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APOE loss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer's disease pathology
The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Knockdown of ε4 may provide a therapeutic strategy for AD, but the effect of APOE loss of function (LoF) on AD pathogenesis is unknown. We searched for APOE LoF variants in a large cohort of controls and patients with AD and identified seven heterozygote carriers of APOE LoF variants. Five carriers were controls (aged 71-90 years), one carrier was affected by progressive...
An atlas of cells in the human tonsil
Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an...
Tissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans
Ageing exhibits common and distinct features in various tissues, making it critical to decipher the tissue-specific ageing mechanisms. MiRNAs are essential regulators in ageing and are recently highlighted as a class of intercellular messengers. However, little is known about the tissue-specific transcriptomic changes of miRNAs during ageing. C. elegans is a well-established model organism in ageing research. Here, we profile the age-dependent miRNAomic changes in five isolated worm tissues....
Brain asymmetries from mid- to late life and hemispheric brain age
The human brain demonstrates structural and functional asymmetries which have implications for ageing and mental and neurological disease development. We used a set of magnetic resonance imaging (MRI) metrics derived from structural and diffusion MRI data in N=48,040 UK Biobank participants to evaluate age-related differences in brain asymmetry. Most regional grey and white matter metrics presented asymmetry, which were higher later in life. Informed by these results, we conducted hemispheric...
The use of a systems approach to increase NAD<sup>+</sup> in human participants
Reversal or mitigation against an age-related decline in NAD^(+) has likely benefits, and this premise has driven academic and commercial endeavour to develop dietary supplements that achieve this outcome. We used a systems-based approach to improve on current supplements by targeting multiple points in the NAD^(+) salvage pathway. In a double-blind, randomised, crossover trial, the supplement - Nuchido TIME+® (NT) - increased NAD^(+) concentration in whole blood. This was associated with an...
Human myofiber-enriched aging-induced lncRNA FRAIL1 promotes loss of skeletal muscle function
The loss of skeletal muscle mass during aging is a significant health concern linked to adverse outcomes in older individuals. Understanding the molecular basis of age-related muscle loss is crucial for developing strategies to combat this debilitating condition. Long noncoding RNAs (lncRNAs) are a largely uncharacterized class of biomolecules that have been implicated in cellular homeostasis and dysfunction across a many tissues and cell types. To identify lncRNAs that might contribute to...
Daily briefing: Discoveries from a huge study of mothers and babies in China
Why autoimmune disease is more common in women: X chromosome holds clues
This AI learnt language by seeing the world through a baby’s eyes
In the AI science boom, beware: your results are only as good as your data
How to enhance lab-team efficiency with tools from the tech industry
Racing extinction: Can science act fast enough to save large, endangered mammals?
Science, Volume 383, Issue 6682, February 2024.
Passion, curiosity and perseverance: my mission to capture women in science on camera
Number of Black UK professors rises by 25% in one year
Publisher Correction: Developmental dynamics of two bipotent thymic epithelial progenitor types
In Science Journals
Science, Volume 383, Issue 6682, Page 491-493, February 2024.
Sustainability limits needed for CO2 removal
Science, Volume 383, Issue 6682, Page 484-486, February 2024.
New Products
Science, Volume 383, Issue 6682, Page 559-559, February 2024.
Earning respect and trust
Science, Volume 383, Issue 6682, Page 463-463, February 2024.
News at a glance
Science, Volume 383, Issue 6682, Page 464-465, February 2024.