Monica Driscoll

Rutgers, The State University of New Jersey | Rutgers · Department of Molecular Biology and Biochemistry

Ever since the discovery more than 30 years ago of mutations capable dramatically increasing lifespan, there has been an increasing push to find genetic pathways and chemical interventions that ameliorate the effects of aging and increase healthspan and longevity. But aging is not merely “getting old,” it is an accelerating rate of the decline in f...

Aging is a pan-metazoan process with significant consequences for human health and society—discovery of new compounds that ameliorate the negative health impacts of aging promise to be of tremendous benefit across a number of age-based co-morbidities. One method to prioritize a testable subset of the nearly infinite universe of potential compounds...

Aging is a pan-metazoan process with significant consequences for human health and society—discovery of new compounds that ameliorate the negative health impacts of aging promise to be of tremendous benefit across a number of age-based co-morbidities. One method to prioritize a testable subset of the nearly infinite universe of potential compounds...

The choice of statistical test is a fundamentally important one when analyzing experimental data. Here, we consider the question of categorical data, defined by their properties (for example color) rather than by continuous numbering. Using simple and complex example datasets generated from Caenorhabditis elegans research, we conduct a statistical...

Aging is a pan-metazoan process with significant consequences for human health and society—discovery of new compounds that ameliorate the negative health impacts of aging promise to be of tremendous benefit across a number of age-based co-morbidities. One method to prioritize a testable subset of the nearly infinite universe of potential compounds...

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate the extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here, we documen...

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here we document tha...

Aging is characterized by declining health that results in decreased cellular resilience and neuromuscular function. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of pharmacological anti-aging interventions. Here we assessed swimming performa...

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here we document tha...

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here we document tha...

While autophagy genes are required for lifespan of long-lived animals, their tissue-specific roles in aging remain unclear. Here, we inhibited autophagy genes in Caenorhabditis elegans neurons, and found that knockdown of early-acting autophagy genes, except atg-16.2, increased lifespan, and decreased neuronal PolyQ aggregates, independently of aut...

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here we document tha...

The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetica...

Toxic protein aggregates can spread among neurons to promote human neurodegenerative disease pathology. We found that in C. elegans touch neurons intermediate filament proteins IFD-1 and IFD-2 associate with aggresome-like organelles and are required cell-autonomously for efficient production of neuronal exophers, giant vesicles that can carry aggr...

C. elegans neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that...

The Caenorhabditis Intervention Testing Program (CITP) seeks to identify robust and reproducible pro-longevity interventions affecting a genetically diverse panel of representative Caenorhabditis strains from each of 3 species – C. elegans, C. briggsae, and C. tropicalis. The CITP test strains represent genetic diversity on the order of mouse to hu...

Many efficacious interventions that promote mouse longevity (sirtuins, TOR, insulin signaling) have identification roots in invertebrate genetics. The Caenorhabditis Intervention Testing Program (CITP) was charged by the NIA to evaluate pharmacological interventions that promote healthy aging in a robust and reproducible manner across diverse genet...

While autophagy is key to maintain cellular homeostasis, tissue-specific roles of individual autophagy genes are less understood. To study neuronal autophagy in vivo, we inhibited autophagy genes specifically in C. elegans neurons, and unexpectedly found that knockdown of early-acting autophagy genes, i.e., involved in formation of the autophagosom...

Eliminating mitochondrial superoxide dismutase (SOD) causes neonatal lethality in mice and death of flies within 24 hours after eclosion. Deletion of mitochondrial sod genes in C. elegans impairs fertility as well, but surprisingly is not detrimental to survival of progeny generated. The comparison of metabolic pathways among mouse, flies and nemat...

In human neurodegenerative diseases, toxic protein aggregates can spread between neurons to promote pathology. In the transparent genetic animal model C. elegans , stressed neurons can concentrate fluorescently tagged protein aggregates and organelles and extrude them in large, nearly soma-sized, membrane-bound vesicles called exophers that enter n...

C. elegans neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that...

When animals are faced with food depletion, food search-associated locomotion is crucial for their survival. Although food search-associated locomotion is known to be regulated by dopamine, it has yet to investigate the potential molecular mechanisms governing the regulation of genes involved in dopamine metabolism (e.g., cat-1, cat-2) and related...

The Caenorhabditis Intervention Testing Program (CITP) was founded on the principle that compounds with positive effects across a genetically diverse test-set should have an increased probability of engaging conserved biochemical pathways with mammalian translational potential. To fulfill its mandate, the CITP uses a genetic diversity panel of Caen...

Aging is characterized by declining health that results in decreased neuromuscular function and cellular resilience. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of anti-aging interventions. Here we combined survival under thermal and oxidat...

Metformin, the most commonly prescribed anti-diabetes medication, has multiple reported health benefits, including lowering the risks of cardiovascular disease and cancer, improving cognitive function with age, extending survival in diabetic patients, and, in several animal models, promoting youthful physiology and lifespan. Due to its longevity an...

The Caenorhabditis Intervention Testing Program (CITP) is an NIH–funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetica...

Significance In neurodegenerative disease, protein aggregates spread to neighboring cells to promote pathology. The in vivo regulation of toxic material transfer remains poorly understood, although mechanistic understanding should reveal previously unrecognized therapeutic targets. Proteostressed Caenorhabditis elegans neurons can concentrate prote...

Extended space travel is a goal of government space agencies and private companies. However, spaceflight poses risks to human health and the effects on the nervous system have to be better characterized. Here, we exploited the unique experimental advantages of the nematode Caenorhabditis elegans to explore how spaceflight affects adult neurons in v...

Extended space travel, such as crewed missions to Mars and beyond, is a goal for both government space agencies and private companies. Research over the past decades, however, has shown that spaceflight poses risks to human health, including negative effects on musculoskeletal, cardiovascular, and immune systems. Details regarding effects on the ne...

Caenorhabditis elegans (C. elegans) lifespan assays constitute a broadly used approach for investigating the fundamental biology of longevity. Traditional C. elegans lifespan assays require labor-intensive microscopic monitoring of individual animals to evaluate life/death over a period of weeks, making large-scale high throughput studies impractic...

In this study, we report a microfuidic device for the whole-life culture of the nematode Caenorhabditis elegans that allows the scoring of animal survival and health measures. This device referred to as the NemaLife chip features: (1) an optimized micropillar arena in which animals can crawl, (2) sieve channels that separate progeny and prevent the...

High glucose diets are unhealthy, although the mechanisms by which elevated glucose is harmful to whole animal physiology are not well understood. In Caenorhabditis elegans, high glucose shortens lifespan, while chemically inflicted glucose restriction promotes longevity. We investigated the impact of glucose metabolism on aging quality (maintained...

Determining the physical performance of humans using several measures is essential to evaluating the severity of diseases, understanding the role of environmental factors, and development of therapeutic interventions. Development of analogous measures of physical performance in model organisms can help in identifying conserved signaling pathways an...

Oenothein B (OEB) has extensive biological activities, but few investigations have been reported about the pharmacologic influence of OEB on longevity in any organism. To explore potential pharmacological ability of OEB to postpone the progression of age-related degenerative processes and diseases, we monitored the effects of OEB isolated from Euca...

The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully...

A positive correlation exists between stress resistance and longevity, but emerging evidence suggests that lifespan and stress endurance are physiologically distinct. A major challenge in aging biology has been identifying factors that play distinct roles in these closely coupled processes because genes that promote longevity often enhance stress r...

Whole-organism phenotypic assays are central to the assessment of neuromuscular function and health in model organisms such as the nematode C. elegans. In this study, we report a new assay format for engaging C. elegans in burrowing that enables rapid assessment of nematode neuromuscular health. In contrast to agar environments that pose specific d...

A major challenge in regenerative medicine is the repair of injured neurons. Regeneration of laser-cut C. elegans neurons requires early action of core apoptosis activator CED-4/Apaf1 and CED-3/caspase. While testing models for CED-4 as a candidate calcium-sensitive activator of repair, we unexpectedly discovered that amino acid substitutions affec...

The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully...

Stress resistance and longevity are positively correlated but emerging evidence indicates that they are physiologically distinct. Identifying factors with distinctive roles in these processes is challenging because pro-longevity genes often enhance stress resistance. We demonstrate that TCER-1, the Caenorhabditis elegans homolog of human transcript...

Caenorhabditis elegans is a powerful animal model in aging research. Standard longevity assays on agar plates involve the tedious task of picking and transferring animals to prevent younger progeny from contaminating age-synchronized adult populations. Large-scale studies employ progeny-blocking drugs or sterile mutants to avoid progeny contaminati...

Whole-organism phenotypic assays are central to the assessment of neuromuscular function and health in model organisms such as the nematode C. elegans . In this study, we report a new assay format for engaging C. elegans in burrowing that enables rapid assessment of nematode neuromuscular health. In contrast to agar environments that pose specific...

Exercise can protect against cardiovascular disease, neurodegenerative disease, diabetes, cancer, and age-associated declines in muscle, immune, and cognitive function. In fact, regular physical exercise is the most powerful intervention known to enhance robustness of health and aging. Still, the molecular and cellular mechanisms that mediate syste...

Caenorhabditis elegans neurons have recently been found to throw out cellular debris for remote degradation and/or storage, adding an "extracellular garbage elimination" option to known intracellular protein and organelle degradation pathways. This Q&A describes initial insights into the biology of seemingly selective protein and organelle eliminat...

Identifying compounds that increase longevity is made difficult by complexities engendered by heterogeneity in mortality and the noisiness of lifespan itself as an object of study. It is perhaps then not surprising that reproducibility has been a major issue within the field. The Caenorhabditis Intervention Testing Program (CITP) addresses both rep...

Muscle strength is a functional measure of quality of life in humans. Declines in muscle strength are manifested in diseases as well as during inactivity, aging, and space travel. With conserved muscle biology, the simple genetic model C. elegans is a high throughput platform in which to identify molecular mechanisms causing muscle strength loss an...

Exercise and caloric restriction improve health, including reducing risk of cardiovascular disease, neurological disease, and cancer. However, molecular mechanisms underlying these protections are poorly understood, partly due to the cost and time investment of mammalian long-term diet and exercise intervention studies. We subjected Caenorhabditis...

Many aspects of the biology of the ageing process have been elucidated using C. elegans as a model system. As they grow older, nematodes undergo significant physical and behavioural declines that are strikingly similar to what is seen in ageing humans. Most of the major tissue systems of C. elegans, including the cuticle (skin), hypodermis, muscles...

Quinoa (Chenopodium quinoa Willd.) phytochemicals have exhibited metabolic benefit in mammals, though their effects on aging and mechanisms of action remain unknown. Caenorhabditis elegans offers a practical in vivo model to study bioactivity since major metabolic pathways are conserved across phyla. We explored the effects of phytoecdysteroid-enri...

Cellular metabolism is regulated by the mTOR kinase, a key component of the molecular nutrient sensor pathway that plays a central role in cellular survival and aging. The mTOR pathway promotes protein and lipid synthesis and inhibits autophagy, a process known for its contribution to longevity in several model organisms. The nutrient-sensing pathw...

Replicating our work took four years and 100,000 worms but brought surprising discoveries, explain Gordon J. Lithgow, Monica Driscoll and Patrick Phillips.

Levya-Díaz et al. identify a Caenorhabditis elegans gene involved in transgene silencing and RNA interference. Repetitive DNA sequences are subject to gene silencing in various animal species. Under specific circumstances repetitive DNA sequences can escape such silencing. For example, exogenously added, extrachromosomal DNA sequences that are stab...

The Caenorhabditis Intervention Testing Program is a multi-institutional effort to screen promising chemicals for pro-longevity effects across diverse genetic backgrounds. Chemicals that act robustly, across diverse genetic backgrounds, are likely to target conserved pathways and will be promising leads to test in higher organisms, including verteb...

Repetitive DNA sequences are subject to gene silencing in various animal species. Under specific circumstances repetitive DNA sequences can escape such silencing. For example, when exogenously added, extrachromosomal DNA sequences that are stably inherited in multicopy repetitive arrays in the nematode C. elegans are frequently silenced in the germ...

Background: Exercise exerts remarkably powerful effects on metabolism and health, with anti-disease and anti-aging outcomes. Pharmacological manipulation of exercise benefit circuits might improve the health of the sedentary and the aging populations. Still, how exercised muscle signals to induce system-wide health improvement remains poorly unders...