slide1
Download
Skip this Video
Download Presentation
The Utah Study of Fertility

Loading in 2 Seconds...

play fullscreen
1 / 43

The Utah Study of Fertility - PowerPoint PPT Presentation


  • 448 Views
  • Uploaded on

Initiative to Study Exceptional Longevity. Advisory Panel on Exceptional Longevity (APEL) ... factors that contribute to exceptional longevity (EL) and reduce risks across major ...

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'The Utah Study of Fertility' - Kelvin_Ajay


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

The Utah Study of Fertility, Longevity & Agingand the Utah Population DatabaseKen R. Smith([email protected])

Supported by NIA grants AG00767, AG14495, and AG13478.

longevity game northwestern mutual
Longevity Game – Northwestern Mutual

Gender

Age

Family History

BMI

Blood Pressure

Stress

Exercise

Diet

Seat Belt

Driving Style

Alcohol

Smoking

Illicit Drug Use

http://www.nmfn.com/tn/learnctr--lifeevents--longevity_end

longevity calculator new england centenarian study
Longevity Calculator - New England Centenarian Study

Tobacco

Diet

Alcohol

Air pollution

Coffee/tea

Aspirin

Flossing

History of CVD

Tanning

Social Support

Stress

Family Hx

of Longevity

Exercise

Vitamins

Gender

Age

traditional method
Traditional Method
  • Life Tables
  • Gender
  • Age
  • Place
  • Year
objectives
Objectives
  • Why study exceptional familial longevity?
  • NIA support
  • Utah Longevity Study
  • Measures
  • Importance of the Utah Population Database
  • Research Highlights
  • Final thoughts
slide13
LONGEST LIVED

HUMAN WITH

AUTHENTICATED

RECORDS

Jeanne Louise Calment,

Paris

Died 1997 at age 122

LONGEST LIVING

HUMAN WITH

AUTHENTICATED

RECORDS

116-year-old

Elizabeth “Lizzie” Bolden.

Memphis, Tenn.

slide14
What allowed these individuals to live so long?

Aged slowly & thus avoided serious fatal diseases

Science, 2-28-2003

national institute on aging initiative to study exceptional longevity
National Institute on AgingInitiative to Study Exceptional Longevity
  • Advisory Panel on Exceptional Longevity (APEL)
    • Find genetic & environmental factors that contribute to exceptional longevity (EL) and reduce risks across major age-related diseases
    • Find homogenous subgroups that comprise the long-lived population (e.g., familial patterns of longevity)
u tah s tudy of f ertility l ongevity and ag ing usflag national institute on aging
Utah Study of Fertility, Longevity, and Aging (USFLAG) (National Institute on Aging)

2

Resistance to chronic diseases and environmental stressors

Rank UPDB pedigrees

in terms of family pattern of longevity past 65

Psycho-social, biological, genetic markers associated with exceptional survival among relatives around age 90+

3

1

  • Do offspring of long-lived parents age more slowly than controls

4

selected measures
Demographic Factors

Risk/Lifestyle Factors

Medical History

Reproductive History

Cognitive Functioning

Instrumental/Activities of

Daily Living

Depression

Stress Resiliency

Blood Measures

Serum Cholesterol

Glycosylated Hemoglobin

C-reactive protein

DHEA/DHEAS

Albumin

Uric Acid

Creatinine

WBC

DNA

Immortal cell lines

Genome Wide Scan

Telomere Length

Mutations in mtDNA

APOE

Clinical Measures

Grip Strength

Blood and Pulse Pressure

Heart Rate

Lung Function

Body Mass Index

Body Temperature

Morbidity

(CMS Medicare claims)

Mortality (cause of death)

Selected Measures
aging research advances through novel linkages to updb
Aging Research Advances ThroughNovel Linkages to UPDB

Centers for Medicare &

Medicaid Services

1991-2002

400,000 Utahns

age 65+

Cache County Study on

Memory, Health & Aging

Ron Munger, JoAnn Tschanz, Maria Norton

USU

Kathleen Welsh-Bohmer

Duke

slide22
Does Exceptional Survival Run in Families?Does a Family History of Extreme Longevity Protect Against Major Age-Related Diseases?
slide23
Recurrence Risks of Extreme Longevity (Lived Past 99th Percentile of Excess Longevity) in Various Classes of Relatives (UPDB)

Extreme Longevity Runs in

Families

Parent, Sibling

Gparent, Gchild, Aunt, Uncle,

Niece, Nephews

1st Cousin

Once Removed

1st Cousins

Kerber, O’Brien, Smith and Cawthon, 2001, J of Gerontology

relative risk of mortality top 25 vs bottom 25 of familial longevity updb
Relative Risk of Mortality:Top 25% vs. Bottom 25% of Familial Longevity (UPDB)

Extreme Familial Longevity

Reduces Risk at Most Ages

Worse

Cancer

Cerebrovascular

Diabetes

Better

Heart

Age

O’Brien, Kerber, Smith, Mineau, submitted, 2006

slide25
Are there factors that we can observe in midlife (age 50) in UPDB that predict lower mortality in later years?The case of late female fertility(or if you can measure it, late natural menopause)
slide26
Relative Risk of Living to 100

Vs. Dying Before Age 85 Among Women By Age at Last Birth

(Among Women Surviving to Age 60; Born <=1900) (UPDB)

Late Fertile Women

More Likely to be Centenarians

Relative Risk

Age at Last Birth

Controls for Mormon/Non-Mormon status, birth year, parity, age at first birth

Reference group: Women whose Age at Last Birth is 37 to 42 years of age

Smith, Mineau, Bean, Social Biology, 2002

slide27
Reduced Risk of Mortality from Leading Causes of Death Among Females (60+) with Very Late Fertility (>age 45) vs. Controls (UPDB)

Late Fertile Women

Less Prone to Major

Causes of Death

slide28
Relative Risk for Late vs. Average Age (<=41) at Last Birth Between Female Members 55 or Older of Lineages Selected for Exceptional Longevity & Control Lineages

>=3 Probands per Lineage

8.9

Women from LL Pedigrees are

More Prone to be Late Fertile

Adjusts for birth date, age at first birth, LDS affiliation; Bars represent 95% CI; N=440; All subjects lived to age 55.

slide29
Relative Risks for Mortality for Brothers Living to Age 50 byMaximum Age at Last Birth of Sisters Who Survived to Age 50(Reference Group: Sisters’ with Max Age at Last Birth below 50th Pct)

Brothers of Late Fertile Women Live Longer

Relative Risk

UT = Utah Population Database (n=29,445 males)

slide30
Telomeres and Longevity

As cells divide, telomeres shorten with increasing age due to a decline in the enzyme telomerase

Short telomeres trigger cell death & cellular senescence (possibly as a protection against cancer) and are associated with aging and death

UGRP (Utah Genetic Reference Project) families linked to UPDB

those with longer telomeres in blood dna live longer among the elderly controlling for age
Those with longer telomeres in blood DNA live longer among the elderly, controlling for age

Years Since Blood Draw

Cawthon, Smith, O’Brien, Sivatchenko, Kerber, Lancet, 2003

slide32
Women

Men

Years Since Blood Draw

Cawthon, Smith, O’Brien, Sivatchenko, Kerber, Lancet, 2003

slide33
Age 60-74

Age 75+

Cawthon, Smith, O’Brien, Sivatchenko, Kerber, Lancet, 2003

relative risk of disease offspring of proband vs controls
Relative Risk of Disease: Offspring of Proband vs. Controls

Odds Ratio

69 offspring

1569 NHANES controls

Controls for age, gender, education, marital status

genetic markers associated with aging and survival that are linked to the updb
Genetic Markers Associated with Aging and Survival that are Linked to the UPDB
  • ε4 allele:
    • Risk of cardiovascular disease
    • Alzheimer’s Disease
  • ε2 allele
    • More frequent in centenarians
  • Association between APOE genotype and cause-specific mortality
    • Modified by indicators of rates of aging
    • Possible because of record linkage to UPDB
mortality rate ratios for apoe genotypes 33 is reference
Mortality Rate Ratios for APOE Genotypes (ε33 is reference)

All-Cause

Cardiovascular (633)

ε22 ε23ε24 ε34 ε44

ε22 ε23ε24 ε34 ε44

Respiratory (176)

Cancer (249)

ε22 ε23ε24 ε34 ε44

ε22 ε23ε24 ε34 ε44

mortality rate ratios for apoe genotypes 33 is reference39
Mortality Rate Ratios for APOE Genotypes (ε33 is reference)

Nervous (AD, Parkinson) (84)

Endocrine (Diabetes) (62)

ε22 ε23ε24 ε34 ε44

ε22 ε23ε24 ε34 ε44

Digestive System (57)

Mental Disorders (42)

ε22 ε23ε24 ε34 ε44

ε22 ε23ε24 ε34 ε44

effects of apoe genotype on all cause mortality by familial longevity
Effects of APOE Genotype on All-Cause Mortality by Familial Longevity

Pedigrees of Average Longevity

Long-Lived Pedigrees

ε22 ε23ε24 ε34 ε44

ε22 ε23ε24 ε34 ε44

Interaction between FEL and ε34 & ε44, p<.05

medicare claims
Medicare Claims
  • 65-69 year olds (n=28,000)
  • 1998-2002
  • Medicare Claims in Utah
  • Compare top 10% for familial longevity to the rest
    • 11.2 fewer claims
    • 8 fewer claims for heart disease, stroke, cancer, and diabetes combined
    • 40% more likely to have made no claims for these four leading conditions
final thoughts
Final Thoughts
  • Study not designed with personalized medicine in mind
  • Potential for identifying measures that capture rates of aging that predict risks from multiple diseases
  • Long-lived as a source of information about low disease risk
  • Value of deep family history of longevity to supplement family medical history
  • Value of UPDB
usflag team
Genetics and Genetic Epidemiology

Richard Cawthon

Richard Kerber

Elizabeth O’Brien

Demography

Geri Mineau

Ken Smith

Biostatistics

Ken Boucher

Gilda Garibotti

Psychology

Cindy Berg

Project Manager

Diana Lane Reed

Database Manager

Alison Fraser

Project Coordinators

Heather Anderson

Jahn Barlow

Database Linkage/Programmers

Richard Pimentel

Heidi Hanson

Study Coordinator

Michelle Robinson

Phlebotomists

Kellie Littlefield

Jayci Bash

Layah Steinberg-Moss

Informatics

Dinny Berry

Research Administration

Camille Phillips

CRC

Sayed Ahmed

USFLAG Team
ad