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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.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

A single ultrashort pulse from X-ray free-electron laser is shown to produce a submicron, with >1,000 length-to-diameter aspect ratio long channel in solid material. The results open a new avenue for development of artificial nanofluidic devices with confinement down to the molecular level.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

The prostaglandin DP1 receptor plays critical roles in allergic responses, sleep regulation, immune modulation, and vasodilation. Here, authors present atomic structures of DP1 in different states revealing molecular mechanisms of receptor inhibition and activation.

Analyzing and integrating a broad range of behavioral phenotypes enables prediction of underlying genetic mutations in mouse models of Huntington's disease.

Pioneer of high-pressure physics and superconductivity.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Purines control intracellular energy homeostasis and nucleotide synthesis, and act as signaling molecules. Here, the authors combine structural and sequence information to define a purine-binding motif that is present in sensor domains of thousands of bacterial receptors that modulate motility, gene expression, metabolism, and second-messenger turnover.

When countries phase out coal, they compensate affected companies, communities and workers. Today more than $200 billion are allocated for such payoff, but much larger amount will be needed if China and India also phase out coal to tackle climate change.

Nuclear morphology plays a critical role in regulating gene expression and cell function. Here, Wang et al. report that topography-induced nuclear deformation enhances the secretome of hMSCs, promoting extracellular matrix (ECM) organization and facilitating bone regeneration through matricrine effects.

When strain is applied to strontium ruthenate, superconductivity emerges at a different temperature to the breaking of time-reversal symmetry. This indicates that the superconductivity could have a chiral d-wave order parameter.

Scanning SWATH increases the speed and selectivity of proteomics.

Radke et al. found an interferon response in the brainstem nuclei of acute COVID-19 that, in addition to the inflammatory reaction, spreads throughout the vascular unit altering glial cells and resolves in late disease states in the absence of brain infection.

By individually replacing 16 yeast genes encoding ABC transporters by GFP, mating and selecting for strains with accumulated mutations the authors create a Green Monster, a strain with deletions in all 16 genes.

Structures presented in this study confirm decades of genetic and biochemical evidence for the mechanism of Rho-dependent termination in bacteria.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

Gupta and colleagues use multi-omic analyses of neuroimaging and fecal metabolites to identify brain–gut–microbiome disruptions in response to discrimination that may affect preference for unhealthy eating patterns and predispose individuals experiencing discrimination-related stress to obesity.

Ovarian cancers frequently develop resistance to therapy. Here, using transcriptomics, proteomics, and preclinical models to analyse paired ascitic fluids before and after chemotherapy in ovarian cancer patients, the authors discover that extracellular secretion and spliceosomal components contribute to therapy resistance, enhancing the DNA damage response in recipient cancer cells.

Structural determination of GAT1 using cryo-electron microscopy provides insights into the biology and pharmacology of this GABA transporter.

Proteomics of small sample sizes using data-independent acquisition methods achieves higher throughput with multiplexing.

The RGS family is involved in regulating G protein signaling. Using computational analysis coupled with examination of RGS activity, a group of variable residues that together modulate G protein recognition are now identified. Mutational analysis confirmed the importance of these modulatory residues and generated gain-of-function RGS proteins. The analysis described is shown to be applicable to uncovering important residues in other protein families.

The authors identify causality-enriched CpGs linked to aging using Mendelian randomization. They develop new epigenetic clocks, DamAge and AdaptAge, that more reliably track age-related changes, offering insights into aging mechanisms and interventions.

Quantum supremacy is demonstrated using a programmable superconducting processor known as Sycamore, taking approximately 200 seconds to sample one instance of a quantum circuit a million times, which would take a state-of-the-art supercomputer around ten thousand years to compute.

Laser spectroscopy measurements of the fermium isotopic chain show a smooth trend in the nuclear size of heavy actinide elements, and diminishing shell effects on the size evolution compared with lighter nuclei.

The endoplasmic reticulum (ER) is an intracellular network characterized by highly dynamic behavior whose control mechanisms are unclear. Here, the authors show that the ER-membrane protein Reticulon (Rtnl1) can constrict ER bilayers and lead to ER fission.

A tethered macrocyclic peptide antibiotic class described here—which shows potent antibacterial activity against carbapenem-resistant Acinetobacter baumannii—blocks the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane through inhibition of the LptB₂FGC complex.

The response to checkpoint immunotherapy within bladder cancer patients is highly variable. Here, the authors use RNA-seq, ATAC-seq and digital spatial profiling of pre- and post-treatment samples from the PURE01 trial to identify subtypes associated with treatment response.

Cysteinyl leukotriene G protein-coupled receptors CysLT₁ and CysLT₂ regulate pro-inflammatory responses associated with allergic disorders. Here, authors describe four crystal structures of CysLT₂R in complex with three dual CysLT₁R/CysLT₂R antagonists, which shed light on CysLTR ligand selectivity.

Heterochronic parabiosis ameliorates age-related diseases in mice, but how it affects epigenetic aging and long-term health was not known. Here, the authors show that in mice exposure to young circulation leads to reduced epigenetic aging, an effect that persists for several months after removing the youthful circulation.

High sensitivity in quantum sensing comes often at the expense of other figures of merit, usually resulting in distortion. Here, the authors propose a protocol with good sensitivity, readout linearity and high frequency resolution, and benchmark it through signal measurements at audio bands with NV centers.

Micropillar patterns causing changes in the nuclear and cellular morphologies of human mesenchymal stromal cells influence the conformation of the cells’ chromatin and their osteogenic differentiation in vitro and in mice.

DIA-MS has emerged as a widely used technological platform for quantitative protein profiling. Here, the authors develop MSFragger-DIA, a robust and fast tool to directly identify peptides from DIA spectra. It demonstrates excellent performance across applications from large-scale tumor studies to single-cell proteomics.

There is a need for accessible ways to improve peptide spectrum match rescoring with deep learning predictions in bottom-up proteomics. Here, the authors demonstrate robust gains in peptide/protein identifications across various experiments, from single cell proteomics to immunopeptidomics.

S1P₅ is a sphingosine-1-phosphate (S1P) receptor implicated in immune and neurodegenerative disorders. Here, authors report a crystal structure of the S1P₅ receptor in complex with a selective inverse agonist, revealing an allosteric subpocket and shedding light on inverse agonism in S1P receptors.

A comprehensive transcriptomic survey of the pig could enable mechanistic understanding of tissue specialization and accelerate its use as a biomedical model. Here the authors characterize four distinct transcript types in 31 adult pig tissues to dissect their distinct structural and transcriptional features and uncover transcriptomic variability related to tissue physiology.

Methods to track molecular motion in eukaryotic cells mostly rely on fluorescent labels, transfection or photobleaching. Here the authors use multimodal partial wave spectroscopy to perform label-free live cell measurements of nanoscale structure and macromolecular motion with millisecond temporal resolution.

Riccardo Velasco and colleagues report the genome sequence of the 'Golden Delicious' domesticated apple. These data shed new insight into the genomic events that preceded the origin of this crop.

Do we mitigate climate change in a Kyoto style global agreement or via multiple agreements among smaller groups of states? Here the authors show that the best strategy may begin with regional legally binding, aggressive agreements and, as these become common, renew pursuit of a global legally-binding treaty.

The COVID-19 epidemic began later in Russia than many European countries, possibly due to restrictions on travel from China. Here, the authors analyze whole genome sequences sampled early in the epidemic in Russia, and find that most strains were not linked to China.

Cryo-electron microscopy structures of apo, agonist- and positive allosteric modulator-bound forms of the GB1–GB2 heterodimer of the metabotropic γ-aminobutyric acid (GABA) receptor shed light on the activation mechanism of this receptor.

Dietary restriction of the amino acid methionine extends the lifespan of rodents. Here the authors systematically test diets with varying amino-acid content and show that methionine restriction extends the lifespan of yeast and flies only when the content of other amino acids in the diet is also low.

It is hoped that quantum computers may be faster than classical ones at solving optimization problems. Here the authors implement a quantum optimization algorithm over 23 qubits but find more limited performance when an optimization problem structure does not match the underlying hardware.