2025.1.21
・Introduction
Mammals, including humans, have the adrenal glands. One gland each is located on the top of the left and right kidneys (Figure 1). Each layer of adrenal gland tissue produces various hormones that are important for biological activities (Figure 2), one of which is dehydroepiandrosterone (DHEA). Animal experiments demonstrated various effects of DHEA, such as preventing obesity, diabetes, and heart disease and enhancing the immune system1. However, the effects of oral supplementation with DHEA in humans reported lower effects than those observed in animals2,3.
Figure 1. Adrenal gland location. One gland is located on the top of each kidney.
Figure 2. Adrenal gland tissue. Each layer secretes hormones that are important for biological activities.
DHEA is a weakly active sex hormone, and most of it (>90%) exists as DHEA-S (DHEA sulfate) in the blood. Blood concentration of DHEA-S decreases with age. Large-scale epidemiological studies of residents from a specific region demonstrated that people with higher blood levels of DHEA-S may have longer life expectancy4,5. These findings suggest that the DHEA-producing cell function and aging may be related to human life expectancy.
Therefore, we have conducted studies using human adrenal glands. The results of our previous studies are summarized below.
・Relationship between DHEA-producing Cell Aging and Life Expectancy
Telomeres are repetitive DNA sequences that protect the ends of eukaryotic chromosomes (Figure 3). These telomere lengths shorten each time a cell divides, and once they reach a critical length, the cell can no longer divide. The process is called cell aging; telomere shortening is an essential marker of cell aging.
Figure 3. Telomeres. Telomeres are noncoding repetitive DNA sequences located at the ends of all eukaryotic chromosomes and play a pivotal role in preventing genomic instability. Telomere lengths in most somatic cells shorten with each cell division.
This study used pathological autopsy adrenal glands to measure telomere length in males and females aged from infants to over 100 years old for the four types of cells shown in Figure 26,7. The results demonstrated that in both males and females, the telomeres of Zona reticularis (ZR) cells that produced DHEA were longer in older subjects (Figure 4). This suggests that longer telomeres in ZR cells (i.e., less aging of ZR cells) may be associated with longer life expectancy in both males and females.
Figure 4. Correlation between telomere length in each layer of adrenal glands and age (by sex). The telomere length for ZR cells was significantly increased with age, whereas no significant age-related changes were detected in telomere lengths for the other 3 types of adrenal cells. ZG, Zona glomerulosa; ZF, Zona fasciculata; ZR, Zona reticularis.
・Chronic Stress Accelerates the Aging of DHEA-producing Cells
Chronic psychological stress shortens the length of telomeres of peripheral blood cells8. However, the correlation between chronic stress and adrenal gland cell aging is unknown. As patients who passed away from a prolonged critical illness are likely to have been subjected to strong psychological and physical chronic stress, we used the adrenal glands of such patients and the adrenal glands of patients who died suddenly to compare telomere length by cell type9. Results showed that in both males and females, the telomere length of ZR cells that produce DHEA was shortened in patients with a prolonged critical illness compared to patients who died suddenly (Figure 5). No changes were noted in the length of telomeres of other three types of cells. This suggests that the aging process of ZR cells is accelerated under conditions of intense, chronic stress, such as a prolonged critical illness.
Figure 5. Box plots representing the telomere lengths in four types of adrenal parenchymal cells. Telomere lengths of the same type of adrenal parenchymal cells were compared between the control and prolonged critical illness (PCI) groups. Telomere lengths in ZR cells (i.e., DHEA-producing cells) were significantly shorter in the PCI group than in the control group for both men and women. ZG, Zona glomerulosa; ZF, Zona fasciculata; ZR, Zona reticularis.
Conclusions
This "Research topic" introduced correlations between the aging of adrenal gland ZR cells that produce DHEA, human life expectancy, and chronic stress. As the definition of chronic stress remains vague, ongoing research must clarify what types of illnesses or test data are related to the aging of DHEA-producing cells. The author hopes that this research will contribute to lengthening healthy life expectancy and preventing chronic stress.
References
