Mouse

Mutation of the mouse klotho gene leads to a syndrome resembling ageing.

A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes. A defect in klotho gene expression in the mouse results in a syndrome that resembles human ageing, including a short lifespan,...

The amyloid hypothesis of Alzheimer's disease at 25 years

Despite continuing debate about the amyloid β-protein (or Aβ hypothesis, new lines of evidence from laboratories and clinics worldwide support the concept that an imbalance between production and clearance of Aβ42 and related Aβ peptides is...

Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas

The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs

The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here,...

PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase

Abstract mTORC1 is an important regulator of muscle mass but how it is modulated by oxygen and nutrients is not completely understood. We show that loss of the prolyl hydroxylase domain isoform 1 oxygen sensor in mice (PHD1 KO ) reduces mus...

TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use

Somatic mutations in the TP53 gene are one of the most frequent alterations in human cancers, and germline mutations are the underlying cause of Li-Fraumeni syndrome, which predisposes to a wide spectrum of early-onset cancers. Most mutatio...

The aging process.

Aging is the progressive accumulation of changes with time that are associated with or responsible for the ever-increasing susceptibility to disease and death which accompanies advancing age. These time-related changes are attributed to the...

Senescent fibroblasts promote epithelial cell growth and tumorigenesis: A link between cancer and aging

Mammalian cells can respond to damage or stress by entering a state of arrested growth and altered function termed cellular senescence. Several lines of evidence suggest that the senescence response suppresses tumorigenesis. Cellular senesc...

Chk1 is an essential kinase that is regulated by Atr and required for the G₂/M DNA damage checkpoint

Chk1, an evolutionarily conserved protein kinase, has been implicated in cell cycle checkpoint control in lower eukaryotes. By gene disruption, we show that CHK1 deficiency results in a severe proliferation defect and death in embryonic ste...

Genetics and biology of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a median survival of <6 mo and a dismal 5-yr survival rate of 3%-5%. The cancer's lethal nature stems from its propensity to rapid...

Cellular senescence mediates fibrotic pulmonary disease

Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by interstitial remodelling, leading to compromised lung function. Cellular senescence markers are detectable within IPF lung tissue and senescent cell deletion rejuvenate...

Metformin improves healthspan and lifespan in mice