Effect of age on long-term facilitation and chemosensitivity during NREM sleep

Abstract

The reason for increased sleep-disordered breathing with a predominance of central apneas in the elderly is unknown. We speculate that ventilatory control instability may provide a link between aging and the onset of unstable breathing during sleep. We sought to investigate potential underlying mechanisms in healthy, elderly adults during sleep. We hypothesized that there is 1) a decline in respiratory plasticity or long-term facilitation (LTF) of ventilation and/or 2) increased ventilatory chemosensitivity in older adults during non-, this should be hyphenated, non-rapid rapid eye movement (NREM) sleep. Fourteen elderly adults underwent 15, 1-min episodes of isocapnic hypoxia (EH), nadir O2 saturation: 87.0 ± 0.8%. Measurements were obtained during control, hypoxia, and up to 20 min of recovery following the EH protocol, respectively, for minute ventilation (VI), timing, and inspiratory upper-airway resistances (RUA). The results showed the following. 1) Compared with baseline, there was a significant increase in VI (158 ± 11%, P < 0.05) during EH, but this was not accompanied by augmentation of VI during the successive hypoxia trials nor in VI during the recovery period (94.4 ± 3.5%, P = not significant), indicating an absence of LTF. There was no change in inspiratory RUA during the trials. This is in contrast to our previous findings of respiratory plasticity in young adults during sleep. Sham studies did not show a change in any of the measured parameters. 2) We observed increased chemosensitivity with increased isocapnic hypoxic ventilatory response and hyperoxic suppression of VI in older vs. young adults during NREM sleep. Thus increased chemosensitivity, unconstrained by respiratory plasticity, may explain increased periodic breathing and central apneas in elderly adults during NREM sleep.

Aging is associated with increased propensity for central apnea during NREM sleep

“…Instead, we noted increased hypocapnic chemoreflex sensitivity during sleep in elderly adults relative to the younger group, indicative of increased central chemoreceptor activity. These findings corroborate our previous findings demonstrating increased peripheral chemoreceptor activity in older adults (16).…”

“…In a separate study, steady-state loop gain was also lower in older vs. younger OSA patients (22). Conversely, we have demonstrated that the elderly have higher peripheral chemoresponsiveness than young adults (16), which may contribute to increased periodic breathing. Given the conflicting findings, it is important to clarify the underlying pathophysiology for SDB in the elderly, which may inform targeted therapies of sleep apnea in the elderly.…”

“…Peripheral chemoreflex sensitivity may also contribute to the development of central apnea. We have previously demonstrated age-related increase in peripheral chemosensitivity, as evidenced by increased isocapnic hypoxic ventilatory response and hyperoxic suppression of ventilation during NREM sleep, compared with young adults (16). Thus the combination of increased chemosensitivity and reduced cerebrovascular responsiveness to CO 2 may explain the narrow CO 2 reserve and increased propensity for central apneas in elderly individuals during sleep.…”

“…Results of linear regression analyses adjusted for BMI that zolpidem influences ventilatory parameters during sleep(7,16,32,37,57). Zolpidem is a nonbenzodiazepine GABA receptor agonist.…”

A comprehensive review of respiratory, autonomic and cardiovascular responses to intermittent hypoxia in humans

“…Chowdhuri and colleagues demonstrated in humans that aging is linked to a reduction in the magnitude of long-term facilitation during non-rapid eye movement sleep since long-term facilitation was found in young but not older men ( Chowdhuri et al, 2015 ; Chowdhuri et al, 2010 ). The authors suggested that the absence of ventilatory long-term facilitation in older adults during sleep could be due to an age-dependent decline in raphe neuronal activity, reduced availability of serotonin, or an age-related decrease in serum testosterone levels in older men ( Chowdhuri et al, 2015 ; Chowdhuri et al, 2010 ). However, their study was not designed to tease out the relative contribution of age vs. reduction in sex hormone levels on the magnitude of ventilatory long-term facilitation.…”