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Biology subjects

Lynch, M. E.

Publications and source records attributed to Lynch, M. E..

3 recordsLinked to original sources

Epigenetic and neural correlates of selective social attention across adulthood

Social isolation is one of the strongest predictors of increased risk of mortality in older adulthood. The ability to form and maintain the social relationships that mitigate this risk is partially regulated by the oxytocinergic system and ones ability to attend to and process social information. We have previously shown that an epigenetic change to the DNA of the oxytocin receptor gene (OXTR methylation) affects the salience of social information in young adults. Little is known about how the oxytocinergic system ages and what effect this aging system has on social cognitive abilities throughout the lifespan. Here we explore age-related differences in the association between neural response during selective social attention and OXTR DNA methylation in young and older adults. We find that older adults activate diffuse areas of visual cortex and dorsolateral prefrontal cortex during selective social attention, consistent with the dedifferentiation and compensatory neural activation commonly reported in aging. We find a significant age-by-OXTR methylation interaction on neural response when attending to social stimuli in a complex display; young adults display a positive association between OXTR methylation and neural activation, replicating our prior finding that young adults with presumed diminished endogenous access to oxytocin recruit regions of the attentional cortex to a greater extent. This association does not hold for older adults. Instead, perceived social support interacts with OXTR methylation to influence neural response during selective social attention. These data suggest that environmental factors like social support moderate biological processes in aging and highlight the importance of a lifespan perspective for understanding associations between individual differences in the oxytocinergic system, neural function, and social behavior.

neuroscience↗

Epigenetic age acceleration predicts subject-specific white matter degeneration in the human brain.

Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. Given the blood plasma correlations used to develop GrimAge, a specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individuals brain affected by their unique white matter hyperintensity location and volume. 98 subjects over 55 years of age were scanned at baseline with 41 returning for a follow-up scan 2 years later. Using diffusion MRI lesionometry, we reconstructed subject-specific networks of affected axonal tracts and examined the diffusion cellular microstructure composition of these areas, both at baseline and longitudinally, for evidence of cellular degeneration. A chronological age-adjusted version of GrimAge was significantly correlated with baseline WMH volume and markers of neuronal decline, indicated by increased extracellular free water, increased intracellular signal, and decreased axonal signal within WMH. By isolating subject-specific axonal regions lesioned by crossing through a WMH, age-adjusted GrimAge was also able to predict longitudinal development of similar patterns of neuronal decline throughout the brain. This study is the first to establish a relationship between accelerated epigenetic GrimAge and brain cellular microstructure in humans.

neuroscience↗

Reduced local mechanical stimuli in spaceflight diminishes osteocyte lacunar morphometry and spatial heterogeneity in mouse cortical bone

Three-dimensional (3D) imaging of osteocyte lacunae has recently substantiated the connection between lacunar shape and size, and osteocyte age, viability, and mechanotransduction. Yet it remains unclear why individual osteocytes reshape their lacunae and how networks of osteocytes change in response to local alterations in mechanical loads. We evaluated the effects of local mechanical stimuli on osteocyte lacunar morphometrics in tibial cortical bone from young female mice flown on the Space Shuttle for [~]13 days. We optimized scan parameters, using a laboratory-based submicrometer-resolution X-Ray Microscope, to achieve large [~] 0.3 mm3 fields of view with sufficient resolution ([≥] 0.3 m) to visualize and measure thousands of lacunae per scan. Our novel approach avoids large measurement errors that are inherent in 2D and enables a facile 3D solution as compared to the lower resolution from benchtop micro-computed tomography (CT) systems or the cost and inaccessibility of synchrotron-based CT. Osteocyte lacunae were altered following microgravity exposure in a region-specific manner: more elongated (+7.0% Stretch) in predominately tensile-loaded bone as compared to those in compressively-loaded regions. In compressively-loaded bone, lacunae formed in microgravity were significantly larger (+6.9% Volume) than in the same region formed on Earth. We also evaluated lacunar heterogeneity (i.e., spatial autocorrelation of lacunar morphometric parameters) via kriging models. These statistical models demonstrated that heterogeneity varied with underlying spatial contributors, i.e. the local mechanical and biological environment. Yet in the absence of gravitational loading, osteocyte lacunae in newly formed bone were larger and were collectively more homogenous than in bone formed on Earth. Overall, this study shows that osteocyte reshape their lacunae in response to changes, or absence, in local mechanical stimuli and different biological environments. Additionally, spatial relationships among osteocytes are complex and necessitate evaluation in carefully selected regions of interest and of large cell populations. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/474962v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@f3cc2aorg.highwire.dtl.DTLVardef@1e0fbbdorg.highwire.dtl.DTLVardef@1af3f7dorg.highwire.dtl.DTLVardef@7133b0_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗