Proteomics-based aging clocks in midlife and late-life and risk of dementia.

Biological age can be quantified by composite proteomic scores, called aging clocks. We investigated whether biological age acceleration (a discrepancy between chronological and biological age) in midlife and late-life is associated with cognitive function and risk of dementia. We used two population-based cohort studies: Atherosclerosis Risk in Communities (ARIC) Study and Multi-Ethnic Study of Atherosclerosis (MESA).

TET2-loss enhances immediate and time-resolved IFNγ signaling responses across myeloid differentiation.

Signaling responses to cytokines are disrupted in clonal hematopoiesis and myeloid malignancies. To better identify specific signaling response alterations in the presence or absence of TET2, we developed a 36-parameter CyTOF panel of both surface marker and phosphoprotein antigens in murine BM. We show diverse, cell-type specific inflammatory cytokine responses in healthy hematopoietic cells.

The Association between Proteomic Aging Clocks and the Risk of Cancer in Midlife Individuals.

Background: To measure the aging process before a cancer diagnosis, we developed the first cancer-specific proteomic aging clock (CaPAC) and examined its association with cancer risk in the Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis (MESA) studies.

Methods: Using the SomaScan assay, ARIC measured 4,712 proteins in plasma samples collected in 1990-92 from 3,347 participants who developed cancer over follow-up until 2015 and 7,487 who remained cancer-free, all aged 46-70. We constructed CaPAC0 using elastic net regression among two-thirds randomly selected cancer-free participants (N=4,991, training set) and calculated age acceleration for CaPAC0 (CaPAA0) as residuals of CaPAC0 on chronological age in all remaining ARIC participants.

Ultrarare Variants in DNA Damage Repair Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome or Acute Behavioral Regression in Neurodevelopmental Disorders.

Introduction: Acute onset of severe psychiatric symptoms or regression may occur in children with premorbid neurodevelopmental disorders, although typically developing children can also be affected. Infections or other stressors are likely triggers. The underlying causes are unclear, but a current hypothesis suggests the convergence of genes that influence neuronal and immunological function.

Glucagon-like peptide-1 receptor agonist-based agents and weight loss composition: Filling the gaps.

Excess adiposity is at the root of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as first-line treatments for T2D based on significant weight loss results. The composition of weight loss using most diets consists of <25% fat-free mass (FFM) loss, with the remainder from fat stores.