Cellular reprogramming can reverse the aging that leads to a decline in the activities and functions of mesenchymal stem/stromal cells (MSCs). This is something that scientists have known for a while. But what they had not figured out is which molecular mechanisms are responsible for this reversal. A study released today in STEM CELLS appears to have solved this mystery. It not only enhances the knowledge of MSC aging and associated diseases, but also provides insight into developing pharmacological strategies to reduce or reverse the aging process.
The research team, made up of scientists at the University of Wisconsin-Madison, relied on cellular reprogramming — a commonly used approach to reverse cell aging — to establish a genetically identical young and old cell model for this study. “While agreeing with previous findings in MSC rejuvenation by cellular reprogramming, our study goes further to provide insight into how reprogrammed MSCs are regulated molecularly to ameliorate the cellular hallmarks of aging,” explained lead investigator, Wan-Ju Li, Ph.D., a faculty member in the Department of Orthopedics and Rehabilitation and the Department of Biomedical Engineering.
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They say age breeds wisdom. But can we grow personally and mature, while staying young and healthy? Can ageing be cured just like any other disease? We asked David Sinclair, professor of genetics at Harvard Medical School.
David Andrew Sinclair is an Australian biologist and Professor of Genetics best known for his research on the biology of lifespan extension and driving research towards treating diseases of aging.
Sinclair is Co-Director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School. Sinclair obtained a Bachelors of Science (Honours Class I) at the University of New South Wales, Sydney, and received the Australian Commonwealth Prize. In 1995, he received a Ph.D. in Molecular Genetics then worked as a postdoctoral researcher at the Massachusetts Institute of Technology with Leonard Guarente. Since 1999 he has been a tenured professor in the Genetics Department of Harvard Medical School.
Sinclair has received over 25 awards including The Australian Commonwealth Prize, A Helen Hay Whitney Fellowship, the Nathan Shock Award, a Leukemia and Lymphoma Fellow, a MERIT Awards from the National Institutes of Health, the Merck Prize, the Arminese Fellowship, the Genzyme Outstanding Achievement in Biomedical Science Award, an Ellison Medical Senior Fellow, the Bio-Innovator award, the Bright Sparks Award for Top Scientists under 40, The Denham Harman Award in Biogerontology, a medal from the Australian Society for Medical Research, and a TIME 100 honoree, TIME magazine’s list of the 100 “most influential people in the world” (2014).
We will be joined by Morgan Levine, Yale University, to discuss the recent article “Underlying Features of Epigenetic Aging Clocks” she co-authored.
The talk will compare and contrast existing epigenetic clocks and describe how they can be deconstructed to facilitate our understanding of causes and consequences of epigenetic aging.
Article Abstract:
Epigenetic clocks, developed using DNA methylation data, have been widely used to quantify biological aging in multiple tissues/cells. However, many existing epigenetic clocks are weakly correlated with each other, suggesting they may capture different biological processes. We utilize multi‐omics data from diverse human tissue/cells to identify shared features across eleven existing epigenetic clocks. Despite the striking lack of overlap in CpGs, multi‐omics analysis suggested five clocks (Horvath1, Horvath2, Levine, Hannum, and Lin) share transcriptional associations conserved across purified CD14+ monocytes and dorsolateral prefrontal cortex. The pathways enriched in the shared transcriptional association suggested links between epigenetic aging and metabolism, immunity, and autophagy. Results from in vitro experiments showed that two clocks (Levine and Lin) were accelerated in accordance with two hallmarks of aging—cellular senescence and mitochondrial dysfunction. Finally, using multi‐tissue data to deconstruct the epigenetic clock signals, we developed a meta‐clock that demonstrated improved prediction for mortality and robustly related to hallmarks of aging in vitro than single clocks.
Morgan’s Bio:
Morgan Levine is a ladder-rank Assistant Professor in the Department of Pathology at the Yale School of Medicine and a member of both the Yale Combined Program in Computational Biology and Bioinformatics, and the Yale Center for Research on Aging. Her work relies on an interdisciplinary approach, integrating theories and methods from statistical genetics, computational biology, and mathematical demography to develop biomarkers of aging for humans and animal models using high-dimensional omics data. As PI or co-Investigator on multiple NIH-, Foundation-, and University-funded projects, she has extensive experience using systems-level and machine learning approaches to track epigenetic, transcriptomic, and proteomic changes with aging and incorporate this information to develop measures of risk stratification for major chronic diseases, such as cancer and Alzheimer’s disease. Her work also involves development of systems-level outcome measures of aging, aimed at facilitating evaluation for geroprotective interventions. A number of the existing biological aging measures she has developed are being applied in both basic and observational research.
AI, Genetics, and Health-Tech / Wearables — 21st Century Technologies For Healthy Companion Animals.
Ira Pastor ideaXme life sciences ambassador interviews Dr. Angela Hughes, the Global Scientific Advocacy Relations Senior Manager and Veterinary Geneticist at Mars Petcare.
The global petcare industry is significantly expanding, with North America sales alone expected to hit US $300 billion by 2025. And while we may associate the Mars Corporation, the world’s largest candy company, with leading confectionary brands like Milky Way, M&M’s, Skittles, Snickers, Twix, etc. They also happen to be one of the world’s largest companies in pet care as well.
Dr. Angela Hughes, is the Global Scientific Advocacy Relations Senior Manager & Veterinary Geneticist at Mars Petcare. Dr. Hughes is both Doctor of Veterinary Medicine, and a PhD with a focus in Canine Genetics, both from the University of California, Davis. Dr. Hughes also serves as Veterinary Genetics Research Manager of Wisdom Health, a business unit of Mars Petcare, which has developed state-of-the-art genetic tests for companion animals, leading to revolutionary personalized petcare. She also serves as a Veterinary Geneticist of Hughes Veterinary Consulting, focused on small animal and equine genetics and with a special interest in small animal reproduction and pediatrics.
Dr Hughes is published in multiple academic journals, including the Journal of the American Veterinary Medical Association and has contributed chapters for publication in Veterinary Clinics of North America Small Animal Practice: Pediatrics and Large Animal Internal Medicine.
On this ideaXme episode we will hear from Dr. Hughes about:
-Her background — how she developed an interest in veterinary medicine and animal genetics, and how she arrived at Mars Petcare.
-Her role as the senior manager of Global Scientific Advocacy Relations at Mars Petcare.
These findings […] strongly suggest that high levels of iron in the blood reduces our healthy years of life, and keeping these levels in check could prevent age-related damage.
Genes linked to ageing that could help explain why some people age at different rates to others have been identified by scientists.
The international study using genetic data from more than a million people suggests that maintaining healthy levels of iron in the blood could be a key to ageing better and living longer.
The findings could accelerate the development of drugs to reduce age-related diseases, extend healthy years of life and increase the chances of living to old age free of disease, the researchers say.
RNA-binding proteins (RBPs) are critical effectors of gene expression, and as such their malfunction underlies the origin of many diseases. RBPs can recognize hundreds of transcripts and form extensive regulatory networks that help to maintain cell homeostasis. System-wide unbiased identification of RBPs has increased the number of recognized RBPs into the four-digit range and revealed new paradigms: from the prevalence of structurally disordered RNA-binding regions with roles in the formation of membraneless organelles to unsuspected and potentially pervasive connections between intermediary metabolism and RNA regulation. Together with an increasingly detailed understanding of molecular mechanisms of RBP function, these insights are facilitating the development of new therapies to treat malignancies. Here, we provide an overview of RBPs involved in human genetic disorders, both Mendelian and somatic, and discuss emerging aspects in the field with emphasis on molecular mechanisms of disease and therapeutic interventions.
Researchers at Lund University in Sweden have discovered a new method to treat human herpes viruses. The new broad-spectrum method targets physical properties in the genome of the virus rather than viral proteins, which have previously been targeted. The treatment consists of new molecules that penetrate the protein shell of the virus and prevent genes from leaving the virus to infect the cell. It does not lead to resistance and acts independently of mutations in the genome of the virus. The results are published in the journal PLOS Pathogens.
Herpes virus infections are lifelong, with latency periods between recurring reactivations, making treatment difficult. The major challenge lies in the fact that all existing antiviral drugs to treat herpes viruses lead to rapid development of resistance in patients with compromised immune systems where the need for herpes treatment is the greatest (e.g. newborn children, patients with HIV, cancer or who have undergone organ transplantation). Both the molecular and physical properties of a virus determine the course of infection. However, the physical properties have so far received little attention, according to researcher Alex Evilevitch.
“We have a new and unique approach to studying viruses based on their specific physical properties. Our discovery marks a breakthrough in the development of antiviral drugs as it does not target specific viral proteins that can rapidly mutate, causing the development of drug resistance — something that remains unresolved by current antiviral drugs against herpes and other viruses. We hope that our research will contribute to the fight against viral infections that have so far been incurable,” says Alex Evilevitch, Associate Professor and senior lecturer at Lund University who, together with his research team, Virus Biophysics, has published the new findings.
Although Drosophila is an insect whose genome has only about 14,000 genes, roughly half the human count, a remarkable number of these have very close counterparts in humans; some even occur in the same order in the fly’s DNA as in our own. This, plus the organism’s more than 100-year history in the lab, makes it one of the most important models for studying basic biology and disease.
To take full advantage of the opportunities offered by Drosophila, researchers need improved tools to manipulate the fly’s genes with precision, allowing them to introduce mutations to break genes, control their activity, label their protein products, or introduce other inherited genetic changes.
“We now have the genome sequences of lots of different animals — worms, flies, fish, mice, chimps, humans,” says Roger Hoskins of Berkeley Lab’s Life Sciences Division. “Now we want improved technologies for introducing precise changes into the genomes of lab animals; we want efficient genome engineering. Methods for doing this are very advanced in bacteria and yeast. Good methods for worms, flies, and mice have also been around for a long time, and improvements have come along fairly regularly. But with whole genome sequences in hand, the goals are becoming more ambitious.”
CRISPR/Cas9 is now a household name associated with genetic engineering studies. Through cutting-edge research described in their paper published in Scientific Reports, a team of researchers from Tokyo University of Science, Meiji University, and Tokyo University of Agriculture and Technology, led by Dr Takayuki Arazoe and Prof Shigeru Kuwata, has recently established a series of novel strategies to increase the efficiency of targeted gene disruption and new gene “introduction” using the CRISPR/Cas9 system in the rice blast fungus Pyricularia (Magnaporthe) oryzae. These strategies include quicker (single-step) gene introduction, use of small homologous sequences, and bypassing of certain prerequisite host DNA “patterns” and host component modification.
The team led by Dr Arazoe and Prof Kuwata has devised simple and quick techniques for gene editing (target gene disruption, sequence substitution, and re-introduction of desired genes) using CRISPR/Cas9 in the rice blast fungus Pyricularia (Magnaporthe) oryzae, a type of filamentous fungus. Spurred on by encouraging results, the researchers surmise, “Plants and their pathogens are still coevolving in nature. Exploiting the mutation mechanisms of model pathogenic fungi as a genome editing technique might lead to the development of further novel techniques in genetic engineering.”
The working component of the CRISPR/Cas9 system binds to the target gene region (DNA) and causes a site-specific double-stranded break (DSB) in the DNA. Effective binding of this component requires a certain “motif” or “pattern” called the protospacer-adjacent motif (PAM), which follows downstream of the target gene region.
For more than two decades, I have been working to improve several staple food crops in Africa, including bananas, plantains, cassavas and yams. As principal scientist and a plant biotechnologist at the International Institute for Tropical Agriculture in Nairobi, I aim to develop varieties that are resistant to pests and diseases such as bacterial wilt, Fusarium wilt (caused by the fungus F. oxysporum) and banana streak virus.
[Editor’s note: Abdullahi Tsanni is a freelance science journalist based in Abuja, Nigeria.]
In 2011, my team and I created a set of tools, the only one of its kind in Africa, for changing DNA sequences so that we could develop genetically modified and genome-edited products in sub-Saharan Africa. In 2018, we pioneered the first application of CRISPR gene-editing technology to deactivate banana streak virus in plantains. This technology overcame a major hurdle in banana breeding on the continent, and is the first reported successful use of genome editing to improve bananas.
