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Abstract
Photobiomodulation (PBM), also known as low-level laser (light) therapy, was discovered
over 50 years ago, but only recently has it been making progress toward wide acceptance.
PBM originally used red and near-infrared (NIR) lasers, but now other wavelengths
and non-coherent light-emitting diodes (LEDs) are being explored. The almost complete
lack of side effects makes the conduction of controlled clinical trials relatively
easy. Laboratory research has mainly concentrated on mammalian cells (normal or cancer)
in culture, and small rodents (mice and rats) as models of different diseases. A sizeable
body of work was carried out in the 1970s and 1980s in Russia looking at various bacterial
and fungal cells. The present review covers some of these studies and a recent number
of papers that have applied PBM to so-called "model organisms." These models include
flies (Drosophila), worms (Caenorhabditis elegans), fish (zebrafish) and caterpillars
(Galleria). Much knowledge about the genomics and proteomics, and many reagents for
these organisms already exist. They are inexpensive to work with and have lower regulatory
barriers compared to vertebrate animals. Other researchers have studied different
models (snails, sea urchins, Paramecium, toads, frogs and chickens). Plants may respond
to NIR light differently from visible light (photosynthesis and photomorphogenesis)
but PBM in plants has not been much studied. Veterinarians routinely use PBM to treat
non-mammalian patients. The conclusion is that red or NIR light does indeed have significant
biologic effects conserved over many different kingdoms, and perhaps it is true that
"all life-forms respond to light."
Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
Soon after the discovery of lasers in the 1960s it was realized that laser therapy had the potential to improve wound healing and reduce pain, inflammation and swelling. In recent years the field sometimes known as photobiomodulation has broadened to include light-emitting diodes and other light sources, and the range of wavelengths used now includes many in the red and near infrared. The term "low level laser therapy" or LLLT has become widely recognized and implies the existence of the biphasic dose response or the Arndt-Schulz curve. This review will cover the mechanisms of action of LLLT at a cellular and at a tissular level and will summarize the various light sources and principles of dosimetry that are employed in clinical practice. The range of diseases, injuries, and conditions that can be benefited by LLLT will be summarized with an emphasis on those that have reported randomized controlled clinical trials. Serious life-threatening diseases such as stroke, heart attack, spinal cord injury, and traumatic brain injury may soon be amenable to LLLT therapy.
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