Aging by pollutants: introducing the aging dose (AD)50

Abstract

The global scale of environmental pollution and the accumulation of pollutants in environmental sinks such as soil and surface water sediments call for long-term investigation of relevant target organisms. Consistently, age-resolved toxicology in the nematode roundworm C. elegans revealed that effective concentrations of pollutants such as heavy metals and nanomaterials accelerate a variety of age-related phenotypes from reduced locomotion to amyloid protein aggregation and neurodegeneration. We suggest the definition of this acceleration by introduction of the aging dose (AD) 50 that provides a new metric to characterize adverse effects of pollutants. AD 50 represents any concentration of a pollutant that significantly accelerates an age-related defect in 50% of the exposed individuals. Comparison of pollutant-exposed with unexposed specimen concerning their age when 50% individuals display a specific aging phenotype indicates the time-frame of this acceleration and defines the corresponding reduction of health span. Application of AD 50 is invented in the short-lived nematode C. elegans, however, provides for a research platform to better understand the role of pollutants in aging across different taxa. Toxicology that addresses the entire life span impacts both, environmental protection of wild fauna as well as health protection in the human population. which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

How to keep up with the analysis of classic and emerging neurotoxins: age-resolved fitness tests in the animal model Caenorhabditis elegans – a step-by-step protocol

“…At the late stage of L4, add 36 µl of 6.25 mM of 5-Fluoro-2'-deoxyuridine (FUdR) dissolved in H 2 O to the S-medium in the 96 well microtiter plates, shake the plates at 1000 rpm for 1 min and store them in an incubator at 20 °C 7 . This prevents worms from self-fertilizing and maintains an age-synchronous culture (Gandhi et al,1980[ 10 ]; Petrascheck et al 2007[ 15 ]; Piechulek et al, 2018[ 18 ]).…”

“…Adult C. elegans develop neuromuscular defects in response to pollutants at a certain age and can thereby be identified as vulnerable target age-groups. For example, the age-associated natural decline of locomotion in wild type worms is accelerated by different pollutants (Piechulek and von Mikecz, 2019[ 18 ]). Here, we introduce a life span-resolved fitness test on 96 well and 24 well microtiter plates that enables long-term quantification of the neurobiological response to pollutants.…”

Effects of Airborne Nanoparticles on the Nervous System: Amyloid Protein Aggregation, Neurodegeneration and Neurodegenerative Diseases

“…In single neurons, protein aggregation, neurodegeneration and defective serotonergic as well as dopaminergic neurosignaling has been observed ( Figure 2 ; [ 44 , 45 ]). This is consistent with the idea that silica NPs interfere with key processes of neuronal function, ranging from nerve impulse transduction to neurotransmitter synthesis and mitochondrial energy production.…”

“…Due to the repeated observation that certain nanoparticles reduce the health span of the worms, the concept of an aging dose (AD 50 ) was introduced, which allows for the identification of toxicants that accelerate aging processes in adult C. elegans . The AD 50 enables the detection of nano-sized particles that turn a young worm into an old worm [ 45 ]. While the AD 50 has been established in C. elegans , an organism with a short life span, it may also be useful in long-lived individuals.…”

“…Consistently, widespread protein aggregation likewise included the axons of serotonergic hermaphrodite-specific neuron (HSN; Figure 2 A). In turn, the impaired axonal transport of the neurotransmitter serotonin to the HSN synapse interrupted the neuromuscular circuit of egg laying and promoted the neural defect internal hatch ( Figure 2 B; [ 45 ]). Since protein aggregation in the HSN and internal hatch was rescued by anti-aging compounds that likewise inhibit amyloid formation, it was concluded that silica NPs cause premature aging in C. elegans by a neuropathology driven by imbalanced protein homeostasis.…”