Aging & Longevity

CONCLUSIONS: These findings emphasize the importance of sex-specific nutritional interventions and stable food supply systems for preventing frailty in aging populations.

Metformin use may be associated with reduced risk of all-cause mortality as well as prevent the onset of diseases of aging, namely cardiovascular diseases (CVD), cancer, and dementia. We systematically reviewed recent studies to determine whether metformin can promote healthspan in people with type 2 diabetes mellitus (T2DM). A comprehensive literature search was conducted using Medline, Embase, and Scopus for randomized controlled trials (RCTs) and cohort studies evaluating the effect of...

Aging-related declines in spatial navigation pose significant challenges for older adults' independence and quality of life. Among navigational deficits, older adults have been shown to demonstrate deficits in utilizing allocentric (i.e., world-centered) information and rely on egocentric (i.e., body-centered) cues during navigation, resulting in reference frame bias. We investigated naturalistic navigation performance and allocentric knowledge formation in younger adults (N = 30) and older...

INTRODUCTION: Healthy aging is often accompanied by a loss of hearing sensitivity and a reduced ability to understand speech in both quiet and noisy environments. From a physiological perspective, neural oscillations are thought to fundamentally contribute to parse the speech signal into meaningful units and to extract linguistically relevant information at multiple hierarchical levels. Given that syllables are essential structural elements of the speech signal that recur with quasi-rhythmic...

CONCLUSION: These findings indicate that amyloidosis is associated with reduced reliability of spatial memory performance and impaired handling of competing spatial information, particularly under conditions requiring flexible updating of overlapping mnemonic representations. The results further suggest increased vulnerability to interference-related spatial memory deficits with age. Together, these findings support the utility of the OUL paradigm for studying memory updating impairments in...

Substantial heterogeneity in cognitive ageing is well documented. Such heterogeneity has been attributed to individual differences in brain maintenance - i.e., the relative preservation of neural resources in ageing. However, large-scale longitudinal evidence is currently lacking. In this study, we pooled data from three longitudinal population-based Swedish cohorts (total N = 1 356, 60-93 years at baseline, maximum follow-up duration: 7 years) to assess whether global brain maintenance is...

Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare premature aging disorder caused predominantly by a de novo LMNA c.1824C>T mutation that produces progerin, a truncated and permanently farnesylated lamin A isoform. Progerin accumulation disrupts nuclear lamina integrity and chromatin organization, inducing persistent DNA damage responses, telomere attrition, mitochondrial dysfunction, and cellular senescence. These processes drive a multisystem clinical phenotype characterized by...

Therapy-induced senescence (TIS) in cancer cells can be triggered by radiotherapy, chemotherapy, and certain targeted therapeutics. Here, we demonstrate that a new form of TIS, termed fatty acid synthesis therapy-induced senescence (FASTIS), can be induced by pharmacologically targeting de novo lipogenesis. Cancer cells can evade the anti-proliferative effects of clinically relevant inhibitors of core lipogenic enzymes, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN), by...

G-quadruplexes (G4s) are four-stranded nucleic acid structures that regulate virtually all nucleic acid-dependent cellular processes. At present, most functional studies involving G4s have focused on cancer cells. This study investigated how neurons respond to genotoxic stress induced by quarfloxin (CX-3543), a small molecule that stabilizes G4s. We found that quarfloxin treatment induced DNA damage in neurons, with double-strand breaks enriched in the nucleolus. Proteomic analysis revealed that...

Although senolytics such as dasatinib and quercetin (D+Q) show promise in modulating aging, their tissue-specific efficacy and optimal intervention timing remain poorly understood. Given D+Q's potential off-target effects, incomplete senescent cell clearance and associated hematologic side effects, we performed an unbiased multitissue single-cell analysis in aged mice across different aging phenotypes and tissue contexts. Here through integrative transcriptomics, single-cell technologies,...

Throughout the female reproductive lifespan, the ovary undergoes hundreds of cycles of follicle development, ovulation and tissue regeneration. How aging disrupts the coordination of such precise, multicellular interactions across time and space is not well understood. Using Slide-seq, a near-cellular spatial transcriptomics method, here we profile 22 mouse ovaries across the reproductive cycle and chronological ages, capturing 610,620 spots across 69 spatial profiles. We develop a novel...

Formation in lithium-ion battery manufacturing typically involves low-rate charge-discharge cycles to establish stable electrode-electrolyte interfaces-a time-consuming process^(1-4). Here, our findings on lithium-rich layered oxide cathodes challenge the necessity of conventional formation, which can even shorten battery lifespan. Fast formation, on the other hand, reduces production cost and enhances capacity and stability. Multiscale synchrotron-based techniques show that residual lithium...

The etiology of Alzheimer's disease (AD) remains unclear but is likely driven by gene-environment interactions. We present a multi-organ untargeted metabolomics atlas (n = 2,271) paired with metagenomics data (n = 666) from two AD transgenic mouse models (3xTg and 5xFAD) under colonized and germ-free conditions. Systems-level analyses revealed clusters of dysregulated molecules across tissues, including carnitines, bile acids, B vitamins, neurotransmitters, and N-acyl lipids. Metabolic shifts...

The human heart undergoes continuous transcriptional remodeling from development through aging, yet the cellular and regulatory features governing this process remain incompletely defined. Here, we generated a single-nucleus RNA sequencing atlas of 442,239 nuclei from 54 nonfailing myocardial tissues of 29 individuals spanning development, adulthood, and aging, covering left and right ventricles. Across all major cell types, we uncovered coordinated yet cell type-specific transcriptional...

Cerebrospinal fluid circulation through the glymphatic system plays a crucial role in removing metabolic waste from the central nervous system. However, the mechanism underlying the brain-wide glymphatic dynamics is not yet fully understood, in part due to the lack of glymphatic imaging technologies on deep brains. Here, we report a hybrid imaging technology that integrates three-dimensional photoacoustic tomography and ultrasound localization microscopy (3D-PAULM), enhanced by a photoacoustic...

Peripheral tolerance depends on limiting conventional T cell responses to self-antigens. To define the contribution of nutritional factors and related epigenetic regulation, we perform in vivo CRISPR screening and identify the ascorbate transporter Slc23a2 as a key regulator of naive T cell (Tn) reactivity. T cell-specific loss of Slc23a2 reduces intracellular ascorbate, induces regional DNA hypermethylation, enhances differentiation of Tn cells into effector and memory populations, and promotes...

STING is an innate immune adaptor, classically activated by cytosolic DNA via cGAS-cGAMP to induce interferon signaling. Recent studies reveal that STING participates in non-canonical signaling pathways and localizes to the nucleus, where its functions remain poorly understood. In Hutchinson-Gilford Progeria Syndrome (HGPS), a premature aging disease caused by expression of the lamin-A mutant protein 'progerin', STING accumulates in the nucleus and drives chronic inflammation. Here, we show that...

With the global rise in life expectancy, promoting healthy aging has become a central focus in biomedical research. From global initiatives like The World Health Organization's Decade of Healthy Ageing (2021-2030) to local ones, they highlight the need for accessible, non-invasive, and cost-effective tools to monitor aging-related physiological changes. Since the hand skin is an easily accessible tissue, it can offer valuable insights into aging processes, influenced by age, gender, and...

Frailty is a heterogeneous aging phenotype that represents accumulated biological vulnerability among very old adults. How frailty relates to key late-life transitions at advanced ages remains incompletely understood. We examined the longitudinal association between frailty status and a composite endpoint of incident long-term care insurance certification (level ≥ 2) or death, and assessed whether circulating biomarkers (growth differentiation factor-15 [GDF-15] and N-terminal pro-B-type...

CONCLUSIONS: Resistance exercise exerts significant beneficial effects on handgrip strength, ASMI, gait speed, and physical performance, as assessed by the five-times sit-to-stand test, in older adults with sarcopenia.