Reviews & Analysis

By applying deep molecular profiling to our long-term mouse parabiosis model, we reveal reduced epigenetic age in old mice that shared circulation with young mice. The rejuvenation effect is sustained at two months after detachment, leading to lifespan extension and improved physical function, and is associated with rejuvenated transcriptomic signatures.

We treated aged monkeys with a dose of the longevity factor klotho, which is known to increase synaptic and cognitive functions in mice. We found that a relatively low dose of klotho enhanced cognition in aged monkeys. These findings are important because they suggest that klotho replenishment could prove to be therapeutic in aging humans.

Quantification of tau peptides in blood samples using a new mass spectrometry method suggests that individual phosphorylated tau peptides have distinct patterns of emergence in Alzheimer’s disease and differential associations with amyloid and tau pathologies. This method has the potential to stage patients along the disease continuum and for clinical trials.

We used graph neural networks trained on experimental data to identify senolytic compounds from vast chemical libraries of over 800,000 compounds and discovered structurally diverse senolytics that have potent in vitro and in vivo activity, as well as favorable medicinal chemistry properties.

Despite the central role of immune regulation in tissue repair, the contribution of immune dysfunction to regenerative failure in aging is mostly unknown. We discovered a mechanism of immune modulation that operates during skeletal muscle regeneration that is compromised in aged animals and can be harnessed to improve regenerative capacity in aging.

Clinical predictors of type 2 diabetes can be improved by considering blood-based DNA methylation scores. We derive the scores in 9,835 Scottish individuals and then test their performance against clinical predictors in 4,778 additional Scottish volunteers and 1,451 German volunteers.

We characterized the enterotypes of a large cohort of individuals of 20–117 years of age and found that the gut microbiome of centenarians has features that are usually associated with gut microbiomes of young individuals: dominance of Bacteroides spp., increase in species evenness, enrichment of potentially beneficial Bacteroidetes and depletion of potential pathobionts.

Moderately cold temperatures trigger the removal of aggregation-prone proteins in the invertebrate model Caenorhabditis elegans and cultured human cells, preventing the accumulation of pathological aggregates linked with age-related neurodegenerative disorders such as amyotrophic lateral sclerosis and Huntington’s disease.

We found evolutionarily conserved astrocyte and microglia subpopulations shared across multiple brain regions. We reveal similarities and differences between Alzheimer’s disease glia and Parkinson’s disease glia, as well as regional variance linked to disease pathology and neurodegeneration.

Cellular senesence is believed to be a driver of aging. We designed and synthesized a photosensitive prodrug that destroys senescent cells by integrating multiple technologies that combine biomarker guidance with a fluorescence tag, target-site anchoring and photodynamic therapy, providing a strategy for monitoring and specifically eliminating senescent cells to regulate aging.

Age-related decline in brain health is associated with poor blood flow and limitations in energy supply, although the vascular mechanisms are poorly understood. We report an age-related decrease in responsivity of brain microvessels, accompanied by a decrease in vessel density and loss of vascular mural cell processes.

Mitochondrial dysfunction is central in biological aging, but experimentally controlling mitochondria in vivo to test causality has been difficult. Optogenetically preserving mitochondrial function with age addressed this difficulty and increased lifespan and healthspan in Caenorhabditis elegans.

Neuroinflammation is increasingly recognized as an important pathological trigger for the development and progression of Alzheimer’s disease. However, the molecular mechanism remains largely unclear. We identify activation of the neuroimmune cGAS–STING signaling pathway as a critical molecular link, predominantly in microglia, that contributes to Alzheimer’s disease pathogenesis.

Brain functions and connectivity patterns related to maladaptive emotion regulation are poorly understood. We find that, in older adults subjected to high emotional events, functional connectivity between the default mode network and the amygdala is associated with higher anxiety, rumination and negative thoughts.

Under conditions of stress, autophagic degradation of nuclear and nucleolar components was found to promot.e youthfulness and delay aging by preserving nuclear architecture and preventing nucleolar expansion, in somatic cells. We also found that nuclear-material autophagy serves as an essential quality-control mechanism that contributes to sustaining germline immortally.

We found that aging is accompanied by a reduction in cardiomyocyte nuclear size and increased stiffness, dependent on loss of A-type lamins. Mechanistically, age-dependent nuclear remodeling represses expression of cardiogenic transcription factors that are required for heart contractility. Preserving lamin or transcription factors delays cardiac decline.

We used data from the Longitudinal Aging Study in India (LASI) to provide up-to-date epidemiological estimates of the prevalence of vision impairment among the Indian population. We find that older adults, and particularly women, marginalized groups and those from lower socioeconomic strata, had a higher prevalence of visual impairment.

Our longitudinal study comparing the skin, gut and oral microbiomes of community-dwelling older adults and nursing home residents showed striking changes known to be linked to antibiotic resistance and disease risk. Such shifts were associated with frailty, not chronological age, and were most pronounced in the skin, the primary reservoir for infection risk.

Deep learning was applied to cellular images to predict senescence on the basis of nuclear morphology. These methods recognize senescence in diverse cell types, show increasing senescence with age in liver and dermis, and suggest that higher rates of senescence associate with several age-related diseases but reduced cancer risk.

Using single-cell whole-genome sequencing, we identified and characterized the landscape of somatic single-nucleotide variants (sSNVs) in single cardiomyocytes from individuals across the human lifespan. Aged cardiomyocytes were found to have a higher burden of sSNVs and show mutational signatures that suggest failed repair of oxidative DNA damage.