Freeberg Kaitlin A, McCarty Narissa P, Chonchol Michel, Seals Douglas R, Craighead Daniel H
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States.
Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
J Appl Physiol (1985). 2025 Feb 1;138(2):536-545. doi: 10.1152/japplphysiol.00322.2024. Epub 2025 Jan 16.
Cerebrovascular disease and dementia risk increases with age, and lifetime risk is greater in women. Cerebrovascular dysfunction likely precedes cerebrovascular disease and dementia but the mechanisms are incompletely understood. We hypothesized that oxidative stress mediates cerebrovascular dysfunction with human aging. Internal carotid artery dilation (ICA dilation) and middle cerebral artery cerebrovascular reactivity (MCA CVR) in response to hypercapnia (5% CO) were measured in 20 young [10 F/10 M; age 23 ± 3 yr (means ± SD)] and 21 older (11 F/10 M; age 69 ± 9 yr) adults during intravenous infusions of saline (control) and vitamin C (acutely reduced oxidative stress condition). ICA dilation increased in response to vitamin C infusion in older adults (saline = 4.3 ± 2.4%; vitamin C = 6.7 ± 3.3%) but was unchanged in young adults (saline = 6.1 ± 2.7%; vitamin C = 5.5 ± 1.9%) (group × condition: = 0.004). MCA CVR was not different in response to vitamin C in either group (group × condition: = 0.341). However, when separated by sex, older female participants exhibited increased MCA CVR with vitamin C (saline = 0.85 ± 0.79 cm/s/mmHg; vitamin C = 1.33 ± 1.01 cm/s/mmHg) compared with older male participants (saline = 1.21 ± 0.57 cm/s/mmHg; vitamin C = 0.99 ± 0.47 cm/s/mmHg) (sex × condition: = 0.011). Oxidative stress selectively impairs cerebrovascular function in older adults in an artery- and sex-specific manner. This study is the first to report oxidative stress-mediated suppression of cerebrovascular reactivity to hypercapnia in the internal carotid artery in older compared with young adults. Overall, these in vivo findings identify oxidative stress as an important pathophysiological contributor to cerebrovascular aging in humans, highlighting the need to identify novel interventions that can reduce oxidative stress in the aging population.
脑血管疾病和痴呆风险随年龄增长而增加，女性的终生风险更高。脑血管功能障碍可能先于脑血管疾病和痴呆出现，但其机制尚未完全明确。我们推测氧化应激介导了人类衰老过程中的脑血管功能障碍。在20名年轻成年人[10名女性/10名男性；年龄23±3岁（均值±标准差）]和21名年长成年人（11名女性/10名男性；年龄69±9岁）静脉输注生理盐水（对照）和维生素C（急性降低氧化应激状态）期间，测量了颈内动脉扩张（ICA扩张）和大脑中动脉脑血管反应性（MCA CVR）对高碳酸血症（5%CO）的反应。年长成年人输注维生素C后ICA扩张增加（生理盐水组=4.3±2.4%；维生素C组=6.7±3.3%），而年轻成年人则无变化（生理盐水组=6.1±2.7%；维生素C组=5.5±1.9%）（组×状态：=0.004）。两组中维生素C对MCA CVR的影响无差异（组×状态：=0.341）。然而，按性别分开后，年长女性参与者维生素C组的MCA CVR增加（生理盐水组=0.85±o.o79cm/s/mmHg；维生素C组=1.33±1.01cm/s/mmHg），而年长男性参与者则为（生理盐水组=1.21±0.57cm/s/mmHg；维生素C组=0.99±0.47cm/s/mmHg）（性别×状态：=0.011）。氧化应激以动脉和性别特异性方式选择性损害年长成年人脑血管功能。本研究首次报告了与年轻成年人相比，年长成年人氧化应激介导的颈内动脉对高碳酸血症脑血管反应性的抑制。总体而言，这些体内研究结果表明氧化应激是人类脑血管衰老的重要病理生理因素，凸显了识别可降低老年人群氧化应激的新干预措施的必要性。
