Its all down hill after...

20 30 40 50 60 70 80

age (years)

Physiologic Changes Associated with Aging

Why Distinguish Normal vs Disease?

avoid harm educate patients health behavior counseling public health prognosis and care planning

“Senile” - relating to old age

senile dementia senile cataracts arcus senilis senile emphysema senile osteoporosis age-related macular degeneration

Definition of Aging

A ubiquitous intrinsic biologic process with a progressive, predictable, inevitable evolution and maturation of an organismuntil death

Not the accumulation of diseases

Defining Normal

rate of change in the process of aging mean or average value from healthy people a Gauassian distribution within the normal range

2 standard deviations

Aging and Variation

The physiologic differences betweenold individuals is greater than between young individuals

There may be greater difference within an aged cohort than betweenthe means of young and old cohorts

Young and Old Cohorts

youngold

Standard Deviation vs Percent Predicted

200

225

250

275

300

325

350

375

400

0 10 20 30 40 50 60 70 80

age (years)

Acceptable lower limit70% of predicted

Standard Deviation vs Percent Predicted

200

225

250

275

300

325

350

375

400

0 10 20 30 40 50 60 70 80

age (years)

2 Standard Deviations

Studies of Normal Aging

assume achieved maximal development age as an exposure

absence of disease absence of risk factors for disease absence of occult symptoms or signs of disease

recruitment and maintenance consent

Age-physiology Study Design

Cross-sectional

cohort born 1920-29vs

cohort born 1930-39vs

cohort born 1940-49

Longitudinal

cohort born 1920-29

measure @ time 1

measure @ time 2

measure @ time 3

Cross-sectional Cohort

enroll more patients only method for invasive data cohort effect retrospective

lack of exposure or risk factors age-associated not rate of change

Cohort Effect

height infectious exposure

influenza epidemic polio

environmental exposure pollution fluoride milk intake

Cohort Effect Bone Mineral Density

0 10 20 30 40 50 60 70 80 90

age years

Bon

e D

ensi

ty

healthy normal

Cohort Effect Bone Mineral Density

0 10 20 30 40 50 60 70 80 90

age years

Bon

e D

ensi

ty

healthy normal

rickets

Cohort Effect Bone Mineral Density

0 10 20 30 40 50 60 70 80 90

age years

Bon

e D

ensi

ty

healthy normal

rickets

anorexia nervosa

Cohort Effect Bone Mineral Density

0 10 20 30 40 50 60 70 80 90

age years

Bon

e D

ensi

ty

healthy normal

rickets

anorexia nervosa

hyperthyroidism

Rate of Change

0

50

100

150

200

250

300

350

30 35 40 45 50 55 60

Age (years)

Rate of Change

0

50

100

150

200

250

300

350

30 35 40 45 50 55 60

Age (years)

-20 per year

LongitudinalRate of Change

0

50

100

150

200

250

300

350

30 35 40 45 50 55 60

Age (years)

-5 per year

Cross-sectionalDifference in Level

0

50

100

150

200

250

300

350

30 35 40 45 50 55 60

Age (years)

Longitudinal Cohort

expensive years for data changes in technology changes in disease classification invasive testing temporal order

absence of other exposures

Longitudinal Data Points

0

50

100

150

200

250

300

350

0 1 2 3 4 5

Time

n = 1

Longitudinal Data Points

0

50

100

150

200

250

300

350

0 1 2 3 4 5

Time (years)

n = 1

Longitudinal Data Points

0

50

100

150

200

250

300

350

0 1 2 3 4 5

Time (days)

n = 1

Tissue and Cellular Changes

atrophy hyperplasia hypertrophy dilatation loss elastin loss collagen calcification

Brain

Cross-section MRI Brain Findings

nondemented independently functioning no medical illness

including HTN no medications no previous evaluation for cognitive changes

young-old (77 years) vs old-old (89 years)

JAGS 1999;47:330

Cross-section MRI Brain Findings

age-associated decrease brain volume/intracranial volume r = -.72 (p = 0.001)

age-associated increase periventricular signal r = .45 (p = 0.001)

JAGS 1999;47:330

Cardiac

Baltimore Longitudinal Study

exclusion criteria CAD BP > 140/90 valvular heart disease LVH by ECG

inclusion criteria sinus rhythm ETT negative normal wall motion and EF >50% on GHPS

Circulation 1977;56:273

BLSA Resting Echocardiogram

no change with age resting HR LV ejection time LV chamber size EF

Circulation 1977;56:273

BLSA Resting Echocardiogram

age-associated increase aortic root diameter LV wall thickness late diastolic filling

Circulation 1977;56:273

Diastolic Changes

Young

diastolee a

Diastolic Changes

Old

diastolee a

Diastolic Changes

Old

Young

diastolee a

BLSA Resting GHPS

no change with age cardiac output HR EDV or ESV EF

age-associated increase systolic BP

Circulation 1984:69:203

BLSA GHPS Exercise 100 watts

no change with age cardiac output EF peak systolic BP

Circulation 1984:69:203

BLSA GHPS Exercise 100 watts

age-associated increase EDV ESV overall increase SV

age-associated blunted peak HR response

Circulation 1984:69:203

BLSA Conclusions

CO maintained w/exercise despite lower HR

SV increased by increasing preload

?loss intrinsic contractility ?loss of sympathetic tone ?loss of ß-receptor function

BLSA Catecholamines with Age

at rest epinephrine increased

exercise epinephrine increased norepinephrine increased

J Appl Physiol 1985;59:1033

Beta-adrenergic Receptors

receptor density ? lymphocyte models decreased in explanted hearts

agonist binding affinity G protein-adenylate cyclase uncoupling

Circulation 1994;90:1225

Frank-Starling

LV-EDP (mm Hg)

Car

diac

Out

put (

L/m

in)

geriatric

young

Frank-Starling

LV-EDP (mm Hg)

Car

diac

Out

put (

L/m

in)

geriatric

young

+ inotrophic state

Clinical Application with Age

dependent on late diastolic filling tachycardia atrial arrhythmia

volume sensitive syndrome of heart failure

without significant heart disease

Pulmonary

Lung Histologic Changes

calcification cartilage ribs/spine/airways decreased parenchymal collagen airspace dilatation

Airspace Size with Age

surgical or autopsy n=38 lifelong nonsmokers 21-93 years old histology by electronic scanner airspace: surface area/volume

Thorax 1993;48:39

Airspace Area/Volume vs AgeThorax 1993;48:39

0

5

10

15

20

25

age years

airs

pac

e su

rfac

e ar

ea/v

olu

me

mm

2 /mm

3

30 40 50 70 80 90

r = -0.78p < 0.001

Lung Compliance

0

20

40

60

80

100

120

Pressure (cm H2O)

Vol

um

e (m

l) Normal

Lung Compliance

0

20

40

60

80

100

120

Pressure (cm H2O)

Vol

um

e (m

l) Normal

volume

volume

Lung Compliance

0

20

40

60

80

100

120

Pressure (cm H2O)

Vol

um

e (m

l) 73 ml/cm H2O

99 ml/cm H2Op <0.01

Respiratory Muscle Function

inspiration diaphragm external intercostals

MIP - maximal inspiratory pressure MVV - maximal voluntary ventilation

Structural Ventilatory Changes

decreased chest wall compliance increased lung compliance decreased alveolar surface area decreased muscle strength

Lung Volumes

no change TLC increased

FRC RV

decreased VC decreased FEV1

decreased FEV1/FVC

Lung Volumes

0%

20%

40%

60%

80%

100%

young old

IRV

VT

ERV

RV

vital capacity

FRC

Lung Volumes with Age

RV

FRC

TLC

VC

normal aging

0

1000

2000

3000

4000

5000

6000

volu

me

(ml)

PFT Assumptions

FEV1 declines after age 25 men 29 ml/year women 25 ml/year

Cross-sectional vs Longitudinal

-90

-75

-60

-45

-30

-15

0

20 25 30 35 40 45 50 55 60 65 70 75

age years

an

ua

l ch

an

ge

in F

EV 1 m

l

longitudinal

cross sectional

Am J Epidemiology 1990;132:685

Cohort EffectAm J Respir Crit Care Med 1994;149:1218-1226

2300

2500

2700

2900

3100

3300

3500

20 30 40 50 60

Age (years)

FEV

1 (m

illi

lite

rs)

Cohort EffectAm J Respir Crit Care Med 1994;149:1218-1226

2300

2500

2700

2900

3100

3300

3500

20 30 40 50 60

Age (years)

FEV

1 (m

illi

lite

rs)

Cohort EffectAm J Respir Crit Care Med 1994;149:1218-1226

2300

2500

2700

2900

3100

3300

3500

20 30 40 50 60

1959195519511943

1935192919191915

Age (years)

FEV

1 (m

illi

lite

rs)

Source of Variation Aged CohortAm J Respir Crit Care Med 1996;154:S208

0

20

40

60

80

100

0 10 20 30 40 50 60 70 80 90

age years

FE

V1

% a

t a

ge

20 healthy normal

submaximal growth

Gas Exchange

increased dead space increased shunt

base

increased DLCO/VA

An 85 year old has the following room air ABG pH 7.42 Pco2 40

Po2 72 A-a 28

An 85 year old has the following room air ABG pH 7.42 Pco2 40

Po2 72 A-a 28

Is the oxygenation appropriate for age?

An 85 year old with no prior lung disease presents to the ER with sudden onset of dyspnea and pleurtic chest pain and has the following room air ABG pH 7.42 Pco2 40

Po2 72 A-a 28

Is the oxygenation appropriate for age?

Age-Adjusted PO2

PO2 = 104.2 - 0.27(age)

PO2 = 100.1 - 0.325(age)

PO2 = 109 - 0.43(age)

Age-Adjusted PO2

PO2 = 104.2 - 0.27(age) PO2 81

PO2 = 100.1 - 0.325(age) PO2 72

PO2 = 109 - 0.43(age) PO2 75

Age-Adjusted A-a gradient

A-a gradient = 2.5 + 0.21(age)

A-a gradient = 4 + age/4

A-a gradient = 1.4 + 0.43(age)

Age-Adjusted A-a gradient

A-a gradient = 2.5 + 0.21(age) A-a 20

A-a gradient = 4 + age/4 A-a 25

A-a gradient = 1.4 + 0.43(age) A-a 38