AAV-mediated knockdown of LCN2 in aged mice limited microglial inflammation, reduced neuronal pyroptosis, and rescued memory following surgery.AAV-mediated knockdown of LCN2 in aged mice limited microglial inflammation, reduced neuronal pyroptosis, and rescued memory following surgery. In aged C57BL/6J mice, surgical stress from a unilateral nephrectomy triggered cognitive impairment alongside elevated hippocampal TLR3, LCN2, and…
Genomes from 248 Alzheimer's patients carried significantly more endogenous viral elements than those from 240 cognitively healthy centenarians…Genomes from 248 Alzheimer's patients carried significantly more endogenous viral elements than those from 240 cognitively healthy centenarians (p=3.2x10-4). In a preprint analyzing long-read sequencing data from 248 human Alzheimer's disease patients and 240 cognitively healthy…
Genetically higher SHBG increased lumbar fracture risk with an odds ratio of 1.201 in FinnGen and 1.005 in UK Biobank, mediated primarily by bone…Genetically higher SHBG increased lumbar fracture risk with an odds ratio of 1.201 in FinnGen and 1.005 in UK Biobank, mediated primarily by bone density. In human genome-wide association datasets from FinnGen, the UK Biobank, and IEU OpenGWAS, researchers used a two-sample bidirectional…
In 198 adults aged 40 to 65, larger brainstem volume tied to better memory, with the strongest link seen in participants with elevated arterial…In 198 adults aged 40 to 65, larger brainstem volume tied to better memory, with the strongest link seen in participants with elevated arterial stiffness. In a study of 198 healthy adults aged 40 to 65 years, researchers tested whether brainstem volume relates to cognitive function and…
Across 13 traits tracked over four decades in wild Seychelles warblers, only five showed age-related declines, with no evidence of synchronized aging…Across 13 traits tracked over four decades in wild Seychelles warblers, only five showed age-related declines, with no evidence of synchronized aging among them. In a wild population of Seychelles warblers (Acrocephalus sechellensis), researchers tracked 13 reproductive, behavioral…
In 3-month-old and 18-month-old mice with experimental stroke, aged animals failed to regain somatomotor functional connectivity and behavioral…In 3-month-old and 18-month-old mice with experimental stroke, aged animals failed to regain somatomotor functional connectivity and behavioral performance. In mice, researchers used wide-field calcium imaging to examine cortical network dynamics and behavioral recovery following stroke.
Two human cohorts of 973 and 129 individuals revealed that aging and Alzheimer's disease disrupt separate, orthogonal functional communication axes…Two human cohorts of 973 and 129 individuals revealed that aging and Alzheimer's disease disrupt separate, orthogonal functional communication axes across the brain. In two independent human cohorts (BioFINDER-2, N = 973; Alzheimer's Disease Neuroimaging Initiative, N = 129), researchers…
The Journal of Pharmacology and Experimental TherapeuticsAnimals·
In ovariectomized rats, inhibiting TRPM3 with naringenin restored serotonin signaling and dendritic arborization while reducing neuroinflammation and…In ovariectomized rats, inhibiting TRPM3 with naringenin restored serotonin signaling and dendritic arborization while reducing neuroinflammation and depressive-like deficits.
In 510 older adults, higher performance variability tracked lower anisotropy in specific tracts, with an effect size of 0.09 across 7.57% of…In 510 older adults, higher performance variability tracked lower anisotropy in specific tracts, with an effect size of 0.09 across 7.57% of whole-brain tract volume. Participants were 510 community-dwelling older adults from the Health and Aging Brain Study-Health Disparities cohort, with…
In a Swedish cohort, 5-ARI users had a 17% lower risk of laryngeal or hypopharyngeal squamous cell carcinoma than nonusers (adjusted hazard ratio…In a Swedish cohort, 5-ARI users had a 17% lower risk of laryngeal or hypopharyngeal squamous cell carcinoma than nonusers (adjusted hazard ratio, 0.83). In a cohort study of Swedish men, researchers investigated whether 5α-reductase inhibitors (5-ARIs) were associated with a lower risk of…
In 6,531 adults, waist-to-height ratio mediated 44% and interleukin-6 mediated 13% of the association between ultraprocessed food intake and incident…In 6,531 adults, waist-to-height ratio mediated 44% and interleukin-6 mediated 13% of the association between ultraprocessed food intake and incident cardiovascular disease. In a prospective cohort of 6,531 men and women aged 45 to 84 years from the Multi-Ethnic Study of Atherosclerosis…
A Mendelian randomization analysis found total cholesterol mediated 93.91% of statins' effect on overall dementia and 84.37% on dementia in…A Mendelian randomization analysis found total cholesterol mediated 93.91% of statins' effect on overall dementia and 84.37% on dementia in Alzheimer's disease. In humans, researchers analyzed genome-wide association study summary data using Mendelian randomization to evaluate causal links…
In a preprint analyzing epigenome-wide data from thousands of U.S. veterans, posttraumatic stress disorder was significantly associated with…In a preprint analyzing epigenome-wide data from thousands of U.S. veterans, posttraumatic stress disorder was significantly associated with accelerated DNA methylation aging. In a preprint study of U.S.
In 279 older adults at risk for Alzheimer's disease, longitudinal changes in brain network control energy tracked cognitive performance and plasma…In 279 older adults at risk for Alzheimer's disease, longitudinal changes in brain network control energy tracked cognitive performance and plasma p-tau181 levels. In a preprint study of 279 older adults at familial risk for Alzheimer's disease, researchers examined longitudinal shifts in…
Single-cell analysis of four aged human donor eyes revealed complement membrane attack complexes concentrated primarily on pericytes, smooth muscle…Single-cell analysis of four aged human donor eyes revealed complement membrane attack complexes concentrated primarily on pericytes, smooth muscle cells, and macrophages. In tissue from four aged human donor eyes, researchers profiled surface complement proteins alongside transcriptomes…
Global and rod-specific knockout mice developed rhodopsin mislocalization and progressive scotopic vision loss starting at six months of age.Global and rod-specific knockout mice developed rhodopsin mislocalization and progressive scotopic vision loss starting at six months of age. In mice and human cell cultures, researchers examined how the motor protein MYO1C controls rhodopsin trafficking and retinal health.
In a study of App SAA knock-in mice from 4 to 19 months, animals developed progressive amyloid pathology, neuroinflammation, biomarker shifts, and…In a study of App SAA knock-in mice from 4 to 19 months, animals developed progressive amyloid pathology, neuroinflammation, biomarker shifts, and synaptic loss. In homozygous App SAA knock-in mice evaluated from 4 to 19 months of age, researchers observed progressive, age-dependent…
In 12-month-old Col4a2 mutant mice, cerebral pial arteries showed impaired myogenic tone driven by PKA-dependent remodeling of ryanodine receptor…In 12-month-old Col4a2 mutant mice, cerebral pial arteries showed impaired myogenic tone driven by PKA-dependent remodeling of ryanodine receptor clusters. In heterozygous Col4a2+/G646D mice, researchers investigated how a collagen mutation linked to cerebral small vessel disease affects…
Human neural, cardiac, and tonsil organoids exposed to 24 hours of simulated microgravity showed tissue-specific changes, including higher…Human neural, cardiac, and tonsil organoids exposed to 24 hours of simulated microgravity showed tissue-specific changes, including higher transcriptomic-age estimates in brain and heart models.
Multi-omics profiling in Drosophila links chromatin regulation to increased ATP, higher NAD-to-NADH ratios, and altered lipid metabolism in aged…Multi-omics profiling in Drosophila links chromatin regulation to increased ATP, higher NAD-to-NADH ratios, and altered lipid metabolism in aged heads. In aged male fruit flies (Drosophila), pan-neuronal suppression of dENL/AF9 drives a distinct metabolic and energetic signature.
Tracking over 500 marine bryozoans in the field showed that larval energetic stress lowered lifetime reproductive success but reduced the rate of…Tracking over 500 marine bryozoans in the field showed that larval energetic stress lowered lifetime reproductive success but reduced the rate of actuarial senescence. In the colonial marine bryozoan Bugula neritina, researchers manipulated early-life stress by experimentally extending the…
In mice challenged with bacteria or sensitization, local fluid profiling revealed age-altered immune cell recruitment despite preserved overall…In mice challenged with bacteria or sensitization, local fluid profiling revealed age-altered immune cell recruitment despite preserved overall transcriptional responses to infection.
Corticosterone treatment shifts DNA methylation profiles in young chicks toward those of older birds and reshapes longevity pathways.Corticosterone treatment shifts DNA methylation profiles in young chicks toward those of older birds and reshapes longevity pathways. In zebra finch chicks (Taeniopygia guttata), experimental early-life stress accelerates epigenetic aging, according to a new preprint.
A new preprint shows tamoxifen-inducible mouse models remain valid for ovarian aging research despite transient disruptions to estrous cycling.A new preprint shows tamoxifen-inducible mouse models remain valid for ovarian aging research despite transient disruptions to estrous cycling. Female mice treated with tamoxifen show transient reproductive disruptions but normal long-term ovarian aging, according to a recent preprint.
Loss of the cGAMP-degrading enzyme ENPP1 allows microglia-derived signaling molecules to trigger STING-dependent inflammation across multiple brain…Loss of the cGAMP-degrading enzyme ENPP1 allows microglia-derived signaling molecules to trigger STING-dependent inflammation across multiple brain cell types. In a mouse study, researchers found that advanced age and experimental autoimmune encephalomyelitis cause microglia to accumulate…
Aged male mice showed far larger proteomic shifts than females following microglial removal, including alterations in synaptic and mitochondrial…Aged male mice showed far larger proteomic shifts than females following microglial removal, including alterations in synaptic and mitochondrial proteins. In a new preprint, researchers depleted microglia in 21-month-old male and female mice using the CSF1R inhibitor PLX5622 to evaluate…
Researchers identified a conserved neural progenitor pool that drives weekly brain regeneration in Botryllus schlosseri but collapses during aging.Researchers identified a conserved neural progenitor pool that drives weekly brain regeneration in Botryllus schlosseri but collapses during aging. In the colonial chordate Botryllus schlosseri, the entire central nervous system resorbs and regenerates de novo each week.
At seven days of recovery from disuse, older women exhibited 7,999 differentially expressed genes across muscle cell types compared to 1,548 in…At seven days of recovery from disuse, older women exhibited 7,999 differentially expressed genes across muscle cell types compared to 1,548 in younger women. In a preprint, researchers analyzed skeletal muscle and primary cells from eight young women (aged 22±3 years) and nine older women…
Processed SCAF1 halts mitochondrial ribosome assembly and induces senescence in human cell models following peroxisome import stress.Processed SCAF1 halts mitochondrial ribosome assembly and induces senescence in human cell models following peroxisome import stress. In a preprint using cultured human cells, researchers uncovered a signaling pathway connecting peroxisome stress directly to mitochondrial dysfunction and…
Profiling lysosomal fractions from mouse cortex from 3 to 24 months revealed an accumulation of myelin-derived glycosphingolipids that was most…Profiling lysosomal fractions from mouse cortex from 3 to 24 months revealed an accumulation of myelin-derived glycosphingolipids that was most pronounced in microglia. In mice, aging lysosomes in the cerebral cortex accumulate myelin lipids and proteins as sphingolipid breakdown shifts.
Spatial transcriptomics shows neuronal and vascular DNA damage responses correspond to distinct local cell neighborhoods in aging brains.Spatial transcriptomics shows neuronal and vascular DNA damage responses correspond to distinct local cell neighborhoods in aging brains. In this preprint, researchers studied brain tissue from 2- to 3-month-old and 22-month-old mice to investigate how DNA repair relates to tissue…
Researchers identified a transient senescent-like monocyte state governed by the transcription factor AP-1 that primes cells toward inflammatory and…Researchers identified a transient senescent-like monocyte state governed by the transcription factor AP-1 that primes cells toward inflammatory and sepsis-associated states. In aging humans, dysfunctional monocyte states contribute to systemic inflammation, but the underlying regulatory…
Targeting senescent immune cells with fisetin or ruxolitinib reduced disease features and protected mice against autoimmune peripheral nerve damage.Targeting senescent immune cells with fisetin or ruxolitinib reduced disease features and protected mice against autoimmune peripheral nerve damage. In human patients with chronic inflammatory demyelinating polyneuropathy and in mice with CIDP-like disease, researchers found elevated…
Human neurons from frontotemporal lobar degeneration patients showed ultra-low-frequency TARDBP variants that were less abundant in individuals who…Human neurons from frontotemporal lobar degeneration patients showed ultra-low-frequency TARDBP variants that were less abundant in individuals who died at older ages. In a preprint analyzing postmortem human brain tissue, researchers sequenced 39,800 neurons from 52 individuals with…
Deleting Vegfa in CX3CR1-positive macrophages raised intraocular pressure and reduced aqueous humor outflow facility in nine-month-old mice.Deleting Vegfa in CX3CR1-positive macrophages raised intraocular pressure and reduced aqueous humor outflow facility in nine-month-old mice. In mice and human tissue imaging, aging was associated with reduced Schlemm's canal size and increased macrophage accumulation around the canal.
Diminished SATB1 in murine naive CD4⁺ T cells weakens TAD boundaries, rewires enhancer-promoter interactions, and increases proinflammatory gene…Diminished SATB1 in murine naive CD4⁺ T cells weakens TAD boundaries, rewires enhancer-promoter interactions, and increases proinflammatory gene expression during aging. In mice, aging reshapes chromatin architecture and transcriptional regulation in naive CD4⁺ T cells, according to a new…
In cultured fibroblasts and mice, apolipoprotein D triggers SUN1 accumulation, reinforcing a signaling cycle that alters gene expression and cellular…In cultured fibroblasts and mice, apolipoprotein D triggers SUN1 accumulation, reinforcing a signaling cycle that alters gene expression and cellular polarity. In cultured fibroblasts and mice, researchers examined how aging cells spread phenotypes to nearby cells, according to a new…
Male mice experience greater distal axon withdrawal that can be reversed by targeting muscle niches with nerve growth factor.Male mice experience greater distal axon withdrawal that can be reversed by targeting muscle niches with nerve growth factor. In a new preprint, researchers investigated sympathetic innervation in mouse skin across aging.
Age-related gut stiffening activates smooth muscle Piezo1, triggering calcium signaling that suppresses contractile genes and slows intestinal…Age-related gut stiffening activates smooth muscle Piezo1, triggering calcium signaling that suppresses contractile genes and slows intestinal transit. In mice, aging slows whole gut and colonic transit, increases regional stiffness, and reduces smooth muscle contractility, according to a…
The microRNA inhibitor also improved cardiac outcomes after infarction and reduced pathology in mouse and pig models of muscular dystrophy.The microRNA inhibitor also improved cardiac outcomes after infarction and reduced pathology in mouse and pig models of muscular dystrophy. In aged mice, inhibiting the microRNA miR-128-3p with antisense oligonucleotides restored muscle mass and function, according to a recent preprint.
A large genomic analysis reveals over 800 inherited variants and structural features that alter how frequently chromosomes missegregate in aging…A large genomic analysis reveals over 800 inherited variants and structural features that alter how frequently chromosomes missegregate in aging individuals. In a preprint analyzing blood whole-genome sequencing from 840,853 humans, researchers investigated how inherited genetics shapes…
Cortical neurons gain mutations at similar yearly rates across six species, leaving aged humans with uniquely high mutational burdens and…Cortical neurons gain mutations at similar yearly rates across six species, leaving aged humans with uniquely high mutational burdens and transcriptomic dysregulation. In a preprint analyzing humans, chimpanzees, rhesus macaques, marmosets, ferrets, and mice, researchers evaluated genomic…
Reversible oxidation of a single cysteine residue enables core autophagosome formation and prevents severe tissue pathology during nutrient limitation…Reversible oxidation of a single cysteine residue enables core autophagosome formation and prevents severe tissue pathology during nutrient limitation in mice. In human cells and mice, researchers investigated how dietary restriction directs cellular adaptation through reactive oxygen…
Fibroblasts from individuals at risk for rheumatoid arthritis exhibit impaired adipogenic differentiation and downregulated DNA repair and cell cycle…Fibroblasts from individuals at risk for rheumatoid arthritis exhibit impaired adipogenic differentiation and downregulated DNA repair and cell cycle pathways. In a human cell study, researchers analyzed primary lymph node fibroblasts from healthy controls, individuals at risk of…
Researchers identified coordinated changes in DNA methylation, miRNAs, and gene expression distinguishing older female monkeys with slower gait from…Researchers identified coordinated changes in DNA methylation, miRNAs, and gene expression distinguishing older female monkeys with slower gait from middle-aged counterparts. In a preprint, researchers analyzed vastus lateralis leg muscle from female vervet monkeys (Chlorocebus aethiops…
Aged Cladonema medusae show stem cell depletion, increased DNA damage, delayed wound closure, and defective blastema formation during tentacle repair.Aged Cladonema medusae show stem cell depletion, increased DNA damage, delayed wound closure, and defective blastema formation during tentacle repair. In the cnidarian Cladonema pacificum, aging impairs tissue maintenance and blastema-mediated tentacle regeneration during the medusa stage.
Erastin and RSL3 shortened survival dose-dependently, an effect rescued by ferrostatin-1, while altering iron and lipid profiles selectively in males.Erastin and RSL3 shortened survival dose-dependently, an effect rescued by ferrostatin-1, while altering iron and lipid profiles selectively in males. Researchers investigated whether the fruitfly Drosophila melanogaster could serve as an in vivo model for ferroptosis by testing the…
Ex vivo tests in young and old mice showed that intact perivascular fat increased aortic stiffness only in older animals, alongside higher fat…Ex vivo tests in young and old mice showed that intact perivascular fat increased aortic stiffness only in older animals, alongside higher fat collagen levels. In mice, the adipose tissue surrounding the aorta alters vessel mechanics during aging.
Researchers found that senescent epithelial cells secrete TGF-beta1 to reprogram fibroblasts into a matrix-remodeling state, which senolytic treatment…Researchers found that senescent epithelial cells secrete TGF-beta1 to reprogram fibroblasts into a matrix-remodeling state, which senolytic treatment can blunt. Using human prostate cancer specimens, single-cell datasets, Pten-deficient mice, and mouse cell cultures, researchers evaluated…
A multi-omic analysis shows that defective luteal resolution and CHK2-driven inflammation drive ovarian aging, but drug inhibition restores oocyte…A multi-omic analysis shows that defective luteal resolution and CHK2-driven inflammation drive ovarian aging, but drug inhibition restores oocyte maturation. In a new preprint, researchers analyzed ovaries from young and reproductively aged mice after synchronized ovulation.
The three-dimensional cell platform maintains biological aging markers while spontaneously developing hallmark pathologies of sporadic Alzheimer…The three-dimensional cell platform maintains biological aging markers while spontaneously developing hallmark pathologies of sporadic Alzheimer disease. In a new preprint, researchers developed directly induced neuronal spheroids using primary fibroblasts from young, unimpaired aged, and…
An analysis of 730,088 participants across four cohorts found clonal hematopoiesis was strongly associated with incident frailty and faster functional…An analysis of 730,088 participants across four cohorts found clonal hematopoiesis was strongly associated with incident frailty and faster functional decline. In an observational preprint examining 730,088 human participants from the UK Biobank, All of Us, BioVU, and the Women's Health…
