TY - JOUR
T1 - Men sustain higher dysregulation levels than women without becoming frail
AU - Cohen, Alan A.
AU - Legault, Véronique
AU - Li, Qing
AU - Fried, Linda P.
AU - Ferrucci, Luigi
N1 - Funding Information:
This work was supported by catalyst grant on biological differences between the sexes from the Canadian Institutes of Health Research (CIHR) (grant number SVB-145585). AAC is also supported by a CIHR New Investigator Salary Award and is a member of the Fonds de recherche du Québec – Santé funded Centre de recherche du CHUS and Centre de recherche sur le vieillissement.
Publisher Copyright:
© The Author(s) 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights
PY - 2018/3/1
Y1 - 2018/3/1
N2 - The aging process differs in important ways between the sexes, with women living longer but at higher risk for frailty (the male-female health-survival paradox). The underlying biological mechanisms remain poorly understood, but may relate to sex differences in physiological dysregulation patterns. Here, using biomarkers from two longitudinal cohort studies (InCHIANTI and BLSA) and one cross-sectional survey (NHANES), we assess sex differences in trajectories of dysregulation globally and for five physiological systems: oxygen transport, electrolytes, hematopoiesis, lipids, and liver/kidney function. We found higher dysregulation levels in men, both globally and in the oxygen transport and hematopoietic systems (p < .001 for all), though differences for other systems were mixed (electrolytes) or absent (lipids and liver/kidney). There was no clear evidence for sex differences in rates of change in dysregulation with age. Although risk of frailty and mortality increase with dysregulation, there was no evidence for differences in these effects between sexes. These findings imply that the greater susceptibility of women to frailty is not simply due to a tolerance for higher dysregulation; rather, it may actually be men that have a greater tolerance for dysregulation, creating a male-female dysregulation-frailty paradox. However, the precise physiological mechanisms underlying the sex differences appear to be diffuse and hard to pin down.
AB - The aging process differs in important ways between the sexes, with women living longer but at higher risk for frailty (the male-female health-survival paradox). The underlying biological mechanisms remain poorly understood, but may relate to sex differences in physiological dysregulation patterns. Here, using biomarkers from two longitudinal cohort studies (InCHIANTI and BLSA) and one cross-sectional survey (NHANES), we assess sex differences in trajectories of dysregulation globally and for five physiological systems: oxygen transport, electrolytes, hematopoiesis, lipids, and liver/kidney function. We found higher dysregulation levels in men, both globally and in the oxygen transport and hematopoietic systems (p < .001 for all), though differences for other systems were mixed (electrolytes) or absent (lipids and liver/kidney). There was no clear evidence for sex differences in rates of change in dysregulation with age. Although risk of frailty and mortality increase with dysregulation, there was no evidence for differences in these effects between sexes. These findings imply that the greater susceptibility of women to frailty is not simply due to a tolerance for higher dysregulation; rather, it may actually be men that have a greater tolerance for dysregulation, creating a male-female dysregulation-frailty paradox. However, the precise physiological mechanisms underlying the sex differences appear to be diffuse and hard to pin down.
KW - Biomarker
KW - Dysregulation trajectory
KW - Homeostasis
KW - Physiological systems
KW - Statistical distance
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U2 - 10.1093/gerona/glx146
DO - 10.1093/gerona/glx146
M3 - Article
C2 - 28977345
AN - SCOPUS:85045981635
SN - 1079-5006
VL - 73
SP - 175
EP - 184
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 2
ER -