Aging & Longevity

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.

CONCLUSIONS: Concurrent frailty and depressive symptoms constitute the highest-risk phenotype for cardio-oncology comorbidity in community-dwelling older adults. These findings suggest that combined assessment of frailty and depressive symptoms may improve baseline risk stratification of cardio-oncology comorbidity.

Identification of natural compounds that delay aging and prevent age-related neurodegeneration is a key goal in gerontology. Fucoxanthin, a marine-derived xanthophyll, exhibits potent antioxidant properties, yet its effects on organismal aging and specific molecular mechanisms remain underexplored. Here, we investigated the pro-longevity and neuroprotective effects of fucoxanthin using Caenorhabditis elegans. Fucoxanthin supplementation significantly extended the mean lifespan of wild-type...

Mitochondria are essential for brain energy metabolism and are increasingly recognized as key contributors to brain aging. Although neurons are exceptionally vulnerable to age-related mitochondrial decline, emerging evidence reveals that glial and vascular cells also exhibit distinct mitochondrial impairments. This review synthesizes recent advances in our understanding of mitochondrial dysfunction across specific brain regions and diverse cell types, highlighting subcellular...

Cellular senescence drives aging and disease largely through the senescence-associated secretory phenotype (SASP), yet its regulatory mechanisms remain unclear. Using a SASP reporter combined with a CRISPR-Cas9 screen targeting active regulatory elements, we identify the zinc-finger protein ZNF512B as a key suppressor of the SASP. ZNF512B loss induces DNA damage, activates cGAS-STING signaling, and triggers inflammatory transcriptional reprogramming. In contrast, ZNF512B promotes preferential...

The extracellular matrix (ECM) is a dynamic structural network that supports tissue architecture and regulates cell function. It is primarily composed of collagens, elastin, proteoglycans, and glycoproteins, which are produced by canonical and non-canonical ECM-producing cells. During aging, the ECM undergoes progressive changes in structure and composition, a process recently recognized as the 13th hallmark of aging. In skeletal muscle (SKM), age-associated ECM remodeling, largely regulated by...

Evolution has given rise to lifespans in extant species ranging from days to centuries. Given that mechanisms of ageing are highly conserved, studying long-lived lineages across the animal kingdom could yield insights relevant for healthy ageing in humans. The long lifespans reported for the Heliconius butterfly genus position it as a promising new model system for such studies, but its potential is limited by a paucity of available data. Here, we collate data from commercial butterfly houses,...

The accumulation of mitochondrial DNA (mtDNA) deletion mutants in post-mitotic cells is a hallmark of mammalian ageing and a key contributor to tissue decline in skeletal muscle and neurons. A transcription-coupled replication model predicts that deletions affecting a negative feedback mechanism gain a selective replication advantage, leading to relatively short accumulation times for mutant takeover. However, these accumulation times are experimentally inaccessible since single-cell...