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Regional specificity of sex effects on subcortical volumes across the lifespan in healthy aging.

ABSTRACT: When conceptualizing age-specific onsets and sex-specific characteristics of neuropsychiatric diseases in a neurobiological context, it may be crucially important to consider differential trajectories of aging. Here, we investigated effects of age, sex, and their interactions on absolute and relative volumes of subcortical structures with known involvement in psychiatric disorders, including the basal ganglia, thalamus, hippocampus, and amygdala. Structural MRI data of 76 healthy subjects (38 males, 19-70 years) from the ICBM database were analyzed. Age-related absolute atrophy was generally found in the basal ganglia and thalamus, while in the hippocampus decline was only observed in males, and was generally absent in the amygdala. Disproportionate degeneration in the basal ganglia and thalamus, exceeding cortical decline was specific for females. When allowing higher-order models, a quadratic model could better describe the negative relation of absolute volume and age in the basal ganglia in males, and generally in the hippocampus and amygdala. We could show that negative age-relations are highly specific for certain subcortical structures in either gender. Importantly these findings also emphasize the significant impact of analytical strategies when deciding for correction of subcortical volumes to the whole-brain decline. Specifically, in the basal ganglia disproportionate shrinkage in females was suggested by the relative analysis while absolute volume analysis rather stressed an accelerating decline in older males. Given strong involvement of the basal ganglia in both cognitive aging and emotional regulation, our findings may be crucial for studies investigating the onset and prevalence of dementia and depressive symptoms in male and female aging.

SUBMITTER: Li W

PROVIDER: S-EPMC6869103 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Regional specificity of sex effects on subcortical volumes across the lifespan in healthy aging.

Li Wenjing W van Tol Marie-José MJ Li Meng M Miao Wen W Jiao Yonghong Y Heinze Hans-Jochen HJ Bogerts Bernhard B He Huiguang H Walter Martin M

Human brain mapping 20120921 1

When conceptualizing age-specific onsets and sex-specific characteristics of neuropsychiatric diseases in a neurobiological context, it may be crucially important to consider differential trajectories of aging. Here, we investigated effects of age, sex, and their interactions on absolute and relative volumes of subcortical structures with known involvement in psychiatric disorders, including the basal ganglia, thalamus, hippocampus, and amygdala. Structural MRI data of 76 healthy subjects (38 ma ...[more]

PMID: 22996803

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Project description:PurposeIn an increasingly aging society, it is of great importance to consider trajectories of subcortical volumes at different ages for understanding biological markers of aging. Thus, we investigated sex, age, and their interactions on subcortical volumes, including the basal ganglia (caudate, putamen, accumbens, and pallidum), thalamus, hippocampus, and amygdala.MethodsWe analyzed the adult lifespan trajectory of subcortical volumes and asymmetries in 563 healthy subjects aged from 19 to 86 using magnetic resonance imaging (MRI) data from the publicly available 7IXI data set.ResultsThe sex made strong contributions to the trajectories of subcortical volumes with aging, including the right putamen, right pallidum, bilateral thalamus, hippocampus, and amygdala. The volume of the right putamen, right pallidum, and right thalamus decreased more rapidly in males than in females, and the volume of the left thalamus, bilateral hippocampus, and amygdala in males followed a quadratic model, while those in females followed a linear decline model. The asymmetries in the caudate and hippocampus showed a linear decline, and a sex and age interaction was found in the hippocampus; that is, the asymmetry in the hippocampus decreased only in the males and not in the females. Changes in the accumbens and pallidum fit quadratic trajectories, in which females increased until 39.26 years old in the accumbens asymmetry and then began to rapidly decline, and males showed a linear decline. The asymmetry in the pallidum in males and females showed a slow decreasing period until almost 45 years of age and then increased.ConclusionThe results suggest that compared with females, males have a faster decline in the volume of the right putamen, right pallidum, and right thalamus, while aging occurred later but also faster in the left thalamus, bilateral hippocampus, and amygdala. Interestingly, we found the inflection point in the thalamus, bilateral hippocampus, and amygdala volume in the quadratic model, and after this point, the volume change accelerated with aging, which may have resulted from the stronger work pressure in the middle-aged men and the low levels of testosterone in the older adults. The interaction of age and sex on individual subcortical structures provides evidence to support the impact of sex on psychopathologies associated with degenerative brain disorders in the elderly. The findings may be significant to investigate the occurrence and prevalence of degenerative brain disorders in males and females. Future studies can focus on the functional and behavioral relations with subcortical structures for preventive measures of related disorders.

Project description:BackgroundDepression is a widely prevalent, often recurrent condition. To analyze the regional differences in depressive symptoms over time, we investigated urban-rural differences in change in depression over time in South Korea and the association between healthy aging and depressive symptoms among middle-aged and older adults.MethodsData collected in the Korean Longitudinal Study of Aging, from 2006 to 2020, of adult participants aged ≥45 years without depressive symptoms were analyzed. Healthy aging was defined under five principal components: absence of chronic disease, good physical function, normal cognitive function, active social engagement, and good psychological adaptation. Depressive symptoms were measured using the short version of the Center for Epidemiologic Studies Depression Scale. Using the Andersen-Gill model for recurrent time-to-event, we examined the effect of healthy aging on depressive symptoms, with a subgroup analysis based on the residential area.ResultsOf the 7,708 participants, 78.2% lived in urban areas and 39.4% achieved healthy aging. In 2008, rural residents had a higher incidence of depressive symptoms (rural 11.8%; urban 8.9%); however, after 2016, the depressive symptoms of urban residents gradually increased (rural 6.4%; urban 12.1%). Unhealthy aging (adjusted hazard ratio = 3.04, 95% confidence interval: 2.72-3.39) and urban residence (adjusted hazard ratio = 1.15, 95% confidence interval: 1.06-1.24) were risk factors for depressive symptoms. The subgroup analysis revealed that individuals who did not achieve healthy aging had an increased risk of depressive symptoms, regardless of their residential area (hazard ratio [95% confidence interval]: urban, 3.13 [2.75-3.55]; rural 2.59 [2.05-3.28]).ConclusionAs urbanization accelerates, urban residents have a higher risk of depressive symptoms than rural residents. Healthy aging is an essential factor in reducing depressive symptoms. To achieve healthy aging, appropriate interventions and policies that target the middle-aged adults and gradually extend to older adults are needed, considering individual and regional factors.

Project description:Impairments of various aspects of mitochondrial function have been associated with increased lifespan in various model organisms ranging from Caenorhabditis elegans to mice. For example, disruption of the function of the 'Rieske' iron-sulfur protein (RISP) of complex III of the mitochondrial electron transport chain can result in increased lifespan in the nematode worm C. elegans. However, the mechanisms by which impaired mitochondrial function affects aging remain under investigation, including whether or not they require decreased electron transport. We have generated knock-in mice with a loss-of-function Risp mutation that is homozygous lethal. However, heterozygotes (Risp(+/P224S)) were viable and had decreased levels of RISP protein and complex III enzymatic activity. This decrease was sufficient to impair mitochondrial respiration and to decrease overall metabolic rate in males, but not females. These defects did not appear to exert an overtly deleterious effect on the health of the mutants, since young Risp(+/P224S) mice are outwardly normal, with unaffected performance and fertility. Furthermore, biomarkers of oxidative stress were unaffected in both young and aged animals. Despite this, the average lifespan of male Risp(+/P224S) mice was shortened and aged Risp(+/P224S) males showed signs of more rapidly deteriorating health. In spite of these differences, analysis of Gompertz mortality parameters showed that Risp heterozygosity decreased the rate of increase of mortality with age and increased the intrinsic vulnerability to death in both sexes. However, the intrinsic vulnerability was increased more dramatically in males, which resulted in their shortened lifespan. For females, the slower acceleration of age-dependent mortality results in significantly increased survival of Risp(+/P224S) mice in the second half of lifespan. These results demonstrate that even relatively small perturbations of the mitochondrial electron transport chain can have significant physiological effects in mammals, and that the severity of those effects can be sex-dependent.

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Regional specificity of sex effects on subcortical volumes across the lifespan in healthy aging.

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Regional specificity of sex effects on subcortical volumes across the lifespan in healthy aging.

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