A5013113087- Genetics, Aging, and Longevity in Model Organisms
- Fungal and yeast genetics research
- Nuclear Structure and Function
- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Sirtuins and Resveratrol in Medicine
- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- Dietary Effects on Health
- Genomics and Chromatin Dynamics
- Circadian rhythm and melatonin
- Genetic factors in colorectal cancer
- CRISPR and Genetic Engineering
- Diet and metabolism studies
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Frailty in Older Adults
- Endoplasmic Reticulum Stress and Disease
- Muscle Physiology and Disorders
- Genetic Neurodegenerative Diseases
- Birth, Development, and Health
- RNA and protein synthesis mechanisms
- Aging and Gerontology Research
- RNA modifications and cancer
National University of Singapore
2017-2025
National University Health System
2018-2025
Buck Institute for Research on Aging
2014-2024
BMJ Group (United Kingdom)
2024
Transnational Press London
2024
University of Southern California
2024
Singapore Institute for Clinical Sciences
2018-2023
Agency for Science, Technology and Research
2019-2023
Yale-NUS College
2023
University of Idaho
2023
Calorie restriction increases life span in many organisms, including the budding yeast Saccharomyces cerevisiae . From a large-scale analysis of 564 single-gene–deletion strains yeast, we identified 10 gene deletions that increase replicative span. Six these correspond to genes encoding components nutrient-responsive TOR and Sch9 pathways. tor1 D or sch9 cells failed further and, like calorie restriction, deletion either SCH9 TOR1 increased independent Sir2 histone deacetylase. We propose...
Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a proinflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating nonspecifically, often with adverse reactions. In accord prior work, we show that several chemotherapeutic drugs induce of primary murine and human cells. Using transgenic mouse permits tracking eliminating senescent cells, therapy-induced (TIS) persist contribute to local...
Chronological life span (CLS) in Saccharomyces cerevisiae , defined as the time cells a stationary phase culture remain viable, has been proposed model for aging of post-mitotic tissues mammals. We developed high-throughput assay to determine CLS ∼4800 single-gene deletion strains yeast, and identified long-lived carrying mutations conserved TOR pathway. signaling regulates multiple cellular processes response nutrients, especially amino acids, raising possibility that decreased mediates...
Resveratrol, a small molecule found in red wine, is reported to slow aging simple eukaryotes and has been suggested as potential calorie restriction mimetic. Resveratrol also act sirtuin activator, this property proposed account for its anti-aging effects. We show here that resveratrol substrate-specific activator of yeast Sir2 human SirT1. In particular, we observed that, vitro, enhances binding deacetylation peptide substrates contain Fluor de Lys, non-physiological fluorescent moiety, but...
In eukaryotic cells, histone gene expression is one of the major events that mark entry into S phase. While this process tightly linked to cell cycle position, how it regulated by machinery not known. Here we show NPAT, a substrate cyclin E–Cdk2 complex, associated with human replication-dependent clusters on both chromosomes 1 and 6 in We demonstrate NPAT activates transcription activation dependent promoter elements (SSCSs) previously proposed mediate cycle–dependent transcription. Cyclin...
Calorie restriction slows aging and increases life span in many organisms. In yeast, a mechanistic explanation has been proposed whereby calorie by activating Sir2. Here we report the identification of Sir2-independent pathway responsible for majority longevity benefit associated with restriction. Deletion FOB1 overexpression SIR2 have previously found to increase reducing levels toxic rDNA circles aged mother cells. We find that combining either these genetic interventions dramatically...
The molecular mechanisms that cause organismal aging are a topic of intense scrutiny and debate. Dietary restriction extends the life span many organisms, including yeast, efforts underway to understand biochemical genetic pathways regulate this extension in model organisms. Here we describe mechanism by which dietary yeast chronological span, defined as length time stationary cells remain viable quiescent state. We find under standard culture conditions is result cell-extrinsic component...
Rapamycin treatment of a mouse model for human laminopathy improves cardiac and muscle function, suggesting therapy patients.
Summary A partial reduction in food intake has been found to increase lifespan many different organisms. We report here a new dietary restriction regimen the nematode Caenorhabditis elegans , based on standard agar plate assay, which adult worms are maintained absence of bacterial source. These findings represent first any organism extension response prolonged starvation. Removal increases greater extent than through mechanism that is distinct from insulin/IGF‐like signaling and Sir2‐family...