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Sexual dimorphic impact of adult-onset somatopause on life span and age-induced osteoarthritis.

ABSTRACT: Osteoarthritis (OA), the most prevalent joint disease, is a major cause of disability worldwide. Growth hormone (GH) has been suggested to play significant roles in maintaining articular chondrocyte function and ultimately articular cartilage (AC) homeostasis. In humans, the age-associated decline in GH levels was hypothesized to play a role in the etiology of OA. We studied the impact of adult-onset isolated GH deficiency (AOiGHD) on the life span and skeletal integrity including the AC, in 23- to 30-month-old male and female mice on C57/BL6 genetic background. Reductions in GH during adulthood were associated with extended life span and reductions in body temperature in female mice only. However, end-of-life pathology revealed high levels of lymphomas in both sexes, independent of GH status. Skeletal characterization revealed increases in OA severity in AOiGHD mice, evidenced by AC degradation in both femur and tibia, and significantly increased osteophyte formation in AOiGHD females. AOiGHD males showed significant increases in the thickness of the synovial lining cell layer that was associated with increased markers of inflammation (IL-6, iNOS). Furthermore, male AOiGHD showed significant increases in matrix metalloproteinase-13 (MMP-13), p16, and β-galactosidase immunoreactivity in the AC as compared to controls, indicating increased cell senescence. In conclusion, while the life span of AOiGHD females increased, their health span was compromised by high-grade lymphomas and the development of severe OA. In contrast, AOiGHD males, which did not show extended life span, showed an overall low grade of lymphomas but exhibited significantly decreased health span, evidenced by increased OA severity.

SUBMITTER: Poudel SB

PROVIDER: S-EPMC8373322 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Typical cognitive aging may be defined as age-associated changes in cognitive performance in individuals who remain free of dementia. Ideally, the full adult age spectrum should be included to assess brain imaging findings associated with typical aging.To compare age, sex, and APOE ?4 effects on memory, brain structure (adjusted hippocampal volume [HVa]), and amyloid positron emission tomography (PET) in cognitively normal individuals aged 30 to 95 years old.Cross-sectional observational study (March 2006 to October 2014) at an academic medical center. We studied 1246 cognitively normal individuals, including 1209 participants aged 50 to 95 years old enrolled in a population-based study of cognitive aging and 37 self-selected volunteers aged 30 to 49 years old.Memory, HVa, and amyloid PET.Overall, memory worsened from age 30 years through the 90s. The HVa worsened gradually from age 30 years to the mid-60s and more steeply beyond that age. The median amyloid PET was low until age 70 years and increased thereafter. Memory was worse in men than in women overall (P <?.001) and more specifically beyond age 40 years. The HVa was lower in men than in women overall (P <?.001) and more specifically beyond age 60 years. There was no sex difference in amyloid PET at any age. Within each sex, memory performance and HVa were not different by APOE ?4 status at any age. From age 70 years onward, APOE ?4 carriers had significantly greater median amyloid PET than noncarriers. However, the ages at which 10% of the population were amyloid PET positive were 57 years for APOE ?4 carriers and 64 years for noncarriers.Male sex is associated with worse memory and HVa among cognitively normal individuals, while APOE ?4 is not. In contrast, APOE ?4 is associated with greater amyloid PET (from age 70 years onward), while sex is not. Worsening memory and HVa occur at earlier ages than abnormal amyloid PET. Therefore, neuropathological processes other than ?-amyloidosis must underlie declines in brain structure and memory function in middle age. Our findings are consistent with a model of late-onset Alzheimer disease in which ?-amyloidosis arises in later life on a background of preexisting structural and cognitive decline that is associated with aging and not with ?-amyloid deposits.

Project description:BackgroundAdult-onset isolated focal dystonia (AOIFD) presenting in early adult life is more frequent in men, whereas in middle age it is female predominant. Temporal discrimination, an endophenotype of adult-onset idiopathic isolated focal dystonia, shows evidence of sexual dimorphism in healthy participants.ObjectivesWe assessed the distinctive features of age-related sexual dimorphism of (i) sex ratios in dystonia phenotypes and (ii) sexual dimorphism in temporal discrimination in unaffected relatives of cervical dystonia patients.MethodsWe performed (i) a meta-regression analysis of the proportion of men in published cohorts of phenotypes of adult-onset dystonia in relation to their mean age of onset and (ii) an analysis of temporal discrimination thresholds in 220 unaffected first-degree relatives (125 women) of cervical dystonia patients.ResultsIn 53 studies of dystonia phenotypes, the proportion of men showed a highly significant negative association with mean age of onset (p < 0.0001, pseudo-R (2) = 59.6%), with increasing female predominance from 40 years of age. Age of onset and phenotype together explained 92.8% of the variance in proportion of men. Temporal discrimination in relatives under the age of 35 years is faster in women than men but the age-related rate of deterioration in women is twice that of men; after 45 years of age, men have faster temporal discrimination than women.ConclusionTemporal discrimination in unaffected relatives of cervical dystonia patients and sex ratios in adult-onset dystonia phenotypes show similar patterns of age-related sexual dimorphism. Such age-related sexual dimorphism in temporal discrimination and adult-onset focal dystonia may reflect common underlying mechanisms. Cerebral GABA levels have been reported to show similar age-related sexual dimorphism in healthy participants and may be the mechanism underlying the observed age-related sexual dimorphism in temporal discrimination and the sex ratios in AOIFD.

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Sexual dimorphic impact of adult-onset somatopause on life span and age-induced osteoarthritis.

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