Aging & Longevity

Ding et al. mapped over 7,000 plasma proteins to more than 40 cell types and developed machine learning aging clocks across 60,000 individuals, demonstrating that cell-type-specific biological aging is heterogeneous, measurable from blood alone, and powerfully predictive of neurodegenerative disease, cancer, and mortality up to 15 years before clinical onset.¹.

High-throughput single-cell omics of non-human primate brain tissue provides a powerful platform to investigate the molecular basis of brain aging. Here, we present a comprehensive transcriptomic and chromatin accessibility atlas of 2,955,873 nuclei from eight brain regions of 23 female cynomolgus macaques spanning the adult lifespan, including exceptionally old individuals. Our analyses reveal dynamic, cell-subtype- and region-specific age-related changes in core brain functions, including...

In a Nature Medicine study, Tian et al. identify larger biological age gaps associated with early-onset lung, colorectal, and uterine cancers across birth cohorts. These findings position biological age as an integrative marker of physiological dysregulation. Future work combining aging clocks and mutational signatures could distinguish tumor-promoting states from tumor-initiating exposures.

Advanced age is accompanied by progressive metabolic, nutritional, mitochondrial, and neuroimmune dysregulation, which may increase susceptibility to neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), highlighting the need to identify modifiable mechanisms that influence disease initiation and progression. Increasing evidence indicates that nutrition, sleep, and circadian rhythms function as an interconnected biological network regulating metabolic...

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Behaviour change techniques (BCTs) are recommended as core components of physical activity (PA) interventions for people with lower limb osteoarthritis (OA), and identifying effective BCTs is an emerging research priority. This systematic review aimed to evaluate the effects of combined behaviour change and exercise interventions on objectively measured total PA (primary outcome) and other device-measured activity behaviours, including moderate-to-vigorous physical activity (MVPA), steps and...

Vascular aging, not only a victim of vascular cell senescence but also a driving hub of systemic aging, is a complex process in which both anti-aging and pro-aging proteins are involved. Thus, the ideal anti-aging medication should have multiple protein targets; in this case, an lncRNA might be a good choice. AK050834 is a conserved lncRNA, but its roles in vascular biology and vascular aging are currently unknown. Here, we identified that AK050834 was highly expressed in vascular walls and in...

Root-associated beneficial microbes prime host plants for induced systemic resistance (ISR) in leaves. Although continuous immune activation triggered by root endophytic fungi would impair leaf growth, how host plants avoid autoimmunity during endophytic fungi-mediated ISR priming is unknown. Here, we show that the Arabidopsis NatA N-terminal-acetyltransferase complex acts as a leaf-intrinsic brake on these root-to-leaf systemic responses. Impairment of the NatA subunit SUF1 (also named HYPK) or...

Aging-associated loss of chromatin compaction is linked to derepression of retrotransposable elements (RTEs) in mouse and human tissues. Whether such RTE transcription contributes to the microglia activation that is common in aged brains is unknown. Here, we show that DAXX, a histone chaperone and RTE repressor, is downregulated during aging, preserves microglia homeostasis and inhibits cellular senescence. Loss of Daxx in young-adult microglia drives a reactive phenotype marked by chromatin...

Metabolic aging underlies a cluster of chronic conditions-type 2 diabetes, cardiovascular disease, sarcopenia, and neurodegeneration-that account for a substantial share of global morbidity and mortality. A common feature is progressive mitochondrial dysfunction: impaired bioenergetics, disrupted quality control, and loss of metabolic resilience. Reduced mitochondrial DNA copy number in peripheral blood leukocytes is associated with cardiometabolic disease and mortality, but pre-analytical...

Macroautophagy/autophagy is a critical cellular degradation pathway essential for neuronal proteostasis and synaptic function. Its decline with aging is associated with synaptic dysfunction and reduced circuit resilience. NPY (neuropeptide Y), a highly abundant brain neuropeptide, has emerged as an important regulator of autophagy and aging-related processes. In Drosophila, the NPY-family peptide sNPF modulates age-related changes in presynaptic architecture via non-cell autonomous mechanisms....

Neuromodulation techniques in the gamma frequency range, such as chronic 40 Hz sensory stimulation, have gained attention for their potential to impact and preserve cognitive function in the context of neurodegenerative disorders such as Alzheimer's disease (AD). This hypothesis and theory article aims to examine the overlap in biological phenotypes between gamma stimulation techniques and to propose a theoretical mechanism of action that may help to inform future empirical investigations. In...

Age is the primary risk factor for neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, which are characterized by profound loss of midbrain dopaminergic neurons and basal forebrain cholinergic neurons, respectively. In addition, loss of these neurons can occur even in "normal" (i.e., non-pathological) aging, and as a result there is growing recognition of the value of aged animals in studying both normal aging and age-related neurodegenerative disease. The Fischer...

CONCLUSION: Physical performance impairment is strongly associated with balance disorders among older adults, and this relationship is influenced by sociodemographic factors. These findings suggest that sociodemographic characteristics should be considered when evaluating the relationship between physical performance and balance disorders in older adults.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease lacking clarity on the mechanisms linking epithelial injury to fibrotic remodeling. Here, we identify the microbiota-derived corisin as a potent, multifaceted driver of epithelial injury and pulmonary fibrosis. Leveraging targeted DNA sequencing of bronchoalveolar lavage fluid, we provide the first sequence-based identification of corisin in IPF patients and show that functional depletion of native corisin from patient...

Protein restriction extends lifespan across species and engages many hallmarks of aging. We propose that these diverse responses can be understood as components of a single coordinated physiological state. This response involves both cellular nutrient sensing and endocrine and neural coordination, with enhanced longevity emerging from this adaptive response.

Ovarian aging may contribute to systemic aging via the ovarian-systemic axis. This review outlines intrinsic ovarian cellular defects such as genomic instability, epigenetic shifts, and mitochondrial and proteostasis damage, which may trigger senescence-associated secretory phenotype (SASP)-related inflammaging, fibrosis, and distal pro-aging signals. Ovarian-derived endocrine disruption, especially estrogen decline, broadly affects bodily physiology. We summarize emerging multimodal...

Cellular senescence and immune dysfunction intersect as central biological processes shaping disease progression and therapeutic responses across ageing-related pathologies. Rather than acting independently, senescent cells (SnCs) and immune cells engage in a dynamic and bidirectional crosstalk that influences immune surveillance, inflammatory signaling, and tissue remodeling. This review focuses on the molecular and cellular mechanisms through which SnCs modulate immune composition and...

Ageing destabilizes metabolic and neuronal regulatory networks, increasing vulnerability to type 2 diabetes (T2D) and neurodegenerative disorders. These conditions are not independent disease entities but interconnected manifestations of accelerated neuro-metabolic ageing, driven by convergent impairments in insulin signaling, nutrient sensing, mitochondrial bioenergetics, redox homeostasis, proteostasis, and chronic inflammation - processes mediated through conserved hubs including AMPK, mTOR,...

Aging remodels compartmentalized nicotinamide adenine dinucleotide (NAD⁺) circuits in ways that influence stress responses, senescence, tissue repair and susceptibility to fibrosis. Beyond its classical role as a redox cofactor, NAD⁺ fuels sirtuins, PARPs and CD38, linking cellular metabolism to chromatin remodeling, DNA repair, calcium signaling and cell fate. A central translational question is whether modulating NAD⁺ in a given tissue and time window will favor regeneration, restrain fibrotic...