Nutrition as a Determinant of
Successful Aging: The Quebec
Longitudinal Study «NuAge»
Pierrette Gaudreau
Department of Medicine, University of Montreal
and Centre Hospitalier de l’Université de Montréal Research Center,
Angus Technopole, Montreal, Quebec, Canada
and
H 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
THE
TEAM
Composition:
15 co-investigators, 4 Quebec universities
2 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 integrity
Ethical issues
Mentorship
PROGRAMMATIC RESEARCH
NuAge sub-studies:
 Sarcopenia, voluntary and non-voluntary physical
activity
 Insulin resistance, sarcopenia and hormonal regulation
 Nutrition and cognitive decline
 Functional foods, oxidative stress and
immune/endocrine functions
 Eating behavior and peripheral peptide levels
regulating appetite
 Quality of diet and efficacy of anti-influenza
vaccination
 Identification of gene markers of successful aging
 Determinant of weight loss
STUDY DESIGN
 Eligibility
Good physical/mental
health,
Functional autonomy
Age
 Sample
Random sample
Quebec Medicare
database,
n = 1,793 men/women,
Montreal/Sherbrooke
 Follow-up
Annual face-to-face
interview,
Semi-annual telephone
interview
95
60 20 2-year-old
men and women
60 502-year-old
men and women
90
85
80
75
70
2003
2008
2013
ELIGIBILITY CRITERIA
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)
RECRUITMENT STRATEGY
Random sample from Quebec Medicare database
Stratification for age and gender (36,183 men/women)
Contacted by mail
(18,874)
Phone number
(10,962: 58%)
No phone number
(7,912: 42%)
Telephone contact
(8,598: 78%)
Telephone contact
(735: 9%)
FINAL COHORT AT T1
Telephone contact
(8,598)
33%
51%
1322
Telephone contact
(735)
Non eligible
Refusal
Recruited
+ 206 Volunteers
Total sample: 1793
46%
18%
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
COMPUTER-BASED DATA COLLECTION
 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))
COMPUTER-BASED DATA
COLLECTION
 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)
COMPUTER-BASED DATA
COLLECTION
 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)
COMPUTER-BASED DATA
COLLECTION
 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,
IDENTIFICATION AND MANAGEMENT
Blood: overnight fast (≈50 mL)
Saliva: morning and evening (≈2 mL)
Urine: fresh morning (≈5 mL)
Bar code printer
Dedicated computer
Code 128 is used: alphanumeric
symbol of very high density
Portable terminal and bar code
reader
SCHEME FOR BLOOD PROCESSING
SAMPLES AND PARAMETERS
(SERUM)
# tubes
1
Volume (uL) Analysis
Blood
(serum)
Table 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 a)
15
250
Proteins – Interleukin-6
16
250
Proteins – Interleukin-2
17
250
Proteins – Interleukin-4
SAMPLES AND PARAMETERS
(SERUM)
250
Proteins – Interleukin-10
20
250
Proteins – Interleukin-15
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-b-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
18
19
Blood
(serum)
Table 1
250
Proteins – Interleukin-12
SAMPLES AND PARAMETERS
(PLASMA)
# tubes
Vol. (uL)
Analysis
1
400
Plasma treated with 10% metaphosphoric acid + 0.1 mM EDTA
2
350
Plasma 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
# tubes
Vol. (uL)
Analysis
1
150
Oxidative stress marker– Vitamine C
2
100
Oxidative stress marker– GSH
3
150
Future analysis
SAMPLES AND PARAMETERS
(PLASMA)
# tubes
Vol. (uL)
Analysis
1
400
Plasma treated with 10% metaphosphoric acid + 0.1 mM EDTA
2
350
Plasma 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
# tubes
Vol. (uL)
Analysis
1
100
Oxidative stress marker– GSSG
2
150
Future analysis
3
100
Future analysis
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)
4
1000
Oxidative stress marker– 8-oxo-dGuo (DNA damage)
5
1000
Oxidative stress marker– 8-oxo-dGuo (DNA damage)
CHARACTERISTICS OF THE
COHORT AT T1
Male
(845)
Female
(940)
Life habits
Smoking (%)*
8.8
4.9
Alcohol (%<1/month)
84-89
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
Reported diseases
100
90
80
70
60
50
40
30
20
10
0
**
Reported diseases
Hy pertension
M
F
Arthritis
*
Cardiac &
*
circulatory
Normal
Mild
M
F
Diabetes
*
Thy roïd
*
Osteoporosis
ModerateSevere
0
20
40
60
%
Geriatric Depression Scale (GDS)
*P < .01 by age groups
Medication
6
x # Med. Prescribed
%
Mental health
5
4
Age 70
3
Age 75
Age 80
2
1
0
M
F
80
CHARACTERISTICS OF THE
COHORT AT T1
29
14
12
Age 70
28
Age 75
27.5
Age 80
TUG (sec)
2
BMi (kg/m )
28.5
27
Age 70
8
Age 75
6
Age 80
4
2
26.5
0
M
F
M
F
P = .019
NS
P < .000
P < .000
80
70
60
50
Age 70
40
Age 75
30
Age 80
20
%
Knee extension strength (lbs)
10
70
60
50
40
30
20
10
0
Age 70
Age 75
Age 80
M
10
0
F
Low
M
F
P < .000
P < .000
M
F
M
Moderate
Nutritional risk (ENS©)
Male P= .002
Female = NS
F
High
FOOD BEHAVIOR AT T1
Male
(845)
Female
(940)
Meals-On-Wheels (%)*
1.3
1.6
Restaurant (% regularly)
44
42
Prescribed diet (%)*
7
9
3 meals/day (%)
>88
>92
regularly (%)
winter only (%)
33
6
67
6
occasionally/never (%)
61
27
Vitamin/mineral supplements
* Age effect
CHARACTERISTICS OF THE
COHORT AT T1
Nutrition-related
Male
(845)
Female
(940)
Problem with
Taste (%)
Smell (%)*
Swallowing (%)*
Chewing (%)*
5.2
13.5
9.0
4.3
6.8
9.6
14.1
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 OF THE
COHORT AT T1
Characteristics Associated with Dietary Intakes
Energy
Protein
F
0.17* (P=0.003)
0.16 (P=0.005)
M
0.21 (P=0.001)
0.26 (P<0.000)
Appetite (1-10)
* Pearson correlation (r) 2-tailed
NOT associated :
life habits, socio-demographic, physiological problems, food habits and behaviors
PRELIMINARY RESULTS IN A SUBGROUP 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
Women: P< 0.05, one-way ANOVA
Women: P< 0.05, one-way ANOVA
0,8
0,7
0,6
0,5
Free IGF-1
0,4
(ng/mL)
0,3
0,2
0,1
0
100
90
80
70
Insulin 60
50
(pmol/L) 40
30
20
10
0
Men
Women
70 years
75 years
80 years
Men
Women
5,8
70 years
75 years
80 years
5,7
5,6
5,5
Glucose
5,4
(mmol/L)
Men
Women
5,3
5,2
5,1
5
70 years
75 years
80 years
MUSCLE STRENGTH AT T1:
TRANSVERSAL DATA
Men: P< 0.0001, one-way ANOVA
Right Bicep
Strength (Pound)
Women: P< 0.0001, one-way ANOVA
Men: P< 0.0001, one-way ANOVA
***
100
60
Men
40
Women
20
0
70 years
80
60
Men
Women
40
20
75 years
80 years
Men: P< 0.001, one-way ANOVA
Women: P< 0.05, one-way ANOVA
0
70 years
75 years
80 years
Right Quadricep
Strength (Pound)
Right Grip Strength (KPa)
Women: P< 0.001, one-way ANOVA
***
***
80
100
80
*
***
60
Men
40
Women
20
0
70 years
75 years
80 years
ANTHROPOMETRIC INDICES AT T1:
TRANSVERSAL DATA
1,7
1,65
Measured 1,6
height (m) 1,55
Men: P< 0.01, one-way ANOVA
Women
1,5
*
90
80
70
60
Measured 50
BW (kg) 40
30
20
10
0
Men
1,45
70 years
75 years
80 years
Men
Women
70 years
75 years
80 years
105
100
95
Waist circumference (cm) 90
Men
Women
85
80
70 years
75 years
80 years
MACRONUTRIENTS AND ENERGY INTAKES
AT T1: TRANSVERSAL DATA
80
90
80
70
60
Protein intake 50
40
(g/day)
30
20
10
0
70
60
Men
Women
Total lipid 50
intake 40
(d/day) 30
Men
Women
20
10
70 years
75 years
0
80 years
70 years
75 years
80 years
Men: P< 0.05, one-way ANOVA
*
2500
240
230
2000
220
Glucid intake 210
(g/day)
200
Men
Women
190
Energy 1500
intake
(Kcal/day) 1000
Men
Women
500
180
170
70 years
75 years
80 years
0
70 years
75 years
80 years
VITAMIN C INTAKE AT T1: TRANSVERSAL DATA
140
120
100
Vitamin C 80
(mg/day) 60
Men
Women
40
20
0
70 years
75 years
80 years
PRELIMINARY RESULTS IN A SUBGROUP 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, cacaocontaining products, green tea, red wine)
Exemple
antioxydantes
FAMILIESde
ANDsubstances
CLASSES OF ANTIOXIDANT-RICH
FOODS fonctionnels
présentes aliments
Family
Class
Example
________________________________________________________
Phytochemicals
Polyphenols
Flavonoids
Phenolic acids
Blueberry, red wine
green tea, dark
chocolate
Terpenes
Carotenoids
Carrot, tomato
Sulfur compounds
Allyl sulfide
Isothiocyanates
Garlic
Brussels sprouts,
broccoli
Vitamins
Vitamin E
(alpha et gamma tocopherol)
Vitamin C
Nuts
Citrus fruits
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 PRESENT
AND PAST CONSUMPTION OF 27 ARF
0,9
Pearson correlation (r)
0,8
*
*
*
0,7
0,6
0,5
*
*
0,4
0,3
*
65 years
45 years
25 years
10 years
0,2
0,1
0
men
women
*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 C
Plasma, HPLC/coulometric electrochemical detection
Résumé
SERUM TAS AND PLASMA VITAMIN C LEVELS IN
MEN AND WOMEN AT T1: TRANSVERSAL DATA
 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
CONCLUSION AND PERSPECTIVE
 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
ACKNOWLEDGEMENTS
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