Tier 3 — preclinical

Effects of regular exercise on vascular function with aging: Does sex matter?

Moreau KL, Clayton ZS, DuBose LE, Rosenberry R, Seals DR
American Journal of Physiology-Heart and Circulatory Physiology 2023 326(1):H123-H137

Bibliography

PubMed
PMID 37921669
PubMed Central
PMC11208002
DOI
10.1152/ajpheart.00392.2023
Funding
K.L.M. is supported by NIH grants R01AG027678, R56AG072094, and R01AG049762. Z.S.C. is supported by NIH grants F32HL151022, K99HL159241, and F32AG071273. L.E.D. is supported by NIH grants K12AR084226 and T32AG000279. D.R.S. is supported by NIH grants R01AG055822, R01AG066151, R01AG073117, R01AG066730, and R21AG078408, and by the Eastern Colorado VA Geriatric Research, Education and Clinical Center (GRECC).
Competing interests
No conflicts of interest, financial or otherwise, are declared by the authors.

Study snapshot

DesignNarrative review
ModelHuman vascular ageing studies (middle-aged/older men and women, pre- and post-menopausal) plus mechanistic/animal evidence on oestrogen-eNOS signalling
SampleN/A - review
InterventionN/A - review of aerobic and resistance exercise training studies
DurationN/A - review
EndpointsEndothelial function and nitric oxide bioavailability by sex and menopausal status; Arterial stiffness response to aerobic exercise training by sex; Oxidative stress and inflammation as mediators of sex differences in vascular ageing

What the study showed, in plain terms

Nitric oxide's role in keeping blood vessels healthy doesn't work identically in men and women as we age. In women, oestrogen helps support the enzyme that makes nitric oxide (eNOS), so vascular function tends to hold up reasonably well until menopause, after which decline accelerates. Regular aerobic exercise reliably improves nitric-oxide-dependent vascular function in ageing men, but this same benefit is often blunted or absent in oestrogen-deficient postmenopausal women, suggesting sex-specific biology matters for how well exercise protects blood vessels with age.

Key findings

  • Vascular ageing is driven substantially by oxidative stress that reduces nitric oxide bioavailability, but sex hormones modulate how and when this occurs.
  • In women, declining oestrogen with menopause interacts with the ageing process to worsen endothelial dysfunction; oestrogen supports eNOS-derived nitric oxide production through genomic and non-genomic mechanisms.
  • Regular aerobic exercise consistently improves nitric-oxide-mediated endothelial function in ageing men, but this benefit is inconsistent or absent in oestrogen-deficient postmenopausal women.
  • Treating postmenopausal women with oestradiol has been shown to restore the ability of aerobic exercise to improve nitric-oxide-mediated endothelial function.
  • Considerable research gaps remain in understanding the mechanisms behind these sex differences and how to design sex-specific exercise interventions.

What this study can and cannot tell us

This is a narrative synthesis rather than a systematic review, drawing substantially on the authors' own research programme, which may shape emphasis. Much of the mechanistic detail on oestrogen-eNOS signalling comes from animal and in vitro work rather than direct human measurement, and evidence on male sex-hormone (testosterone) effects on vascular nitric oxide signalling is comparatively sparse.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology