Biology subjects

Kothari, M.

Publications and source records attributed to Kothari, M..

2 recordsLinked to original sources

bioRxiv2021

Social mobility and biological aging among older adults in the United States

Lower socioeconomic status is associated with faster biological aging, the gradual and progressive decline in system integrity that accumulates with advancing age. Efforts to promote upward social mobility may therefore extend healthy lifespan. However, recent studies suggest that upward mobility may also have biological costs related to the stresses of crossing social boundaries. We analyzed blood-chemistry and DNA methylation (DNAm) data from n=9286 participants in the 2016 Health and Retirement Study (HRS) Venous Blood Study to test associations of life-course social mobility with biological aging. We quantified social mobility from childhood to later-life using data on childhood family characteristics, educational attainment, and wealth accumulation. We quantified biological aging using three DNA methylation "clocks" and three blood-chemistry algorithms. We observed substantial social mobility among study participants. Those who achieved upward mobility exhibited less-advanced and slower biological aging. Associations of upward mobility with less-advanced and slower aging were consistent for blood-chemistry and DNAm measures of biological aging and were similar for men and women and for Black and White Americans (Pearson-r effect-sizes ~0.2 for blood-chemistry measures and the DNAm GrimAge clock and DunedinPoAm pace-of-aging measures; effect-sizes were smaller for the DNAm PhenoAge clock). Analysis restricted to educational mobility revealed differential effects by racial identity, suggesting that mediating links between educational mobility and healthy aging may be disrupted by structural racism. In contrast, mobility producing accumulation of wealth appeared to benefit White and Black Americans equally, suggesting economic intervention to reduce wealth inequality may have potential to heal disparities in healthy aging. Significance StatementUpward social mobility may disrupt effects of early-life disadvantage on aging-related health decline. However, the stresses of crossing social boundaries can have biological costs. To investigate the balance of these forces, we analyzed social mobility from reports of childhood circumstances, education, and later-life wealth in 9,286 older adults in the US Health and Retirement Study. We quantified life-course health impacts of social mobility from blood-chemistry and DNA-methylation analysis of biological aging. We found that educational mobility alone benefited Black Americans less than White Americans, whereas mobility that produced accumulation of wealth into later-life was associated with delayed biological aging across social categories. Black-White disparities in healthy-aging outcomes of educational mobility may reflect inequalities in social gains realized from education.

physiology↗

bioRxiv2021

Mechanical stress determines morphogenesis and cell ordering in confined bacterial biofilms

Biofilms are aggregates of bacterial cells surrounded by an extracellular matrix. Much progress has been made in studying biofilm growth on solid substrates; however, little is known about the biophysical mechanisms underlying biofilm development in three-dimensional confined environments, in which the biofilm-dwelling cells must push against and even damage the surrounding environment to proliferate. Here, combining single-cell imaging, mutagenesis, and rheological measurement, we reveal the key morphogenesis steps of Vibrio cholerae biofilms embedded in hydrogels as they grow by four orders of magnitude from their initial size. We show that the morphodynamics and cell ordering in embedded biofilms are fundamentally different from those of biofilms on flat surfaces. Treating embedded biofilms as inclusions growing in an elastic medium, we quantitatively show that the stiffness contrast between the biofilm and its environment determines biofilm morphology and internal architecture, selecting between spherical biofilms with no cell ordering and oblate ellipsoidal biofilms with high cell ordering. When embedded in stiff gels, cells self-organize into a bipolar structure that resembles the molecular ordering in nematic liquid crystal droplets. In vitro biomechanical analysis shows that cell ordering arises from stress transmission across the biofilm-environment interface, mediated by specific matrix components. Our imaging technique and theoretical approach are generalizable to other biofilm-forming species, and potentially to biofilms embedded in mucus or host tissues as during infection. Our results open an avenue to understand how confined cell communities grow by means of a compromise between their inherent developmental program and the mechanical constraints imposed by the environment. Significance StatementBiofilms are microbial cities in which bacterial cells reside in a polymeric matrix. They are commonly found inside soft confining environments such as food matrices and host tissues, against which bacteria must push to proliferate. Here, by combining single-cell live imaging and mechanical characterization, we show that the confining environment determines the dynamics of biofilm shape and internal structure. This self-organized evolution of biofilm architecture is caused by force transmission between the environment and the biofilm, mediated by the extracellular matrix secreted by the cells. Our findings lead to new ways to understand how bacterial communities develop under mechanical constraints, and potentially to new strategies for preventing and controlling biofilm growth in three-dimensional environments.

microbiology↗