APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia

FUNCTION, 2023 · DOI: 10.1093/function/zqad026 · Published: June 13, 2023

Simple Explanation

This study explores how genetics, age, and sex influence the effectiveness of a therapy called acute intermittent hypercapnic-hypoxia (AIHH) to improve breathing in healthy adults. The researchers found that individuals with a specific gene variation (APOE4) showed less improvement in diaphragm function after AIHH. Also, men generally had a better response than women, and younger individuals showed more benefit than older ones. These findings suggest that personalized approaches, considering genetics, age, and sex, may be necessary to optimize the benefits of AIHH therapy for respiratory rehabilitation.

Study Duration

Not specified

Participants

17 healthy individuals (age = 27 ± 5 yr)

Evidence Level

Level Not specified, Human and animal study

Key Findings

1
Individuals heterozygous for APOE4 showed lower AIHH-induced changes in diaphragm MEP amplitudes.
2
Males exhibited greater diaphragm MEP enhancement versus females, regardless of age.
3
Age was inversely related with change in P0.1, indicating a decline in respiratory drive with age.

Research Summary

The study investigated the influence of genetics, age, and sex on respiratory motor plasticity induced by AIHH in healthy adults. Results showed that the APOE4 genotype, sex, and age are significant determinants of AIHH-induced respiratory motor plasticity. Animal experiments confirmed a causal link between the APOE4 allele and impaired respiratory motor plasticity after AIHH.

Practical Implications

Personalized Rehabilitation

Genetic screening for APOE4 could help identify individuals less likely to respond to AIHH, allowing for alternative or adjusted therapeutic strategies.

Sex-Specific Protocols

Given the differential responses between males and females, rehabilitation protocols may need to be tailored to optimize outcomes based on sex.

Age-Related Considerations

Rehabilitation strategies should consider the age-related decline in respiratory drive to maximize the effectiveness of AIHH therapy in older individuals.

Study Limitations

1
Moderate AIHH protocol has not been previously studied in humans.
2
The menstrual cycle phase in female participants was not controlled in this study.
3
Humans studied here included a number of individuals that were heterozygous for APOE4, whereas the knock-in rats studied were homozygous for the human APOE4 allele.

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