In this issue, HaiYang Wang et al. show that oocytes from aged mice cultured within follicles from young mice improve their developmental potential. The cover shows reconstituted chimeric follicles in which granulosa cells interact with the oocyte through transzonal projections.

See Wang et al.

In this issue, Mei Tao, Jiani Chen, Chunlai Cui, Yandong Xu et al. analyze the co-evolution of mitochondrial and nuclear genomes in 472 insects and identify a group of non-mitochondria-targeted nuclear genes that potentially co-function with mtOXPHOS genes. Their discovery includes the uncharacterized gene CG11837 — a putative ortholog of human DIMT1 — that regulates insect lifespan. The cover image shows a collection of insect species, illustrating the diversity of animals in this class that contributed to this study.

See Tao et al.

In this issue, Shihong Max Gao et al. use a model organism that has been fundamental to our understanding of aging biology — Caenorhabditis elegans — and generate a comprehensive single-cell transcriptome atlas, profiling the cell-type-specific effects of aging and pro-longevity strategies. The cover image portrays two intertwined worms transitioning into swirling particles that stretch through time, assembling into a radial graph.

See Gao et al.

In this issue, three studies examine the contribution of stochastic epigenetic changes to DNA methylation clocks. Tarkhov et al., Meyer et al. and Tong et al. take different approaches to addressing this question, and concur that stochasticity is involved in epigenetic aging. The cover, from Meyer et al., shows a Galton board, which is a device used to illustrate concepts of probability and stochasticity. At the top, a series of small balls are released, which follow a random path before landing in bins at the bottom. Over many trials, this stochastic process leads to the formation of a normal distributed shape. A clock is depicted within this shape to illustrate that a completely stochastic process can be used to construct aging clocks, consistent with a role of age-dependent increases in stochastic variation in epigenetic processes.

See Tarkhov et al., Meyer et al. & Tong et al.

In this issue, two studies comprehensively describe the lipidome during aging in mice. Janssens et al. report that bis(monoacylglycero)phosphate (BMP) accumulates during mouse aging, and that this lipid also accumulates in muscle in older humans and reduces upon a short bout of exercise. Tsugawa et al. profile the lipidome in 13 tissues and 4 ages of mice, taking into account sex and microbiome dependencies. Among many findings, they report that polyunsaturated fatty acid-containing BMP increases in various organs during aging. The cover shows a pocket watch being pushed by two older people. The numbers on the face of the clock are BMP molecules, which become larger in size to reflect their increased abundance with age. Pushing the clock denotes that BMP levels can be modified by exercise.

See Janssens et al. & Tsugawa et al.

In this issue, Pingze Zhang et al. reveal that S6K suppression in the fruit-fly fat body mediates the longevity effects of rapamycin, and uncover a sex-dimorphic link through to lysosome morphology and inflammation, via Syntaxin 13. The cover image conceptualizes the link to inflammaging by depicting aged flies as confined to a jar (representing the nuclear localization of the Drosophila NFκB-like transcription factor Relish), emitting brighter light (representing upregulation of inflammatory mediators).

See Zhang et al.

In this issue, Kojiro Suda, Yohsuke Moriyama, Nurhanani Razali and colleagues set out, using a genome-wide screen and gene-expression analysis in budding yeast, to better understand the cellular response to plasma membrane damage. The team discover that damage to the plasma membrane can limit replicative lifespan in yeast and induce senescence in human fibroblasts. The cover image shows kintsugi, the traditional Japanese art of repairing broken pottery by mending the cracks with urushi and gold. Kintsugi visibly incorporates the history of an object into its new form and thus transforms it. In this analogy, cell membrane damaged is repaired; however, rather than restoring the cell to its previous form, the new cellular nature is irreversibly changed and distinct from its previous state.

See Suda et al.

In this issue, Kejun Ying et al. identify CpGs that may be causally linked to aging-related traits using epigenome-wide Mendelian randomization. They develop the epigenetic clocks DamAge and AdaptAge, which track adverse and adaptive outcomes, respectively. The cover image conceptualizes the relationship between DNA methylation and the aging process as a cascade of dominoes that links the youthful individual with the old one. Each domino represents a key CpG site with a causal influence on aging undergoing methylation (denoted by the letter ‘M’). The falling of the dominoes embodies causal effects of these methylation events, suggesting a sequential impact on the progression of aging.

See Ying et al.

In this issue, Netta Mendelson Cohen et al. investigate individuals’ trajectories of healthy aging and age-related diseases. The researchers stitch together electronic health records with partial longitudinal coverage, using machine learning to untangle future healthy aging from chronic disease, and identify early indicators for healthy longevity. The cover image shows the study’s longevity-model features superimposed with representations of electronic health record information, which are connected via multiple solid or dotted lines that indicate differing propensities to drive the outputs of the models.

See Cohen et al.