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As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Observed 730 Myr after the Big Bang, a little red dot is found to anchor an overdensity of eight galaxies and seems to be embedded in a massive host dark matter halo.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Using JWST, more than 40 individual stars have been detected in a distant galaxy, dating back to when the Universe was only half of its current age. The stars appear to be red (super)giants that are magnified by factors of hundreds.

Here the authors explore dynamic connectivity associated with rumination in a large adolescent cohort, revealing that adult models do not generalize, while exploratory analyses suggest that variability in default-mode network connections may predict rumination, highlighting challenges in understanding depression risk factors.

This Registered Report presents evidence from 87 countries and regions showing that brief emotion-regulation interventions consistently reduced negative emotions and increased positive emotions during the COVID-19 pandemic.

In a phase 1 dose-escalation study including 11 patients with heart failure who were followed for 12 months, delivery of a cardiotropic adeno-associated viral vector designed to deliver constitutively active protein phosphatase 1 inhibitor 1 to the heart was well tolerated and showed preliminary evidence of efficacy.

Two high-redshift post-starburst galaxies are in the process of quenching, although their quasars remain active, indicating the complex co-evolution between black hole activity and star formation.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

RUBIES-EGS-QG-1 is an exceptionally massive and mature galaxy discovered just 1.2 billion years after the Big Bang. Its stars formed in an extremely rapid burst, posing a major challenge to all current theoretical models.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

A series of early-time, multiwavelength observations of an optical transient, AT2022cmc, indicate that it is a relativistic jet from a tidal disruption event originating from a supermassive black hole.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Examination of immunological changes in transgender individuals undergoing gender-affirming testosterone treatment reveals sex hormone-regulated pathways in humans and explains sex-divergent responses in cisgender individuals.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

As part of the JWST Advanced Deep Extragalactic Survey (JADES), NIRSpec has spectroscopically confirmed four young and metal-poor galaxies at redshift 10.3–13.2, from an early epoch of galaxy formation.

Low stellar ultraviolet (UV) radiation leads to low ozone abundances, therefore, less planetary UV protection. Here, the authors show that planets in the habitable zones of metal-poor stars, despite their higher UV radiation than metal-rich stars, are the best targets for search for life.

Evidence is found for a distant galaxy growing inside-out within the first 700 million years of the Universe. The galaxy has a dense central core comparable in mass density to local massive ellipticals, and an extended star-forming disc.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Genome-wide analyses of vaccine antibody responses in 2,499 infants from Uganda, South Africa and Burkina Faso identify associations between specific HLA genes and response to eight vaccines, providing insights that could be considered for population-adjusted vaccine design strategies.

An (ultraviolet) dust attenuation feature at 2,175 Å, attributed to carbonaceous dust grains in the Milky Way and nearby galaxies, also exists in galaxies up to a redshift of 7.

The discovery of a distant blazar J0410−0139 at z = 7 suggests that many similar sources existed in the early Universe, supporting the hypothesis that the rapid growth of black holes is driven by jet-enhanced or obscured accretion.

Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Anecdotal reports suggest potential severity and outcome differences between sexes following infection by SARS-CoV-2. Here, the authors perform meta-analyses of more than 3 million cases collected from global public data to demonstrate that male patients with COVID-19 are 3 times more likely to require intensive care, and have ~40% higher death rate.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Sottoriva and colleagues combine next-generation sequencing and AI-aided histopathology to assess tumor evolvability in patient samples with long-term follow-up and find that it can be a strong predictor of recurrence in high-risk prostate cancer.

The nature of young star clusters in the Magellanic Clouds is debated. Here, the authors show an alternative approach that exploits data to exclude the presence of age differences greater than a few million years among cluster stars in a very young cluster.

Patients with metastatic cancers of unknown primary (CUP) are currently unable to gain access to drugs through standard of care or clinical trials. Here, the authors perform whole-genome and transcriptome sequencing (WGTS) on 72 patients with CUP and demonstrate the feasibility of using WGTS to determine the specific cancer types of CUP, thereby clinically benefiting patients with CUP.

Liver X receptor drives epithelial Areg-mediated intestinal regeneration, while preventing tumour growth through adaptive immune responses.

In this study, the authors document how SIRPα, a cell-adhesion molecule, participates in the late maturation of hippocampal excitatory synapses. They find that in response to activity, SIRPα sheds its ectodomain, which acts presynaptically to promote maturation in a process that requires CaM kinase, matrix metalloproteinases and the presynaptic receptor CD47.

Investigation of the physical conditions of the circumgalactic medium led to detection of two compact [C ii]-emitting galaxies with narrow linewidths at a redshift of 5.7, associated with a complex, high-ionization C iv absorption system.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.