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Clonal persistence dominates homeostatic intestinal IgA responses
Immunoglobulin A (IgA) is the most abundantly produced antibody isotype and mediates protection and homeostatic regulation at mucosal surfaces. Steady-state IgA production is supported by multiple pathways, including chronic germinal centers in gut inductive lymphoid tissues. However, we lack a detailed understanding of how IgA responses are temporally integrated across inductive and effector sites. Here, we dissect homeostatic IgA responses from the perspective of clonal repertoires in...
Attenuation of ATM signaling by ROS delays replicative senescence at physiological oxygen
Replicative senescence is a powerful tumor suppressor pathway that curbs proliferation of human cells when a few critically-short telomeres activate the DNA damage response (DDR). We show that ATM is the sole DDR kinase responsible for the induction and maintenance of replicative senescence and that ATM inhibition can induce normal cell divisions in senescent cells. Compared to non-physiological atmospheric (∼20%) oxygen, primary fibroblast cells grown at physiological (3%) oxygen were more...
Epigenome-wide association study of nuclear DNA methylation in relation to mitochondrial heteroplasmy
We analyze 10,986 participants (mean age 77; 63% women; 54% non-White) across seven U.S. cohorts to study the relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA methylation. We identify 597 CpGs associated with heteroplasmy burden, generally showing lower methylation. These CpGs are enriched in dynamically regulated island shores and depleted in CpG islands, indicating involvement in context-specific rather than constitutive gene regulation. In HEK293T cells, we...
Oral functional limitation and risk of frailty onset in older adults: a sex-stratified 4-Year cohort study with competing risk analysis
CONCLUSION: Self-reported oral functional limitation was significantly associated with frailty onset over 4 years, particularly among women. Incorporating oral function assessment into geriatric screening and community health programs may facilitate early identification of risk and the implementation of preventive strategies for frailty.
DNA methylation-based epigenetic clocks highlight immune-driven aging acceleration in COVID-19 across diverse populations
The SARS-CoV-2 pandemic has affected millions worldwide, with aging being a key risk factor for severe disease outcomes. This study examines the rate of epigenetic aging, as measured by DNA methylation-based aging markers, in COVID-19 patients versus healthy individuals. We found that PCGrimAge, a next-generation epigenetic clock associated with immune dysregulation and inflammation, showed the strongest correlation with the chronological age of the European COVID-19 patients. Several other...
Mesenchymal cell-derived extracellular vesicles ameliorate age-related deficits in working memory and in vivo MRI measures of white matter structure and function in rhesus monkeys
Aging humans and non-human primates both exhibit a similar pattern of cognitive decline beginning in middle age that is characterized by progressive impairments in rule learning, executive function, and working and recognition memory-functions often associated with dysfunction of prefrontal and medial temporal lobe regions. The heterogeneity and inter-subject variability in aging and age-related cognitive impairments present challenges for developing effective therapeutics and can be attributed...