Abstract
Background: Age-related changes in biological processes such as physiological dysregulation (the progressive loss of homeostatic capacity) vary considerably among older adults and may influence health profiles in late life. These differences could be related, at least in part, to the impact of intrinsic and extrinsic factors such as sex and physical activity level (PAL). Objectives: The objectives of this study were (1) to assess the magnitude and rate of changes in physiologi-cal dysregulation in men and women according to PAL and (2) to determine whether/how sex and PAL mediate the apparent influence of physiological dysregulation on health outcomes (frailty and mortality). Methods: We used data on 1,754 community-dwelling older adults (age = 74.4 ± 4.2 years; women = 52.4%) of the Quebec NuAge cohort study. Physiological dysregulation was calculated based on Mahalanobis distance of 31 biomarkers regrouped into 5 systems: oxygen transport, liver/kidney function, leukopoiesis, micronutrients, and lipids. Results: As expected, mean physiological dysregulation significantly increased with age while PAL decreased. For the same age and PAL, men showed higher levels of physiological dysregulation globally in 3 systems: oxygen transport, liver/kidney function, and leukopoiesis. Men also showed faster global physiological dysregulation in the liver/kidney and leukopoiesis systems. Overall, high PAL was associated with lower level and slower rate of change of physiological dysregulation. Finally, while mortality and frailty risk significantly increased with physiological dysregulation, there was no evidence for differences in these effects between sexes and PAL. Conclusion: Our results showed that both sex and PAL have a significant effect on physiological dysregulation levels and rates of change. Also, although a higher PAL was associated with lower level and slower rate of change of physiological dysregulation, there was no evidence that PAL attenuates the effect of physiological dysregulation on subsequent declines in health at the end of life. Substantial work remains to understand how modifiable behaviors impact the relationship between physiological dysregulation, frailty, and mortality in men and women.
References
1.
Case
A
, Paxson
C
. Sex differences in morbidity and mortality
. Demography
. 2005
;42
(2
):189
–214
. .2.
Fried
LP
, Tangen
CM
, Walston
J
, Newman
AB
, Hirsch
C
, Gottdiener
J
, Frailty in older adults: evidence for a phenotype
. J Gerontol A Biol Sci Med Sci
. 2001
;56
(3
):M146
–56
. .3.
Gordon
EH
, Peel
NM
, Hubbard
RE
. The male-female health-survival paradox in hospitalised older adults
. Maturitas
. 2018
;107
:13
–8
. .4.
Gordon
EH
, Peel
NM
, Samanta
M
, Theou
O
, Howlett
SE
, Hubbard
RE
. Sex differences in frailty: a systematic review and meta-analysis
. Exp Gerontol
. 2017
;89
:30
–40
. .5.
Corrao
S
, Argano
C
, Natoli
G
, Nobili
A
, Corazza
GR
, Mannucci
PM
, Sex-differences in the pattern of comorbidities, functional independence, and mortality in elderly inpatients: evidence from the RePoSI register
. J Clin Med
. 2019
;8
(1
):81
. .6.
Crimmins
EM
, Kim
JK
, Solé-Auró
A
. Gender differences in health: results from SHARE, ELSA and HRS
. Eur J Public Health
. 2011
;21
(1
):81
–91
. .7.
Murphy
SL
, Kochanek
KD
, Xu
J
, Heron
M
. Deaths: final data for 2012
. Natl Vital Stat Rep
. 2015
;63
(9
):1
–117
.8.
Tidiere
M
, Gaillard
JM
, Müller
DW
, Lackey
LB
, Gimenez
O
, Clauss
M
, Does sexual selection shape sex differences in longevity and senescence patterns across vertebrates? A review and new insights from captive ruminants
. Evolution
. 2015
;69
(12
):3123
–40
.9.
Arbeev
KG
, Cohen
AA
, Arbeeva
LS
, Milot
E
, Stallard
E
, Kulminski
AM
, Optimal versus realized trajectories of physiological dysregulation in aging and their relation to sex-specific mortality risk
. Front Public Health
. 2016
;4
:3
. .10.
Arbeev
KG
, Ukraintseva
SV
, Akushevich
I
, Kulminski
AM
, Arbeeva
LS
, Akushevich
L
, Age trajectories of physiological indices in relation to healthy life course
. Mech Ageing Dev
. 2011
;132
(3
):93
–102
. .11.
Li
Q
, Wang
S
, Milot
E
, Bergeron
P
, Ferrucci
L
, Fried
LP
, Homeostatic dysregulation proceeds in parallel in multiple physiological systems
. Aging Cell
. 2015
;14
(6
):1103
–12
. .12.
Vidula
H
, Tian
L
, Liu
K
, Criqui
MH
, Ferrucci
L
, Pearce
WH
, Biomarkers of inflammation and thrombosis as predictors of near-term mortality in patients with peripheral arterial disease: a cohort study
. Ann Intern Med
. 2008
;148
(2
):85
–93
. .13.
Yang
Y
, Kozloski
M
. Change of sex gaps in total and cause-specific mortality over the life span in the United States
. Ann Epidemiol
. 2012
;22
(2
):94
–103
. .14.
Goldman
N
, Glei
DA
, Lin
YH
, Weinstein
M
. Improving mortality prediction using biosocial surveys
. Am J Epidemiol
. 2009
;169
(6
):769
–79
. .15.
Nakamura
E
, Miyao
K
. Sex differences in human biological aging
. J Gerontol A Biol Sci Med Sci
. 2008
;63
(9
):936
–44
. .16.
Yang
Y
, Kozloski
M
. Sex differences in age trajectories of physiological dysregulation: inflammation, metabolic syndrome, and allostatic load
. J Gerontol A Biol Sci Med Sci
. 2011
;66
(5
):493
–500
. .17.
Dallmeier
D
, Denkinger
M
, Peter
R
, Rapp
K
, Jaffe
AS
, Koenig
W
, Sex-specific associations of established and emerging cardiac biomarkers with all-cause mortality in older adults: the ActiFE study
. Clin Chem
. 2015
;61
(2
):389
–99
. .18.
Glei
DA
, Goldman
N
, Lin
YH
, Weinstein
M
. Age-related changes in biomarkers: longitudinal data from a population-based sample
. Res Aging
. 2011
;33
(3
):312
–26
. .19.
Cohen
AA
, Legault
V
, Li
Q
, Fried
LP
, Ferrucci
L
. Men sustain higher dysregulation levels than women without becoming frail
. J Gerontol A Biol Sci Med Sci
. 2018
;73
(2
):175
–84
. .20.
Dawson
KA
, Schneider
MA
, Fletcher
PC
, Bryden
PJ
. Examining gender differences in the health behaviors of Canadian university students
. J R Soc Promot Health
. 2007
;127
(1
):38
–44
. .21.
Lindahl-Jacobsen
R
, Hanson
HA
, Oksuzyan
A
, Mineau
GP
, Christensen
K
, Smith
KR
. The male-female health-survival paradox and sex differences in cohort life expectancy in Utah, Denmark, and Sweden 1850–1910
. Ann Epidemiol
. 2013
;23
(4
):161
–6
. .22.
Azevedo
MR
, Araújo
CL
, Reichert
FF
, Siqueira
FV
, da Silva
MC
, Hallal
PC
. Gender differences in leisure-time physical activity
. Int J Public Health
. 2007
;52
(1
):8
–15
. .23.
Martin
KR
, Koster
A
, Murphy
RA
, Van Domelen
DR
, Hung
MY
, Brychta
RJ
, Changes in daily activity patterns with age in U.S. men and women: National health and nutrition examination survey 2003–04 and 2005–06
. J Am Geriatr Soc
. 2014
;62
(7
):1263
–71
.24.
Varma
VR
, Dey
D
, Leroux
A
, Di
J
, Urbanek
J
, Xiao
L
, Re-evaluating the effect of age on physical activity over the lifespan
. Prev Med
. 2017
;101
:102
–8
. .25.
Elhakeem
A
, Cooper
R
, Whincup
P
, Brage
S
, Kuh
D
, Hardy
R
. Physical activity, sedentary time, and cardiovascular disease biomarkers at age 60 to 64 years
. J Am Heart Assoc
. 2018
;7
(16
):e007459
. .26.
Elhakeem
A
, Murray
ET
, Cooper
R
, Kuh
D
, Whincup
P
, Hardy
R
, Leisure-time physical activity across adulthood and biomarkers of cardiovascular disease at age 60–64: a prospective cohort study
. Atherosclerosis
. 2018
;269
:279
–87
.27.
Jarvie
JL
, Whooley
MA
, Regan
MC
, Sin
NL
, Cohen
BE
. Effect of physical activity level on biomarkers of inflammation and insulin resistance over 5 years in outpatients with coronary heart disease (from the heart and soul study)
. Am J Cardiol
. 2014
;114
(8
):1192
–7
. .28.
Gaudreau
P
, Morais
JA
, Shatenstein
B
, Gray-Donald
K
, Khalil
A
, Dionne
I
, Nutrition as a determinant of successful aging: description of the Quebec longitudinal study nuage and results from cross-sectional pilot studies
. Rejuvenation Res
. 2007
;10
(3
):377
–86
. .29.
Cohen
AA
, Li
Q
, Milot
E
, Leroux
M
, Faucher
S
, Morissette-Thomas
V
, Statistical distance as a measure of physiological dysregulation is largely robust to variation in its biomarker composition
. PLoS One
. 2015
;10
(4
):e0122541
. .30.
Khalil
A
, Gaudreau
P
, Cherki
M
, Wagner
R
, Tessier
DM
, Fulop
T
, Antioxidant-rich food intakes and their association with blood total antioxidant status and vitamin C and E levels in community-dwelling seniors from the Quebec longitudinal study NuAge
. Exp Gerontol
. 2011
;46
(6
):475
–81
. .31.
Washburn
RA
, Smith
KW
, Jette
AM
, Janney
CA
. The Physical Activity Scale for the Elderly (PASE): development and evaluation
. J Clin Epidemiol
. 1993
;46
(2
):153
–62
. .32.
Ware
JE
Jr., Sherbourne
CD
. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection
. Med Care
. 1992
;30
(6
):473
–83
. .33.
Hopman
WM
, Towheed
T
, Anastassiades
T
, Tenenhouse
A
, Poliquin
S
, Berger
C
, Canadian normative data for the SF-36 health survey. Canadian multicentre osteoporosis study research group
. CMAJ
. 2000
;163
(3
):265
–71
.34.
Desrosiers
J
, Bravo
G
, Hébert
R
, Dutil
E
. Normative data for grip strength of elderly men and women
. Am J Occup Ther
. 1995
;49
(7
):637
–44
. .35.
Chad
KE
, Reeder
BA
, Harrison
EL
, Ashworth
NL
, Sheppard
SM
, Schultz
SL
, Profile of physical activity levels in community-dwelling older adults
. Med Sci Sports Exerc
. 2005
;37
(10
):1774
–84
. .36.
Studenski
S
, Perera
S
, Wallace
D
, Chandler
JM
, Duncan
PW
, Rooney
E
, Physical performance measures in the clinical setting
. J Am Geriatr Soc
. 2003
;51
(3
):314
–22
. .37.
Cohen
AA
, Milot
E
, Li
Q
, Legault
V
, Fried
LP
, Ferrucci
L
. Cross-population validation of statistical distance as a measure of physiological dysregulation during aging
. Exp Gerontol
. 2014
;57
:203
–10
. .38.
Preacher
KJ
, Hayes
AF
. SPSS and SAS procedures for estimating indirect effects in simple mediation models
. Behav Res Methods Instrum Comput
. 2004
;36
(4
):717
–31
. .39.
Muniz-Terrera
G
, Robitaille
A
, Kelly
A
, Johansson
B
, Hofer
S
, Piccinin
A
. Latent growth models matched to research questions to answer questions about dynamics of change in multiple processes
. J Clin Epidemiol
. 2017
;82
:158
–66
. .40.
Allgayer
H
, Nicolaus
S
, Schreiber
S
. Decreased interleukin-1 receptor antagonist response following moderate exercise in patients with colorectal carcinoma after primary treatment
. Cancer Detect Prev
. 2004
;28
(3
):208
–13
. .41.
Allgayer
H
, Owen
RW
, Nair
J
, Spiegelhalder
B
, Streit
J
, Reichel
C
, Short-term moderate exercise programs reduce oxidative DNA damage as determined by high-performance liquid chromatography-electrospray ionization-mass spectrometry in patients with colorectal carcinoma following primary treatment
. Scand J Gastroenterol
. 2008
;43
(8
):971
–8
. .42.
Lee
DH
, de Rezende
LFM
, Eluf-Neto
J
, Wu
K
, Tabung
FK
, Giovannucci
EL
, Association of type and intensity of physical activity with plasma biomarkers of inflammation and insulin response
. Int J Cancer
. 2019 Jul 15
;145
(2
):360
–9
.43.
Celis-Morales
CA
, Perez-Bravo
F
, Ibañez
L
, Salas
C
, Bailey
ME
, Gill
JM
. Objective vs. self-reported physical activity and sedentary time: effects of measurement method on relationships with risk biomarkers
. PLoS One
. 2012
;7
(5
):e36345
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