Plasma amino acid concentrations elderly men and women1’2 Benjamin

Caballero,

ABSTRACT large

neutral

Ray

E Gleason,

Postabsorptive

plasma

amino

acids

(age 7 1 ± 8 y) and Plasma concentrations

(LNAAs)

and

Richard

measured

in young

gender-related jects because

difference was not observed among aging was associated with a significant

in females

vealed

but

amino

leucine,

tryptophan

amino

acid

consisting

than

in males.

positive

in young

from effect

of age and

methionine.

Tryptophan

a significant

response

of a 14%

decline

ranges are presented for for each of the amino

in the

young acids.

tyrosine

subjects.

elderly

Am

re-

not

suits the

only

in those

were

Percentile

anti-inflammatory

drugs.

did not differ not receiving

significantly from these medications.

and males Nutr 199 l;53:

Venous Plasma

WORDS

amino

acids,

aging,

normal

early were

values

range

concentrations are not tightly

in response

to food

( 1-4).

tered

in liver

(8),

in response

amino

phtalaldehyde cate

plasma

consumption

acid

containing

and

Plasma

amino

renal

disease

(5,

(9,

10),

and

acid

to stress

mixtures

acid

or amino

consequent

hormone

concentrations

are

in diabetes

6),

and

after

(7),

also

A sample

al-

food

of

by the

additives

,

nonexercising

normal

subjects

Significant

differences of several

amino

acids

in young

Similarly,

data

from

small

(13).

dividuals

suggest

that

the

described

are

centration males

were

ofplasma age

between

age-related

the adult

numbers decline

and

mabity.

gender.

subjects and way analysis

plasma males

conand

of elderly

in insulin

may cause an elevation in the plasma branched-chain acid concentration via a mechanism similar to that

served

in obese

subjects

Characterization is important preting

from

normal and

dietary

ranges

young

LNAA subjects

Am J C/in NuIr

concentrations of both

for plasma

diagnostic and

observed

amino

and

purposes

metabolic

changes from a baseline plasma amino The present study describes age- and in plasma

Software,

determined

system (model postcolumn o-

detection. with

Dupli-

5% sulfosalicylic

was included

Dewey

standard.

in each

run as

across the study fluorimetrically

(18).

by using

means

significance

Cambridge,

tubes samples Plasma

Levene’s

between

test of nor-

young

and

performed range

of differences

between

elderly by twotest was groups.

quartile ranges were calculated for each was done in the CLINFO system (BBN

MA)

and

statistical

analysis

used

the SAS

ob-

(14-17).

ofthe for clinical

results

to determine

age and gender

were

between females and males were of variance. Tukey’s studentized

used

respon-

siveness amino

ofgroup

Confidence intervals and group. Data management

concentrations

of variability was determined

and

group

nonsteroid

as an internal

plasma

was examined

fe-

or

same

fluorimetric

norleucine/L

of Denckla

in-

receiving

elderly

in heparin-treated

deproteinized

human

Comparisons

disease; preceding

was

LNAA

ofthe

tryptophan)

control. Coefficient Plasma tryptophan

LNAAs

none in the drugs,

obtained

and

were

cell count

2 mo

columns in an HPLC Carlsbad, CA), with

120 imol

method

un-

an overnight fast. Plasma at -30 #{176}C until analysis.

derivatization

Data distribution

the

and

plasma

(excluding

of pooled

55

All subjects

or metabolic

subjects

those

were after frozen

samples

an interassay was < 6%.

in obesity

administration

acid-containing

to normal individuals ( 1 1 12). Two important physiological determinants in fasting,

samples

concentrations

of the large neutral amino acids regulated and can fluctuate over a wide

living,

Their

by using cation-exchange 334, Beckman Instruments,

Introduction

secretion

blood

liver,

antihypertensive

in the morning, centrifuged and

LNAA

Plasma (LNAAs)

free

in males,

aged

(age

(complete

5% during

Twelve

digitalis,

tests

ofkidney,

were

138).

=

subjects

elderly

blood urea nitrogen concentracriteria included abnormal re-

of

or formulas.

receiving

groups:

blood

weight

All subjects

diets

two

40 y, n

(age

a history

tests;

of 2 12 adult

into

examination,

in body

study.

1249-52.

KEY

consisted

divided

young

a physical

special

females

J C/in

and

or changes

on

the

to age

elderly

and

but

were

and hemoglobin, glucose, and tions), and urinalysis. Exclusion

valine,

was

74)

=

derwent

analysis

subjects

studied

y. They

y, n

This

on plasma

phenylalanine,

methods

population

20-90

elderly subrise in plasma

female

or

to exhibit

males.

Multiple-regression

concentrations

and

isoleucine,

plasma

not

acid

a significant

females

and

The

1 38 young (age 26 ± 5 y) healthy subjects. of valine, leucine, and isoleucine were

lower

LNAAs

Subjects

of the in 74 elderly

significantly

of plasma

J Wuriman

concentrations

were

in healthy

experiments

acid profile gender-related in healthy

acids

I From the Clinical Research Center, Massachusetts Institute of Technology, Cambridge. 2 Address reprint requests to B Caballero, Center for Human Nutrition,

for interin which

are expected. differences elderly

The Johns 21205.

and

sexes.

l99l;53:1249-52.

Printed

in USA.

© 1991 American

Downloaded from https://academic.oup.com/ajcn/article-abstract/53/5/1249/4731877 by Denise Hannibal user on 11 April 2018

Society

Hopkins

University,

Received

August

Accepted

for publication

for Clinical

615 North

Wolfe

Street,

Baltimore,

MD

8, 1990.

Nutrition

October

31, 1990. 1249

CABALLERO

1250

(SAS

Institute,

Angeles)

Cary,

software

The

relative

LNAA

NC)

influences

analysis

BMDP

of age

concentrations

sion

and

(BMDP

were

with

and

body

explored

standardized

weight

by using

regression

advantage

affected model This

of this

approach

is that

by the scale or range because the regression is particularly

The

obesity

index

was

uals

ofthe

Life

Insurance

body

corresponding tables

are

from

such

actual

body

Mean

1.

Young

Metropolitan

elderly

no significant crease The

groups

group.

Within

differences

female

groups.

each

between

The

the

obesity

index

age

group,

mean

ages

showed

with age in both males and females. median and range values for the 5th,

percentiles presented plasma those

of all measured in Table

amino

celing

the

acids

correlation

amino

age acids

concentrations tyrosine (but

significant

of beucine, not tryptophan

At the

50th

for the

branched-chain

231 231

267 263

294 291

90 81

120 95

142 109

156 120

218 150

75 80

126 110

140 133

157 148

190 180

45 39

62 48

71 54

84 63

111 80

42 37

64 53

74 68

81 77

108 110

41 38

53 48

58 54

65 58

78 72

42 35

55 50

61 58

66 64

95 108

38 31

54 47

61 52

70 61

87 72

35 40

55 50

63 59

69 75

90 88

46 37

56 46

63 52

68 59

80 69

46 37

52 46

54 52

59 59

72 69

318 273

399 318

450 347

508 394

630 506

289 292

420 370

455 442

492 473

580 545

group

percentile

with

acids

for the

Age(y) Weight

68)

=

were

22-24%

7-b 3% higher group.

In males

26±4 (kg)

70.5

BMIt OI

24.5 1.06

(n

92b

72.4 26.2 1.12

25±5’

± 10.3’ ± 2.5 ± 0.12

Male Female

only

Elderly

(n

=

42)

7l±l’

61.4

±

26.1 1.05

± 3.1 ± 0.14

± ± ±

9.3’ 2.1 0.1

62.4 28.1 1.16

± 8.6k’ ± 3.0 ± 0.14

Discussion These are

g ± SEM. Groups

< 0.05

(Tukey’s

with

different

studentized-range

superscript test).

letters

t Body mass index, expressed as weight (kg)/[height f Obesity index, expressed as actual weight/desirable weight

from

group

Male Female All branched chain Young group Male Female Elderly group Male Female

Female

32)

=

goup

for phethe

group

T

higher

in plasma

Male

72)

Male Elderly

a

=

Young group Female

Elderly group

(n

Tyrosine

of all

phenylalanine, and for female subjects.

Female

Male

Female

positive

coefficients

Young group

(n

can-

on the plasma

and

studied

Elderly group Male

of subjects.

group

Feale

< 0.0001).

age-related difference was a 14% reduction concentrations in the elderly subjects.

of the groups

elderly

Young

than

standardized

and

Female Phenylalanine

are

effects ofage

concentrations

Male

lower

females,

nybalanine

TABLE 1 Characteristics

tyrosine

(P

isoleucine, valine, or methionine) amino

95th

concentration

tryptophan

positive

these

and

for young

Elderly group

in-

group

a significant

plasma

Female

of the male

age

significant tryptophan

body

211 201

Isoleucine Young group Male

were

significantly

observed

the

except

there

75th,

in elderly

exhibited

analysis

3) revealed

25th,

exhibited

sexes and

in Table and 72

beucine, and isoleucine groups. The concentration

group

Multiple-regression

(Table

P

154 174

Male

a significant

in each

significantly

between

between

measured

females

increased

the female

acids

of valine, three

other

difference

In addition,

amino

2. Young

concentrations found in the

these

a

338 289

Female Elderly group Male

studied are presented age was 25 ± 5 y in the young group

(± SEM)

± 8 y in the

and

265 212

Leucine

(20).

ofthe

95

238 192

Female characteristics

75

210 171

Male

Results The

50

and sex

172 144

Female Elderly group

individ-

1959

25

by age group

imo//L

Female the

acid concentrations 5

not

variables

the

amino

Val

acids.

for medium-frame

sex, taken

of plasma

Stan-

variables in the in SD units (19).

by dividing

weight

2

Aminoacid

when all variables and unit variance.

comparing

amino

calculated

by the desirable

plasma

the comparisons

when

and the individual

on

AL

TABLE Pentiles

multiple-regres-

of the different coefficients are

important

as age, weight, weight

Los

coefficients.

dardized coefficients are estimates obtained in the model are standardized to zero mean The

Software,

packages.

ET

are significantly (m)J2. body

weight.

different,

(Desirable

ref2o.)

Downloaded from https://academic.oup.com/ajcn/article-abstract/53/5/1249/4731877 by Denise Hannibal user on 11 April 2018

data

show

significantly

Further,

the data

that

lower

indicate

fasting in young

that

plasma women

those

LNAA than

concentrations in young

concentrations

icantly with age in women but not in men. Thus, differences in plasma amino acid concentrations young subjects disappear in the elderly population.

men.

rise signifthe

sex-related observed in Elderly men,

PLASMA TABLE 3 Effects of aging females*

AMINO

ACIDS

IN

concentrations on plasma

Dependent

amino

acid concentrations

in males

Standardized coefficient

variable

and

were

P

in elderly

observed

0.7089 0.0001

affected

consequence amino acid

the significant concentrations

0.1149 0.3328

0.2746 0.0003

decrease

0.1676 0.0008

-0.2864 -0.0222

the

insulin

acids

such

from

the

a Multiple-regression

analysis

with

age

as the

could

explain

0.0050 0.8129

tutionalized.

independent

the

on the

other

hand,

Plasma

acids

many

studies

pooled

sex-related

notably

chain

amino

LNAA

found

acids, factors

could

have

higher

lower

the

phenylalanine, play

acids,

uremia

(6).

possibility could

The

decline

concentration

ofthe association

composition.

would

of branched-chain

amino

Our

a marked

study

found

acids

females glucose during tend to

study

a figure very similar decline in tryptophan.

tryptophan

concentrations

individuals

(8, 29).

was

The

noninsti-

y found

out

intake

by the

in the

sig-

valine, with authors,

population

concentrations with

in elderly

earlier

reports.

to our own finding A similar decline found

opposite

In a mean con-

of a 14% in plasma

in insulin-resistant

age-related

obese

changes

in plasma

amino acids causes a significant ratio, which correlates with

availability mood

(30). Whether and behavior

this decrease affects in elderly people re-

to be explored.

In summary, LNAA

our

study

concentrations women.

should mentally

provided

normative

in healthy,

The

gender-

and

of elderly

by Josie

Core

data

well-nourished age-related

be considered when evaluating induced changes in plasma

in groups

Center

65-85

Fukagawa et al (16) reported that was 14.7% lower than in young

tryptophan and branched-chain decline in the tryptophan-LNAA

analysis

and

is consistent

trol subjects, age-related

and

it

amino

and

aged

as pointed

tryptophan

elderly men, concentrations

We acknowledge

possible

lower

in our

is

in females,

out.

in plasma

found

factors)

con-

ofthe amino acids threonine compared

protein

be ruled

plasma sensitivity

on

plasma

elderly

differences

men

reported

physiological or experiamino acid concentrations

people.

U

the excellent Sabio

and

Marie

technical Marcucci

support ofthe

for the amino MIT

Clinical

acid

Research

Laboratory.

References

most-insulin-responsive acids,

as described

affecting We

a lower

in females rise

and

plasma

than do men output could

amino

favor

One Young

output

between

branched-chain

females.

the lower

to males.

possibly

correlations

Simi-

branched-

in young

sensitivity.

amino

factor

is body

(1 3, 22).

not

responsiveness

in their

well-nourished

but,

group ofsix tryptophan

in pread-

ofthe

tyrosine

of the

branched-chain

significant

levels

insulin insulin

concentrations

concentrations

females

insulin

per unit of plasma (23). Such increased the

and

(28)

cleared

in branched-chain

in 2 1 men

of a marginal

studied

mains

amino

were

study

subjects

brain tryptophan serotonin-dependent

differences

in plasma

lower

relative

in insulin

plasma signif-

studies

a role in determining

in females

Another

gender-related

and

but or did

concentrations

differences

males

glucose-mediated

amino

Such

relevant before,

of branched-chain

because

significantly

may

plasma

reported

2).

subjects

LNAA

These

major

be differences

disposal rate clamp studies

mass.

no

concentrations

factor

21).

between

study

Several

female

concentration

adolescence,

found

concentrations our

and

tryp-

(Table

reported

in plasma

(13,

after

children

larly,

been

for male

a lower

in females

to develop

olescent

values

in plasma

group

of the physiologically have

differences

most

acids

appear

adults

young

a separate elderly group. Studies comparing concentrations in men and women reported

for adults, amino

decline

to the

of most

in healthy

not include amino acid icant

a consistent

relative

concentrations

amino

acid

exhibit

concentration

A recent

control

males

tophan

women. in our study

it

(26).

are

in insulin

rise

a

that

obesity

which

rise

by other

larger

hy-

se causes

in a dose-dependent

decrease

the

> 200%

with

(1 7) and

in insulin

a progressive

lower plasma concentrations isoleucine, phenylalanine,

young

increased in a group

per

with

action

(or enhanced

acids in elderly All subjects

variable

insulin

biological

in part

aging

chain,

as a

in plasma disappeared

acids

associated

decrease

cause

If this

0.9647 0.0085

and

reported

people

branched

age-related

conceivably pronounced

and BMI as a fixed factor. Standardized regression coefficients adjust all variables to zero mean and unit variance, and they represent change in the dependent variable (in SD units), relative to changes ofthe independent variable (in SD units).

resistance under

the

that

in normal

as the

circulation

more

also amino

known

sensitivity

amino

centrations.

increase

tryptophan,

but the group included people with which in itself may be associated

For

nificantly leucine,

et al (15)

branched-chain

potentiates

could

for

changes

age-related

sex-related differences found in young subjects

It is well

(27),

no significant

3). This except

Galante

in insulin

fashion

0.0046 0.2519

subjects.

concentrations

perarninoacidemia.

0.9262 0.0001

0.1475 0.308 1

all LNAAs

of elderly women, ideal body weight,

0.0098 0.4604

whereas

males(Table

in females

plasma -0.0392 0.3636

females

in elderly

in the elderly Valine Males Females Leucine Males Females Isoleucine Males Females Phenylalanine Males Females Tyrosine Males Females Tryptophan Males Females

1251

AGING

in the

plasma

(24)

and

the

summed

acids plasma relative plasma

for LNAA

others

and

(25) plasma

lean

body

concentration to males. amino

acid

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5. Fernstrom

ET

adults,

differences normal

and

1 19-26.

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30.

Fernstrom regulation

4 14-6.

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in