Correlation Between Telomere Attrition of Zona Fasciculata and Adrenal Weight Reduction in Older Men

Abstract

Context Although numerous theories are reported on sex differences in longevity, the underlying biological mechanisms remain unknown. We previously reported that telomere length in the zona reticularis cells of the human adrenal cortex was significantly longer in older than that in younger subjects. However, we could not evaluate sex differences in the telomere lengths. Objective To compare the telomere lengths of adrenocortical and adrenal medullar cells between men and women from infancy through older adulthood. Methods Adrenal glands of 30 male (aged 0 to 100 years) and 25 female (aged 0 to 104 years) autopsied subjects were retrieved from autopsy files. Using quantitative fluorescence in situ hybridization, relative telomere lengths were determined in the parenchymal cells of the 3 adrenocortical zones and medulla. Age-related changes in the weight of adrenal glands were also investigated. Main results Older male subjects (aged 65 years or older) had significantly shorter telomere lengths in zona fasciculata (ZF) cells compared to the corresponding female subjects. In men, older subjects exhibited a significant age-related reduction in adrenal weight; however, no age-related changes in adrenal weight were detected in women. Conclusion Telomere attrition of ZF cells was correlated with adrenal weight reduction in older men but not in older women, suggesting a decreased number of ZF cells in older men. This may help us understand the possible biological mechanisms of sex difference in longevity of humans.

The Sexually Dimorphic Adrenal Cortex: Implications for Adrenal Disease

“…Human adrenals harbor very low levels of telomerase activity. Despite this, older men (>65 years old) have significantly shorter telomere lengths in the zona fasciculata compared with the corresponding female subjects [ 78 ]. Telomere attrition in ageing men might contribute to the reduction in adrenal weight that is observed in this age group [ 78 ].…”

“…Despite this, older men (>65 years old) have significantly shorter telomere lengths in the zona fasciculata compared with the corresponding female subjects [ 78 ]. Telomere attrition in ageing men might contribute to the reduction in adrenal weight that is observed in this age group [ 78 ]. Of note, zR displays the longest telomeres among the adrenocortical zones, and their length appears to increase rather than decrease with age [ 79 ].…”

Age-related Changes in the Adrenal Cortex: Insights and Implications

“…After peak growth, adrenal weight dramatically declined in males, but regressed at a slower rate in females. This trend is also observed in various mammalian models and human clinical samples where adrenal weight decreases in an aged setting and is accelerated in males [ 23 , 24 ]. Additionally, data from our own laboratory confirm that adult C57BL/6J female adrenals are larger when compared to that of males, and male adrenal weight significantly decreases with advanced aging up to 78 weeks [ 25 ].…”

“…A Japanese study measured telomere length, which is commonly shortened in senescent cells [ 112 ]. This study reported an unexpected age-associated increase in telomere length in the zR compared with the zG and zF, and also showed a modest increase in zR telomere length with age in males and females [ 24 , 113 ]. This is surprising given that cells of the zR are expected to be the longest-lived adrenal cortex cells and telomere lengthening is quite unusual.…”

“…This is surprising given that cells of the zR are expected to be the longest-lived adrenal cortex cells and telomere lengthening is quite unusual. However, the analysis was conducted using hematoxylin-eosin staining as opposed to using zonal-specific protein markers, and the authors also note the zR exhibiting autofluorescent lipofusin [ 24 ]. Therefore, some cells contained within the histological zR could be newly recruited myeloid cells, given this distinct adrenal feature (discussed earlier).…”