Whole-genome studies of aging, GWAS, and longevity-associated variants
AIMS: Numerous preclinical studies suggested that targeted inhibition of mammalian target of rapamycin (mTOR) may be beneficial for the treatment of osteoporosis. However, the relevance of these findings to human populations remains unclear. We hypothesized …
The CRISPR/Cas9 method facilitates targeted disruption of gene sequences, providing a reliable means to analyze gene-dependent regulatory pathways. This study aims to investigate melanogenesis in p21-knockout B16F1 cells generated by the CRISPR/Cas9 system. The mutation …
Approximately 10%-15% of human cancers maintain their telomeres through alternative lengthening of telomeres (ALT), a recombination-based pathway that exploits chronic telomeric replication stress to drive telomere elongation. Although initiated in S phase, ALT-associated telomere synthesis …
Lysosomal dysfunction is a prominent feature of neurodegeneration and aging, yet how primary defects in lysosomal trafficking are converted into progressive cellular decline remains poorly understood. Niemann Pick disease type C (NPC), caused by impaired …
Age is the dominant risk factor for cardiovascular disease, yet individuals of the same chronological age can differ markedly in the organs and biological pathways through which cardiovascular vulnerability emerges. We used deep learning to …
The aberrant DNA methylation is a characteristic feature of solid tumours, but the imbalance of DNA methyltransferases and demethylases has not been studied at the network level across breast and lung cancers. To determine the …
The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of …
Intermittent fasting (IF) ameliorates metabolic dysfunction-associated steatotic liver disease (MASLD), but the underlying mechanism remains unclear. Combined CUT&Run and transcriptomic analysis shows that hepatic Ahcy is controlled by the super‑enhancer (SE) and acts as a …
Human longevity is a complex trait shaped by genetic background and population-specific factors. Calabria, a region in Southern Italy with a high prevalence of centenarians and relative genetic isolation, is a valuable model for investigating …
Aging is a dynamic and time-dependent process characterized by progressive functional decline across biological systems. Key hallmarks, including genomic instability, telomere attrition, loss of proteostasis, mitochondrial dysfunction, and immunosenescence, have been widely described, each reflecting …
Aging is characterized by progressive oxidative stress, mitochondrial dysfunction, chronic inflammation and intestinal barrier impairment, contributing to increased susceptibility to age-associated disorders. Targeting redox imbalance and epithelial dysfunction represents a promising therapeutic strategy to promote …
CTC1-STN1-TEN1 (CST) is a heterotrimeric, RPA-like complex that binds single-stranded DNA, stimulates DNA polymerase α-primase, and functions in several genome maintenance pathways, including telomere maintenance and DNA replication and repair. During telomere replication, CST prevents …
Researchers identified six genetic variants linked to living past 85, 90, and 95 years in a Taiwanese population. When combined with health information, these genetic clues modestly improved predictions of extreme longevity, especially for those …
Fasting is an effective physiological intervention eliciting global and cellular adaptations that can improve healthspan and lifespan. In addition to its metabolic effects, fasting is a state of modulation of aging-associated processes/adaptive cellular responses that …
Tumor heterogeneity and cellular plasticity are major drivers of therapeutic failure across many cancer types. While precision oncology has largely focused on static genomic alterations, growing evidence indicates that tumors behave as dynamic biological systems …
Experimental evolution studies with Drosophila melanogaster have long played a role in the effort to dissect the genetic basis of aging and longevity. While selection for postponed reproduction reliably extends lifespan, additional phenotypic consequences and …
Background and Aims: Dilated cardiomyopathy (DCM) is a genetically heterogeneous cause of heart failure and sudden cardiac death. Many patients remain without a molecular diagnosis. MAP3K7 encodes TAK1, a serine/threonine kinase important for cardiac homeostasis. …
The APOE gene is a critical determinant of human healthspan and longevity, with the rare{varepsilon} 2 allele traditionally viewed as a universal protective factor against Alzheimer s disease (AD) and a driver of exceptional lifespan. …
BACKGROUND: Antagonistic pleiotropy between fertility and survival suggests testosterone may promote fertility at the expense of survival. We investigated sex-specific effects of testosterone on fertility (offspring number) and lifespan (proxied by maternal and paternal attained …
Glioblastoma is a highly aggressive primary brain tumour marked by extensive genomic and epigenomic alterations, cellular heterogeneity, and therapeutic resistance. Despite maximal surgical resection followed by chemoradiotherapy, median survival remains approximately 15 months, reflecting the …