Nutrition as a Determinant of Successful Aging: The Quebec Longitudinal Study «NuAge» Pierrette Gaudreau Department of Medicine, University of Montreal

Nutrition as a Determinant of Successful Aging: The Quebec Longitudinal Study «NuAge»

Pierrette GaudreauDepartment of Medicine, University of Montreal

and Centre Hospitalier de l’Université de Montréal Research Center, Angus Technopole, Montreal, Quebec, Canada

andH Payette3, A Khalil3, B Shatenstein1, I Dionne3, M Brochu3, J Morais2, G

Ferland1, T Fulop3, K Gray-Donald2, D Jacques3, MJ Kergoat1, D Tessier3, R Wagner3.

Nutrition and Successful Aging Research Section, Quebec Network for Research on Aging and 1University of Montreal, 2McGill University and 3University of Sherbrooke

Composition:15 co-investigators, 4 Quebec universities2 collaborators from 2 Ontario universities

Expertise: nutrition, geriatrics, biology of aging

(physiology, immunology, cellular and molecular biology, neuroendocrinology), epidemiology, evaluative research, social sciences

Approaches: fundamental, clinical, epidemiological,

evaluative and social

THE TEAM

Management structure:Executive committee: 5 co-principal

investigators (McGill, Montreal and Sherbrooke Universities)

Accountability: General coordination Scientific issues (originality, quality, productivity)Financial integrityEthical issuesMentorship

THE TEAM

PROGRAMMATIC RESEARCH

NuAge sub-studies:

Sarcopenia, voluntary and non-voluntary physical activity

Insulin resistance, sarcopenia and hormonal regulationNutrition and cognitive declineFunctional foods, oxidative stress and

immune/endocrine functionsEating behavior and peripheral peptide levels

regulating appetiteQuality of diet and efficacy of anti-influenza

vaccination Identification of gene markers of successful agingDeterminant of weight loss

95

90

85

80

75

70

2003 2008 2013

Ag

e

SampleRandom sampleQuebec Medicare database, n = 1,793 men/women, Montreal/Sherbrooke

EligibilityGood physical/mental health, Functional autonomy

Follow-upAnnual face-to-face interview,Semi-annual telephone interview

60 502-year-old men and women

60 20 2-year-old men and women

STUDY DESIGN

INCLUSION Community-dwelling men and women 68 to 82 years of age French or English speaking Willing to commit for a 5 year-period Able to walk without help Free of disabilities in activities of daily living No cognitive impairment (3MS > 79) Able to walk 300 m and climb 10 stairs without rest Able to sign an informed consent

EXCLUSION Class II heart failure COPD requiring home oxygen therapy or oral steroids Inflammatory digestive diseases Cancer (radiation therapy, chemotherapy or surgery during

5 previous years)

ELIGIBILITY CRITERIA

RECRUITMENT STRATEGY

Random sample from Quebec Medicare databaseStratification for age and gender (36,183 men/women)

Contacted by mail(18,874)

Phone number No phone number(10,962: 58%) (7,912: 42%)

Telephone contact Telephone contact(8,598: 78%) (735: 9%)

+ 206 Volunteers

Total sample: 1793

Telephone contact(8,598)

Telephone contact(735)

FINAL COHORT AT T1

33% Non eligible 46%

51% Refusal

18%

1322 Recruited

265

COMPUTER-BASED DATA COLLECTION

William softwareTM: 1,000 variables/year/participant

Nutritional: diet, food habits, sensory/physiological functions, anthropometry, body composition

Functional: strength, physical activity, performance

Medical: physical, mental and cognitive health

Social: network, support, participation


Nutritional status determinants General questionnaire: socio-demographic information, socioeconomic resources and income, social network and activities, lifestyle habits, physical health status and disability, medication, health care services access and utilization, eating habits, food-related beliefs and perceptions, hunger and appetite, weight history, osteoporosis risk

Energy and nutrient intakes Life-time food frequency questionnaire Life-time functional food frequency questionnaire Three non-consecutive 24-hour dietary recalls (including 1 during w-end) Nutritional risk assessment questionnaire (Dépistage Nutritionnel des Aînés (DNA©))

Anthropometric indices and body composition estimates Standing height and weight Seated knee height - Triceps, biceps, subscapular and suprailiac skinfold thicknesses Left standing mid-upper-arm, calf, thigh, waist and hip circumferences Fat mass and Fat Free Mass (dual-energy x -ray absorptiometry (DXA))


Muscle strength Maximal voluntary handgrip strength (KPa, Martin Vigorimeter) Maximum isometric strength of the knee extensors and elbow flexors (pound, dynamometer Microfet2TM)

Physical Performance Tests 10 meter walking speed (m/sec) Chair-stands test (time to rise 5 times in sec) Timed Up and Go (TUG) test (chair stand and walking performance) Tinetti balance scale questionnaire (scores 14 items on balance and 10

on gait)

Functional status Nagi score questionnaire (perceived difficulty to carry out 5 daily life tasks) SMAF questionnaire (functional ability in activities of daily living, self-care tasks, instrumental activities of daily living, adaptive tasks, mobility, communication, mental functions) Breslau score (ability to perform walking, bathing, transferring from a bed to a

chair or going to the toilet without help)


Mental health status Cognitive function (Modified Mini-Mental State Examination) Depression (Geriatric Depression Scale)

Health-related quality of life MOS 36-item Short Form Health Survey questionnaire (SF-36) (perceived general health and its consequences on physical, social and emotional functions, life satisfaction)

Physical activity Lifetime total physical activity questionnaire (3 major types of physical

activity throughout life: occupational, household and exercise/sports) Physical Activity Scale for the Elderly (PASE) questionnaire (daily time

for leisure activity, household activity, work-related activity in the past week)

Social activities Social activities questionnaire (social part of the Elderly Activity Inventory questionnaire, 19 types of valued activities)


Follow-up calendar Falls Health events Medication Utilization of health services

Telephone interview (6 months after visit) Falls Health events Medication Utilization of health services 24-hour dietary recall

BIOLOGICAL SAMPLE COLLECTION, BIOLOGICAL SAMPLE COLLECTION, IDENTIFICATION AND MANAGEMENTIDENTIFICATION AND MANAGEMENT

Dedicated computer

Bar code printer

Code 128 is used: alphanumeric symbol of very high density Portable terminal and bar code

reader

Blood: overnight fast (≈50 mL)Saliva: morning and evening (≈2 mL) Urine: fresh morning (≈5 mL)

SCHEME FOR BLOOD PROCESSING

SAMPLES AND PARAMETERS(SERUM)

Blood (serum) Table 1# tubes Volume (uL) Analysis

1 250 Proteins – Free insulin-like growth factor-1

2 250 Proteins – Insulin

3 1000 Proteomics

4 1000 Proteomics

5 1000 Proteomics

6 1000 Proteomics

7 1000 Proteomics

8 250 Proteins – Leptin

9 250 Proteins – Cholecystokinin (CCK)

10 250 Proteins – Ghrelin

11 250 Proteins – Neuropeptide Y (NPY)

12 250 Proteins – Peptide YY 3-36

13 250 Proteins– C-Reactive protein

14 250 Proteins – Tumor necrosis factor alpha (TNF

15 250 Proteins – Interleukin-6



SAMPLES AND PARAMETERS (SERUM)

Blood (serum) Table 118 250 Proteins – Interleukin-10



21 250 Proteins – Interferon gamma

22 250 Proteins – soluble intercellular adhesion molecule-1 (sICAM)

23 250 Proteins – soluble vascular cellular adhesion molecule (sVCAM)

24 500 Metabolic status marker – Free fatty acids

25 400 Cognitive status marker – Vitamin B12 + Folic acid

26 250 Cognitive status marker – Apolipoprotein E

27 250 Steroid hormones – Total testosterone

28 250 Steroid hormones – Total 17--oestradiol total

29 250 Thyroid hormones – Free thyroxine (T4)

30 250 Thyroid hormones – Total thyroxine (T4)

31 500 Steroid hormones – Dehydroepiandrosterone (DHEAS)

32 100 Total antioxidant status (TAS)

33 1000 Future analysis

SAMPLES AND PARAMETERS (PLASMA)

# tubes Vol. (uL) Analysis

1 400Plasma treated with 10% metaphosphoric acid + 0.1 mM

EDTA

2 350Plasma treated with 10% metaphosphoric acid/ 1 mM N-ethyl maleimide + 0.1 mM EDTA

3 250 Oxidative stress marker – Vitamin E

4 200 Oxidative stress marker – malondyaldehyde (lipid damage)

5 250 Oxidative stress marker – F2-isoprostanes (lipid damage)

6 250 Oxidative stress marker – Carbony groups (protein damage)

7 200 Cognitive status marker – Vitamin B6

8 200 Cognitive status marker– Homocysteine


1 150 Oxidative stress marker– Vitamine C

2 100 Oxidative stress marker– GSH


SAMPLES AND PARAMETERS (PLASMA)


1 100 Oxidative stress marker– GSSG




1 400Plasma treated with 10% metaphosphoric acid + 0.1 mM

EDTA

2 350Plasma treated with 10% metaphosphoric acid/ 1 mM N-ethyl maleimide + 0.1 mM EDTA

3 250 Oxidative stress marker – Vitamin E

4 200 Oxidative stress marker – malondyaldehyde (lipid damage)

5 250 Oxidative stress marker – F2-isoprostanes (lipid damage)

6 250 Oxidative stress marker – Carbony groups (protein damage)

7 200 Cognitive status marker – Vitamin B6

8 200 Cognitive status marker– Homocysteine

SCHEME FOR SALIVA AND URINE PROCESSING

SAMPLES AND PARAMETERS (SALIVA, URINE)

# tubes Volume (uL) Saliva analysis

1 1000 Morning cortisol

2 250, 500 or 750 Future analysis

3 1000 Bed time cortisol

4 250, 500 or 750 Future analysis

# tubes Volume (uL) Urine analysis

1 1000 Oxidative stress marker– F2-isoprostanes (lipid damage)

2 1000 Oxidative stress marker– F2-isoprostanes (lipid dmage)

3 1000 Oxidative stress marker– 8-oxo-dGuo (DNA damage)



Life habits

Smoking (%)* 8.88.8 4.9

Alcohol (%<1/month) 84-8984-89 89-97

Socio-demographic

Married (%)* 76 43

Living alone (%)* 18 45

Education (years, X±SD) 11.4±3.9 11.9±5.1

* Age effect

CHARACTERISTICS OF THE COHORT AT T1

Male Female(845) (940)

0102030405060708090

100

Normal Mild Moderate-Severe

Geriatric Depression Scale (GDS)

%

M

F

0 20 40 60 80

Osteoporosis

Thy roïd

Diabetes

Cardiac &

circulatory

Arthritis

Hy pertension

Rep

orte

d di

seas

es

% *P < .01 by age groups

M

F

0

1

2

3

4

5

6

M F

x #

Me

d. P

res

cri

be

d

Age 70

Age 75

Age 80

Mental health Reported diseases

Medication


**

**

**

26.5

27

27.5

28

28.5

29

M F

P = .019 NS

BM

i (kg

/m2 )

Age 70

Age 75

Age 80

0

2

4

6

8

10

12

14

M F

P < .000 P < .000

TUG

(sec

) Age 70

Age 75

Age 80

0

10

20

30

40

50

60

70

80

M F

P < .000 P < .000

Kne

e ex

tens

ion

stre

ngth

(lbs

)

Age 70

Age 75

Age 800

10203040506070

M F M F M F

Low Moderate High

Nutritional risk (ENS©)Male P= .002 Female = NS

%

Age 70

Age 75

Age 80



Meals-On-Wheels (%)* 1.3 1.6

Restaurant (% regularly) 44 42

Prescribed diet (%)* 7 9

3 meals/day (%) >88 >92

Vitamin/mineral supplements

regularly (%) 33 67

winter only (%) 6 6

occasionally/never (%) 61 27

* Age effect

FOOD BEHAVIOR AT T1


Nutrition-related

Problem with Taste (%) 5.2 6.8Smell (%)* 13.5 9.6Swallowing (%)* 9.0 14.1Chewing (%)* 4.3 6.7

Appetite (score>5/10) 68 71

Food habits (% change) 33 39

Quantity of food (% change) 34 39

Food excluded (%) 36 44

* Age effect


Characteristics Associated with Dietary Intakes

Energy Protein

F 0.17* (P=0.003) 0.16 (P=0.005)

AppetiteAppetite (1-10)M 0.21 (P=0.001) 0.26 (P<0.000)

* Pearson correlation (r) 2-tailed

NOT associated :life habits, socio-demographic, physiological problems, food habits and behaviors


PRELIMINARY RESULTS IN A SUB-GROUP OF 360 PARTICIPANTS AT T1

Objectives:1. To measure serum levels of markers influencing muscle

strength, anthropometric indices and/or dietary intakes (serum free IGF-1, insulin, glucose)

2. To assess muscle strength

3. To assess anthropometric indices

4. To examine dietary intakes

SERUM FREE IGF-1, INSULIN AND GLUCOSE LEVELS AT T1: TRANSVERSAL DATA

0102030405060708090

100

Insulin (pmol/L)

70 years 75 years 80 years

Men

Women

0

0,10,2

0,30,4

0,50,6

0,70,8

Free IGF-1 (ng/mL)


Men

Women

5

5,1

5,2

5,3

5,4

5,5

5,6

5,7

5,8

Glucose (mmol/L)


Men

Women

Women: P< 0.05, one-way ANOVA


MUSCLE STRENGTH AT T1: TRANSVERSAL DATA

0

20

40

60

80

100

Rig

ht

Gri

p S

tre

ng

th (

KP

a)


Men

Women

0

20

40

60

80

Rig

ht

Bic

ep

S

tre

ng

th (

Po

un

d)


Men

Women

0

20

40

60

80

100

Rig

ht

Qu

ad

ric

ep

S

tre

ng

th (

Po

un

d)


Men

Women


***

Men: P< 0.0001, one-way ANOVA



******



****

ANTHROPOMETRIC INDICES AT T1: TRANSVERSAL DATA

0102030405060708090

Measured BW (kg)


Men

Women

1,45

1,5

1,55

1,6

1,65

1,7

Measured height (m)


Men

Women

80

85

90

95

100

105

Waist circum-ference (cm)


Men

Women


*

MACRONUTRIENTS AND ENERGY INTAKES AT T1: TRANSVERSAL DATA

0102030405060708090

Protein intake (g/day)


Men

Women

0

10

20

30

40

50

60

70

80

Total lipid intake (d/day)


Men

Women

170

180

190

200

210

220

230

240

Glucid intake (g/day)


Men

Women

0

500

1000

1500

2000

2500

Energy intake

(Kcal/day)


Men

Women


*

VITAMIN C INTAKE AT T1: TRANSVERSAL DATA

0

20

40

60

80

100

120

140

Vitamin C (mg/day)


Men

Women

PRELIMINARY RESULTS IN A SUB-GROUP OF 103 PARTICIPANTS AT T1

Objectives:

1. To examine the relationship between serum/plasma markers of oxidative stress defenses (TAS, vitamin C and vitamin E) and consumption of antioxidant-rich food (ARF)

2. To be done… To determine the beneficial effects of consuming ARF, related to regulation of OS, on the maintenance of immune and endocrine status and general health

LIFETIME CONSUMPTION OF ANTIOXIDANT-RICH FOODS

Shatenstein B et al. 2003 An approach for evaluating lifelong intakes of functional foods in elderly people. J Nutr 133:2384

CHARACTERISTICS OF THE QUESTIONNAIRE

Non quantitative questionnaire

Categorization of frequency of consumption Never or rarely (few times/year) Often (several times/month) Regularly (everyday)

Evaluation of present and past consumption at 65, 45, 25 and 10 years of age

Fiability: 73%

27 foods (fruits, vegetables, corn cereal, nuts, cacao-containing products, green tea, red wine)

Exemple de substances antioxydantes présentes aliments fonctionnels

Family Class Example ________________________________________________________Phytochemicals

Polyphenols Flavonoids Blueberry, red winePhenolic acids green tea, dark

chocolate

Terpenes Carotenoids Carrot, tomato

Sulfur compounds Allyl sulfide GarlicIsothiocyanates Brussels sprouts,

broccoli

Vitamins Vitamin E Nuts(alpha et gamma tocopherol) Vitamin C Citrus fruits

FAMILIES AND CLASSES OF ANTIOXIDANT-RICH FOODS

STUDY POPULATION: FIRST 103 MEN AND WOMEN ENROLLED

Age group (years) Men (%) Women (%)

70 2 27 45

75 2 43 35

80 2 30 20

CORRELATION BETWEEN DAILY PRESENTAND PAST CONSUMPTION OF 27 ARF

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

Pea

rso

n c

orr

elat

ion

(r)

men women

65 years

45 years

25 years

10 years

**

*

*P <0.001

*

**

Reported consumption of ARFF at T1 is strongly correlated with that reported for the ages of 65, 45, 25, and 10 years

DETECTION OF TAS AND VITAMINS C AND E

Total antioxidant statut (TAS) Spectrophotometric analysis of serum capacity to inhibit

2,2’- azinobis (3-ethylbenzothiazoline-6-sulfonate) (ABTS) formation (ABTS) en the presence de H2O2 and metmyoglobin

Percentage of inhibition corresponds to TAS value expressed in Trolox (vitamin E analog) equivalent

Vitamin E Plasma, hexane/methanol extraction, HPLC/coulometric electrochemical detection

Vitamin CPlasma, HPLC/coulometric electrochemical detection

Résumé

Positive and significant correlation (Pearson r) between current consumption frequency of ARF and TAS (P = 0.026)

Significant correlation between the sum of 27 ARF eaten currently and daily and circulating TAS and vitamin C (modulated by gender)

No correlation with vitamin E No association between TAS and vitamin C levels Dietary supplements (vitamins A, C, E and/or selenium) did not significantly

affect TAS and, vitamin C levels or modify the relationship between TAS, vitamin C and current daily consumption of ARF

0 1 2 3 4 5 6 7 8 9 10

Nbre d'AFRAO /jour

30,00

40,00

50,00

60,00

Vit

am

ine

C

Men

Women

p = 0,002 R Square = 0,139

Y = 28,997 + 2,225 X + 12,749 SEXE

SERUM TAS AND PLASMA VITAMIN C LEVELS IN MEN AND WOMEN AT T1: TRANSVERSAL DATA

Unique initiative in research on aging and nutrition Efficacy of the various procedures Preliminary results (T1) indicate promising research avenues

(serum free IGF-1 levels,

AFR consumption and serum/plasma TAS and vitamin C) A gold mine of data and biospecimens Importance to conduct targeted sub-studies

Development Nutrition health promotion programs Disease prevention strategies Guidelines for optimal nutrition Evidence-based data for health care policy makers Food products

CONCLUSION AND PERSPECTIVE

Research personnel Coordinators Dieticians, nurses, laboratory technicians Secretaries

Collaborators Members of the Nutrition and Successful Aging Research Section, Quebec Network for Research on Aging

1,793 kind women and men

ACKNOWLEDGEMENTSACKNOWLEDGEMENTS

Documents

Nutrition as a Determinant of Successful Aging: The Quebec Longitudinal Study «NuAge» Pierrette Gaudreau Department of Medicine, University of Montreal