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Transposable elements (TEs) in the human genome are the heritage of ancient parasitic infections. While most of human DNA comprises TEs and TE-derived elements, their repetitive nature poses technical challenges; thus, little is known about their positional identity and regulatory roles. Here, by integrating long-read and multidimensional transcriptional analyses, we investigate when, where and how TEs become part of a gene. We characterize how TE-derived isoforms change across mouse-human...

Biological aging reflects complex cellular and biochemical processes that can be measured across multiple omic layers. Using routine clinical laboratory data from ~31,000 participants in the Mass General Brigham Biobank, we developed EMRAge, a biomarker of mortality risk that can be broadly recapitulated across electronic medical records. Here we show that EMRAge can be modeled using elastic net regression with DNA methylation and multi-omics to generate DNAmEMRAge and OMICmAge, respectively....

Neuroplasticity, the brain's capacity to adapt and reorganize in response to experiences and environmental changes, is fundamental to cognitive aging. As individuals age, cognitive functions such as memory, processing speed, and executive function commonly decline, driven largely by changes in neuroplasticity mechanisms like synaptic plasticity, neurogenesis, and functional reorganization. Synaptic plasticity is a well-established mechanism supporting learning and memory across the lifespan,...

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The misfolding and accumulating α-synuclein (αSyn) is a central pathological hallmark of various neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Under physiological conditions, αSyn essential for normal synaptic functions primarily through its regulation of synaptic vesicle trafficking, clustering, and neurotransmitter release. However, in disease states, the accumulation of pathological αSyn disrupts intracellular proteostasis,...

The existence of human hippocampal neurogenesis has long been disputed^(1-12) and its relevance in cognition remains unknown. Recent studies have established the presence of proliferating progenitors and immature neurons and a reduction in the latter in Alzheimer's disease (AD)^(11,13). However, their origin and the molecular networks that regulate neurogenesis and function are poorly understood. Here we studied human post-mortem hippocampi obtained from different cohorts: young adults with...

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Increased life expectancy brought about by improved healthcare and lifestyle has heightened the challenge of neurodegenerative disorders like Alzheimer's disease (AD) and other age-related disorders. Neurodegeneration is known to be accompanied by loss of memory, changes in brain morphology, and neuroinflammation, and multiple factors contribute to the progression and pathogenesis of the condition. Of these factors, metabolic dysregulation is known to influence the process, but the precise...

Increased life expectancy brought about by improved healthcare and lifestyle has heightened the challenge of neurodegenerative disorders like Alzheimer's disease (AD) and other age-related disorders. Neurodegeneration is known to be accompanied by loss of memory, changes in brain morphology, and neuroinflammation, and multiple factors contribute to the progression and pathogenesis of the condition. Of these factors, metabolic dysregulation is known to influence the process, but the precise...

To investigate the relevance of small RNAs to human longevity, we pursued three goals: (a) to validate epigenetic (small RNA) factors underlying survival of older adults, (b) to develop and validate prediction models of survival for potential clinical application, and (c) to identify plausible druggable targets prolonging longevity. We evaluated 828 small non-coding RNAs-687 microRNAs (miRNAs) and 141 piwi-interacting RNAs (piRNAs)-in baseline plasma from 1271 community-dwelling older adults (≥...

Researchers worry question plus other changes will reduce accuracy and boost costs of 2030 count