Pinchas Cohen, M.D.23&Me Results

Thromboembolism Risk

• Reality check

• Longevity app predicts 80-84 years

• Changes travel style (Business Class, compression stockings)

• Aspirin, 10,000 steps, aspires to be a vegan

Case #3.1

N-acetyl-transferaseregulates metabolism of

overcooked meatfast vs. slow

POT1 – the sunscreen gene

After a two year loan to the United States, Michelangelo's David is being returned to Italy:

2014 USC Diet Studies Challenge Thinking on Proteins Versus Carbs

Caloric RestrictionExtends Lifespan?(only sometimes)

Dis-lipidemiaNoYes

PersonalizedAging!!!

What diet should you be on?

For $30,000,000,000

And 20-years

We can tell you!

Low Calorie?Low Carb?Low Fat?Low Protein?Mediterranean?Vegetarian?Vegan?

Big Genomics

What can we do to reduce our genetic risks:

Based on the individual susceptibility –

Avoid smoking and Obesity

Exercise

Select an appropriate diet

Carrot is the new Hotdog

USC Davis School of Gerontology Graduate Coordinated Program in Dietetics

• Master’s of Science Degree in Nutrition, Health-span

and Longevity (NHL) Focus on Nutrigenomics

• Graduates can sit for the exam to become Registered

Dietitians (RDs)

• Focus on medical nutrition therapy, community

nutrition, food science, policy and leadership

• Translating nutrition research into practice

• Will be a one-of-a-kind program in the world

• First students started in 2014 - will graduate this year

Wearable Tech: Personalized Exercise

Non-invasive brain stimulation

Brain Training – for those with dementia risk

Brain-Challenging Video Games

What can we gain from cognitive interventions in healthy older adults?

• Attempt to prevent a decline in cognitive tasks

• Rehabilitate and improve declining cognitive skills

• Ensure preservation of functional ability Image courtesy of http://www.simpsoncrazy.com/pictures/homer

Personalized Health Services

• Individual exercise regimens

• Nutrigenomic analysis and customized diets

• Brain training exercises

• Stress reduction (spirituality, social engagement)

“Nonsense, Dad - you look fabulous!”

The Economic Benefits of Prevention

212323

54160

0

200

400

600

800

1000

2010 2020 2030 2040 2050

Total Medical Costs ($Billions) for Individuals with Alzheimer’s Disease under delay scenarios

Total Costs ($Billions) Delay 1 Year Delay 5 Years

928

593

300

518

214

119

Zissimopoulos and Crimmins 2015

Final Secret to a long and Healthy Life:

• Everything in Moderation

• Including moderation

Personalized Health and Longevity