Drug in focus is rapamycin, which functions by inhibiting mTOR pathway. Similar drugs include everolimus. Normally when over-activated by nutrients and insulin, mTOR acts via S6K to inhibit insulin signaling, thereby causing insulin resistance.
The evidence in preclinical and animal suggests that rapamycin is a universal anti-aging drug that is, it extends lifespan in all tested models from yeast to mammals, suppresses cell senescence and delays the onset of age-related diseases, which are manifestations of aging
Author lists advantages of rapamycin which include immunomodulator and anti inflammatory effects in addition to anti aging effects. Also it is know that rapamycin reduces viral replication. Some of the notable side effects include stomatitis and mucositis, non-infectious interstitial pneumonitis and nuetrophil inhibition which can lead to severe bacterial infections.
In addition to rapamycin/everolimus, other conventional drugs with anti-aging effect include metformin, aspirin, ACE inhibitors, angiotensin receptor blockers and PDE5 inhibitors such as Sildenafil and Tadalafil, can prevent or treat more than one age-related disease. In addition to above drugs calorie restriction and intermittent fasting has been shown to extend both the lifespan and healthspan in diverse species.
Dramatic calorie restriction have long been known to boost healthy lifespan and reduce the risk of heart attack, diabetes and other age-related conditions. In animal studies it is shown to extend life span in most animal species examined. Further research has shown that animals fed restricted-calorie diets are also better able to regenerate numerous tissues after injury.
When mice were allowed to eat without limit and were then exposed to radiation, their intestinal cells’ (in red) regeneration was limited (left). Mice fed a calorie-restricted diet showed a greatly enhanced regenerative capacity in their intestinal tissue (right). Credit: University of Pennsylvania.
A new study led by University of Pennsylvania researchers pinpoints the cell responsible for these improved regenerative abilities in the intestines. According to the scientists’ work, when a calorie-restricted mouse is subjected to radiation, a particular type of stem cell in the intestines, known as reserve stem cells, can survive and quickly rebuild intestinal tissues. The findings align with observations by oncologists that short-term fasting prior to chemotherapy can mitigate the severity of gastrointestinal destruction.
Christopher Lengner, an associate professor in Penn’s School of Veterinary Medicine collaborated on the work with lead author Maryam Yousefi, a graduate student in the Cell and Molecular Biology program at Penn Medicine and a Howard Hughes Medical Institute International Student Fellow, and other colleagues from Penn and China Agricultural University. Their work appears in the journal Stem Cell Reports.
One theory has been that calorie restriction slows age-related degeneration and enables more efficient tissue function by influencing the integrity and activity of adult stem cells, the precursor cells that dwell within specific tissues and give rise to the diversity of cell types that compose that tissue.
In prior work, Lengner’s lab has studied how certain stem cells in the intestines resist DNA damage. Perhaps, the researchers reasoned, calorie restriction is somehow targeting these stem cells to enhance their ability to resist damage.
Recent studies focused on the effects of calorie restriction on the active intestinal stem cells. While these active stem cells bear the burden of daily tissue turnover and act as the workhorses of intestinal function, they are also known to be highly susceptible to DNA damage, such as that induced by radiation exposure, and thus are unlikely to be the cells mediating the enhanced regeneration seen under calorie restriction, the Penn team reasoned.
Instead of looking at these active stem cells, Lengner’s group examined a second population of intestinal stem cells known as reserve stem cells. Lengner’s group and others had previously shown that these reserve stem cells normally reside in a dormant state and are protected from chemotherapy and radiation. Upon a strong injury that kills the active cells, these reserve stem cells “wake up” to regenerate the tissue.
To investigate this hypothesis, the scientists focused on how a subpopulation of mouse intestinal stem cells responded under calorie restriction and then when the animals were exposed to radiation. When mice were fed a diet reduced in calories by 40 percent from normal, the researchers observed that reserve intestinal stem cells expanded five-fold. Paradoxically, these cells also seemed to divide less frequently, a mystery the researchers hope to follow up on in later work.
When the research team selectively deleted the reserve stem cells in calorie-restricted mice, their intestinal tissue’s regeneration capabilities were cut in half, implicating these cells as having an important role in carrying out the benefits of calorie restriction.
“These reserve stem cells are rare cells,” Lengner said. “In a normal animal they may make up less than half a percentage of the intestinal epithelium and in calorie restricted animals maybe slightly more. Normally, in the absence of injury, the tissue can tolerate the loss, due to the presence of the active stem cells, but, when you injure the animal, the regeneration is compromised and the enhanced regeneration after calorie restriction was compromised in the absence of the reserve stem cell pool.”
To tease out the mechanism by which these cells were acting, the researchers compared the genes that were turned on in normal versus calorie-restricted animals. “It was very obvious,” Lengner said. “These reserve stem cells that we had shown were important for the beneficial effects of calorie restriction, were repressing many pathways that are all known to be regulated by the protein complex mTOR, which is most well known as being a nutrient-sensing complex.”
The finding made intuitive sense; researchers studying other tissue types had shown that activating mTOR can drive dormant cells out of quiescence, a necessary step for regeneration. Here, researchers found that reserve stem cells had low mTOR activity, and this was even lower upon calorie restriction. Lower mTOR activity correlated with resistance to injury. Yet in order to regenerate after the injury was over, these cells would need mTOR again.
“Curiously, we see that, when they’re injured, the calorie-restricted mice were actually better able to activate mTOR than their counterparts,” Lengner said. “So somehow, even though mTOR is being suppressed initially, it’s also better poised to become activated after injury. That’s something we don’t fully understand.”
The researchers, led by Yousefi, conducted experiments using leucine, an amino acid that activates mTOR, and rapamycin, a drug -which inhibits mTOR, to confirm that mTOR acted within these reserve stem cells to regulate their activity. Reserve stem cells exposed to leucine proliferated, while those exposed to rapamycin were blocked.
Pretreating the animals with leucine make the reserve stem cells more sensitive to radiation and less able to regenerate tissue following radiation injury, while rapamycin protected the reserve stem cells as they were more likely to remain dormant.
Lengner cautions, however, that rapamycin cannot be used as a stand-in for calorie restriction, as it would linger and continue to block mTOR activation even following injury, hindering the ability of the reserve stem cells to spring into action and regenerate intestinal tissue.
In future work, the researchers hope to drill down deeper, looking beyond nutrient signaling to see what type of signaling molecules can modulate the activation of reserve stem cells.
Research funding: Howard Hughes Medical Institute, National Natural Science Foundation of China, National Institute of Diabetes and Digestive and Kidney Diseases, National Cancer Institute, and Center for Molecular Studies in Digestive and Liver Diseases.
An international team of researchers from various academic institutions and NASA Ames Research Center have published a roadmap toward enhancing human radioresistance in the peer-reviewed journal Oncotarget. This is important as our interest in space exploration and colonization is increasing and therefore, research into methods of enhancing radioresistance to protect against the various forms of space radiation that spacefarers would be subjected to needs to be accelerated accordingly. In addition researchers believe that research into radioresistance would also promote healthspan extension.
Strategies for radioresistance. Credit: Biogerontology Research Foundation and other institutions mentioned below.
The roadmap outlines future research directions toward the goal of enhancing human radioresistance, including up regulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, the coordination of regenerative and ablative technologies, and methods of slowing metabolic activity while preserving cognitive function. The paper concludes by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well.
The roadmap highlights the need to converge and accelerate research in radiobiology, biogerontology and artifical intelligence to enable spacefarers to address both the healthcare challenges that we are already aware of, as well as those that we are not.
Furthermore, given the massive amount of funding allocated to research into facilitating and optimizing space exploration and optimization, the researchers hope to have shown how research into enhancing radioresistance for space exploration could galvanize progress in human healthspan extension, an area of research that is still massively underfunded despite its potential to prevent the massive economic burden posed by the future healthcare costs associated with demographic aging.
Participating institutions: NASA Ames Research Center, Environmental and Radiation Health Sciences Directorate at Health Canada, Oxford University, Canadian Nuclear Laboratories, Belgian Nuclear Research Centre, Insilico Medicine, the Biogerontology Research Center, Boston University, Johns Hopkins University, University of Lethbridge, Ghent University, and Center for Healthy Aging.
Citation: Cortese, Franco, Dmitry Klokov, Andreyan Osipov, Jakub Stefaniak, Alexey Moskalev, Jane Schastnaya, Charles Cantor, Alexander Aliper, Polina Mamoshina, Igor Ushakov, Alex Sapetsky, Quentin Vanhaelen, Irina Alchinova, Mikhail Karganov, Olga Kovalchuk, Ruth Wilkins, Andrey Shtemberg, Marjan Moreels, Sarah Baatout, Evgeny Izumchenko, João Pedro De Magalhães, Artem V. Artemov, Sylvain V. Costes, Afshin Beheshti, Xiao Wen Mao, Michael J. Pecaut, Dmitry Kaminskiy, Ivan V. Ozerov, Morten Scheibye-Knudsen, and Alex Zhavoronkov. “Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization.” Oncotarget, 2015. doi:10.18632/oncotarget.24461.
A recent study, led by an international team of researchers confirms that targeted removal of senescent cells (SnCs), accumulated in many vertebrate tissues as we age, contribute significantly in delaying the onset of age-related pathologies.
Credit: Baker et al., Nature
This breakthrough research has been led by Dr. Chaekyu Kim and Dr. Ok Hee Jeon. In the study, the research team presented a novel pharmacologic candidate that alleviates age-related degenerative joint conditions, such as osteoarthritis (OA) by selectively destroying SnCs. Their findings, published in Nature Medicine, suggest that the selective removal of old cells from joints could reduce the development of post-traumatic OA and allow new cartilage to grow and repair joints.
To test the idea that SnCs might play a causative role in OA, the research team took both younger and older mice and cut their anterior cruciate ligaments (ACL) to minic injury. They, then, administered injections of an experimental drug, named UBX0101 to selectively remove SnCs after anterior cruciate ligament transection (ACLT) surgery.
Preclinical studies in mice and human cells suggested that the removal of SnCs significantly reduced the development of post-traumatic OA and related pain and created a prochondrogenic environment for new cartilage to grow and repair joints. Indeed, the research team reported that aged mice did not exhibit signs of cartilage regeneration after treatment with UBX0101 injections,
According to the research team, the relevance of their findings to human disease was validated using chondrocytes isolated from arthritic patients. The research team notes that their findings provide new insights into therapies targeting SnCs for the treatment of trauma and age-related degenerative joint disease.
Citation: Jeon, Ok Hee, Chaekyu Kim, Remi-Martin Laberge, Marco Demaria, Sona Rathod, Alain P. Vasserot, Jae Wook Chung, Do Hun Kim, Yan Poon, Nathaniel David, Darren J. Baker, Jan M Van Deursen, Judith Campisi, and Jennifer H. Elisseeff. “Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment.” Nature Medicine 23, no. 6 (2017): 775-81. doi:10.1038/nm.4324. Adapted from press release by the Uslan National Institute of Science and Technology.
The study, led by scientists from Imperial College London in collaboration with the World Health Organization, analyzed long-term data on mortality and longevity trends to predict how life expectancy will change in 35 industrialized countries by 2030. Nations in the study included both high-income countries, such as the USA, Canada, UK, Germany, Australia, and emerging economies such as Poland, Mexico, and the Czech Republic. The researchers chose countries in the study as they all had reliable data on deaths since at least 1985.
Posterior distribution of projected change in life expectancy at birth from 2010 to 2030. Credit: The Lancet.
The study, published in The Lancet and funded by the UK Medical Research Council, revealed all nations in the study can expect to see an increase in life expectancy by 2030. The results also found that South Koreans may have the highest life expectancy in the world in 2030. The UK’s average life expectancy at birth for women will be 85.3 years in 2030.
Professor Ezzati, lead researcher from the School of Public Health at Imperial explained that South Korea’s high life expectancy may be due to a number of factors including good nutrition in childhood, low blood pressure, low levels of smoking, good access to healthcare, and uptake of new medical knowledge and technologies.
French women and Swiss men were predicted to have the highest life expectancies at birth in Europe in 2030, with an average life expectancy of 88.6 years for French women and nearly 84 years for Swiss men.
The results also revealed that the USA is likely to have the lowest life expectancy at birth in 2030 among high-income countries. The nation’s average life expectancy at birth of men and women in 2030 (79.5 years and 83.3 years), will be similar to that of middle-income countries like Croatia and Mexico. The research team thinks this may be due to a number of factors including a lack of universal healthcare, as well as the highest child and maternal mortality rate, homicide rate and obesity among high-income countries.
Along with the US, other countries who may see only small increases in life expectancy by 2030 included Japan, Sweden, and Greece, while Macedonia and Serbia were projected to have the lowest life expectancies at birth for women and men respectively in 2030.
The UK’s average life expectancy at birth for women will be 85.3 years in 2030. This places them at 21st in the table of 35 countries. The average life expectancy of a UK man meanwhile will be 82.5 years in 2030. This places them at 14th in the table of 35 countries.
The research also suggested the gap in life expectancy between women and men is closing. Professor Ezzati explained: “Men traditionally had unhealthier lifestyles and so shorter life expectancies. They smoked and drank more, and had more road traffic accidents and homicides. However as lifestyles become more similar between men and women, so does their longevity.”
Professor Colin Mathers, co-author from the World Health Organization explained: “The increase in average life expectancy in high-income countries is due to the over-65s living longer than ever before. In middle-income countries, the number of premature deaths – i.e. people dying in their forties and fifties, will also decline by 2030.” The team developed a new method to predict longevity, similar to the methods used for weather forecasting, which takes into account numerous different models for forecasting mortality and life expectancy.
Life expectancy is calculated by assessing the age at which people die across the whole population. For instance, if a country has high childhood mortality rate, this will make average national life expectancy much lower, as would a country in which many young people die of injuries and violence. The team developed a new method to predict longevity, similar to the methods used for weather forecasting, which takes into account numerous different models for forecasting mortality and life expectancy. All the predictions in the study come with some uncertainty range.
Professor Ezzati added that these results suggest we need to be thinking carefully about the needs of an ageing population: “The fact that we will continue to live longer means we need to think about strengthening the health and social care systems to support an ageing population with multiple health needs. This is the opposite of what is being done in the era of austerity. We also need to think about whether current pension systems will support us, or if we need to consider working into later life.”
Citation: Kontis, Vasilis, James E Bennett, Colin D Mathers, Guangquan Li, Kyle Foreman, and Majid Ezzati. 2017. “Future Life Expectancy in 35 Industrialised Countries: Projections with a Bayesian Model Ensemble.” The Lancet, February. Elsevier. doi:10.1016/S0140-6736(16)32381-9. Research funding: UK Medical Research Council, US Environmental Protection Agency. Adapted from press release by Imperial College London.
Recent research published in Molecular & Cellular Proteomics offers one glimpse into how cutting calories impacts aging inside a cell. The researchers found that when ribosomes – the cell’s protein makers – slow down, the aging process slows too. The decreased speed lowers production but gives ribosomes extra time to repair themselves. Repairing individual parts of the ribosome on a regular basis enables ribosomes to continue producing high-quality proteins for longer than they would otherwise.
“The ribosome is a very complex machine, sort of like your car, and it periodically needs maintenance to replace the parts that wear out the fastest,” said Brigham Young University biochemistry professor and senior author John Price.
“When tires wear out, you don’t throw the whole car away and buy new ones. It’s cheaper to replace the tires.” So what causes ribosome production to slow down in the first place? At least for mice: reduced calorie consumption.
Price and his fellow researchers observed two groups of mice. One group had unlimited access to food while the other was restricted to consume 35 percent fewer calories, though still receiving all the necessary nutrients for survival. “The calorie-restricted mice are more energetic and suffered fewer diseases,” Price said. “And it’s not just that they’re living longer, but because they’re better at maintaining their bodies, they’re younger for longer as well.”
Despite this study’s observed connection between consuming fewer calories and improved lifespan, Price assured that people shouldn’t start counting calories and expect to stay forever young. Calorie restriction has not been tested in humans as an anti-aging strategy, and the essential message is understanding the importance of taking care of our bodies.
Citation: Mathis, Andrew D., Bradley C. Naylor, Richard H. Carson, Eric Evans, Justin Harwell, Jared Knecht, Eric Hexem, Fredrick F. Peelor, Benjamin F. Miller, Karyn L. Hamilton, Mark K. Transtrum, Benjamin T. Bikman, and John C. Price. “Mechanisms of In Vivo Ribosome Maintenance Change in Response to Nutrient Signals.” Molecular & Cellular Proteomics 16, no. 2 (2016): 243-54. doi:10.1074/mcp.m116.063255 Adapted from press release by Brigham Young University.
According to a new study by Université de Montréal’s School of Speech-Language Pathology and Audiology, part of UdeM’s medical faculty learning to play musical instrument help elderly to react faster and to stay alerted. The study is published in journal Brain and Cognition. The study shows that musicians have faster reaction times to sensory stimuli than non-musicians have.
According to lead researcher Simon Landry, this study has implications for preventing some effects of aging. “The more we know about the impact of music on really basic sensory processes, the more we can apply musical training to individuals who might have slower reaction times,” Landry said.
In his study, co-authored with his thesis advisor, audiology associate professor François Champoux, Landry compared the reaction times of 16 musicians and 19 non-musicians. Research subjects sat in a quiet, well-lit room with one hand on a computer mouse and the index finger of the other on a vibrotactile device, a small box that vibrated intermittently. They were told to click on the mouse when they heard a sound (a burst of white noise) from the speakers in front of them, or when the box vibrated, or when both happened.
Each of the three stimulations – audio, tactile and audio-tactile – was done 180 times. The subjects wore earplugs to mask any buzzing “audio clue” when the box vibrated. “We found significantly faster reaction times with musicians for auditory, tactile and audio-tactile stimulations,” Landry writes in his study.
“These results suggest for the first time that long-term musical training reduces simple non-musical auditory, tactile and multisensory reaction times.” The musicians were recruited from UdeM’s music faculty, started playing between ages 3 and 10, and had at least seven years of training. There were eight pianists, 3 violinists, two percussionists, one double bassist, one harpist and one viola player. All but one (a violinist) also mastered a second instrument or more. The non-musicians were students at the School of Speech-Language Pathology. As with the musicians, roughly half were undergraduates and half graduates.
Landry, whose research interest is in how sound and touch interact, said his study adds to previous ones that looked at how musicians’ brains process sensory illusions. “The idea is to better understand how playing a musical instrument affects the senses in a way that is not related to music,” he said of his study.
Citation: Landry, Simon P., and François Champoux. “Musicians react faster and are better multisensory integrators.” Brain and Cognition 111 (2017): 156-162. DOI: 10.1016/j.bandc.2016.12.001 Research funding: Canadian Institutes of Health Research, Fonds de recherche Québec – Santé, and Natural Sciences and Engineering Research Council of Canada. Adapted from press release by the Université de Montréal.
Ever since researchers connected the shortening of telomeres the protective structures on the ends of chromosomes to aging and disease, the race has been on to understand the factors that govern telomere length. Now, Scientists at the Salk Institute have found that a balance of elongation and trimming in stem cells results in telomeres that are not too short and not too long, but just right.
Immunofluorescence analysis of pluripotent markers Nanog (red) and TRA-1-60 (green) in human induced pluripotent stem cells derived from skin fibroblasts. DNA is shown in blue. Credit: Salk Institute.
“This work shows that the optimal length for telomeres is a carefully regulated range between two extremes,” says Jan Karlseder, a professor in Salk’s Molecular and Cell Biology Laboratory and senior author of the work. “It was known that very short telomeres cause harm to a cell. But what was totally unexpected was our finding that damage also occurs when telomeres are very long.”
Karlseder, Rivera, and colleagues began by investigating telomere maintenance in laboratory-cultured lines of human embryonic stem cells (ESCs). Using molecular techniques, they varied telomerase activity. Perhaps not surprisingly, cells with too little telomerase had very short telomeres and eventually the cells died. Conversely, cells with augmented levels of telomerase had very long telomeres. But instead of these cells thriving, their telomeres developed instabilities.
The team observed that very long telomeres activated trimming mechanisms controlled by a pair of proteins called XRCC3 and Nbs1. The lab’s experiments show that reduced expression of these proteins in ESCs prevented telomere trimming, confirming that XRCC3 and Nbs1 are indeed responsible for that task.
Next, the team looked at induced pluripotent stem cells (iPSCs), which are differentiated cells (e.g., skin cells) that are reprogrammed back to a stem-cell-like state. They looked at induced pluripotent stem cells (iPSCs) because they can be genetically matched to donors and are easily obtainable–are common and crucial tools for potential stem cell therapies. The researchers discovered that induced pluripotent stem cells (iPSCs) contain markers of telomere trimming, making their presence a useful gauge of how successfully a cell has been reprogrammed.
“Stem cell reprogramming is a major scientific breakthrough, but the methods are still being perfected. Understanding how telomere length is regulated is an important step toward realizing the promise of stem cell therapies and regenerative medicine,” says Rivera.
Citation: Rivera, Teresa, Candy Haggblom, Sandro Cosconati, and Jan Karlseder. “A balance between elongation and trimming regulates telomere stability in stem cells.” Nature Structural & Molecular Biology (2016). DOI: 10.1038/nsmb.3335 Adapted from press release by Salk Institute.
Researchers from UCLA and Caltech have made discoveries that might help slow and potentially reverse the process of aging in cells. They generated new methods that allow identification of factors that selectively remove damaged mitochondrial DNA, which will affect the process of aging at the cellular level. Aging is, in part, due to changes in mitochondria, the energy-providing powerhouses of the cell. Mitochondria contain their own DNA, and the accumulation of mutations of mitochondrial DNA throughout a lifetime contributes to aging.
There are two strategies for combating age-related diseases. One way is to fight the individual disease. The other aims to delay the aging process to prevent or delay the onset of age-related diseases in general.
Mitochondria provide most of the energy for cellular operations. Cumulative damage to mitochondrial DNA contributes to age-related disorders such as Parkinson’s disease, Alzheimer’s disease, heart disease, and muscle wasting and frailty. One key goal to delay or reverse aging is to reduce the ratio of damaged to normal mitochondrial DNA. Inherited defects in mitochondrial DNA also cause a number of devastating childhood diseases, including strokes and muscle diseases.
“We showed that we could selectively cleanse the damaged mitochondrial DNA, effectively rejuvenating them and improving mitochondrial quality,” said Ming Guo, P. Gene & Elaine Smith Chair in Alzheimer’s Disease Research, and professor of neurology & pharmacology at David Geffen School of Medicine at UCLA. “This strategy might someday prove useful in treating or preventing age-related diseases as well as the general declines in cognitive function and mobility that occur with aging.”
The researchers found that by activating cellular processes known as “autophagy,” it was possible to remove 95 percent of the damaged mitochondrial DNA. In addition, Guo’s team found that activation of pathways that are crucial in preventing Parkinson’s disease also dramatically cleansed damaged mitochondrial DNA.
Studying the role that these DNA mutations have in disease hasn’t been easy, in part because of the lack of good laboratory models.
For the study, which appeared in Nature Communications on Nov. 14, Guo and her laboratory teamed up with the lab of Bruce Hay, professor of biology and biological engineering at Caltech, to create a model of mitochondrial DNA using the fruit fly Drosophila. The findings demonstrate that the level of damaged mitochondrial DNA can be reduced in cells simply by boosting the body’s natural quality control processes. “From our results it appears that this process is normally present, but not very efficient,” Guo said. “We can enhance mitochondrial quality by stimulating certain cellular processes.”
Guo and Hay now plan to use the model to screen for potential drugs that have a similar impact — drugs that might rejuvenate mitochondria to improve overall cellular health. “One can envision undergoing periodic cellular ‘house cleaning’ to reverse mitochondrial damages from muscle, the brain and other tissues to maintain cognitive function and mobility, and promote healthy aging,” Guo said. “We want to keep our fabulous mitochondria to dial back the aging clock.”
Citation: Kandul, Nikolay P., Ting Zhang, Bruce A. Hay, and Ming Guo. “Selective removal of deletion-bearing mitochondrial DNA in heteroplasmic Drosophila.” Nature Communications 7 (2016): 13100. DOI: http://dx.doi.org/10.1038/ncomms13100 Research funding: National Institutes of Health, Kenneth Glenn Family Foundation, Natalie R. and Eugene S. Jones Fund in Aging and Neurodegenerative Disease Research, and Ellison Medical Foundation Senior Scholar Award. Adapted from press release by University of California Los Angeles
Today the Biogerontology Research Foundation announced the international collaboration on signaling pathway perturbation-based transcriptomic biomarkers of aging. On November 16th scientists at the Biogerontology Research Foundation alongside collaborators from Insilico Medicine, Inc, the Johns Hopkins University, Albert Einstein College of Medicine, Boston University, Novartis, Nestle and BioTime Inc. announced the publication of their proof of concept experiment demonstrating the utility of a novel approach for analyzing transcriptomic, metabolomic and signalomic data sets, titled iPANDA,in Nature Communications.
“Given the high volume of data being generated in the life sciences, there is a huge need for tools that make sense of that data. As such, this new method will have widespread applications in unraveling the molecular basis of age-related diseases and in revealing biomarkers that can be used in research and in clinical settings. In addition, tools that help reduce the complexity of biology and identify important players in disease processes are vital not only to better understand the underlying mechanisms of age-related disease but also to facilitate a personalized medicine approach. The future of medicine is in targeting diseases in a more specific and personalized fashion to improve clinical outcomes, and tools like iPANDA are essential for this emerging paradigm,” said João Pedro de Magalhães, PhD, a trustee of the Biogerontology Research Foundation.
The algorithm, iPANDA, applies deep learning algorithms to complex gene expression data sets and signal pathway activation data for the purposes of analysis and integration, and their proof of concept article demonstrates that the system is capable of significantly reducing noise and dimensionality of transcriptomic data sets and of identifying patient-specific pathway signatures associated with breast cancer patients that characterize their response to Toxicol-based neoadjuvant therapy.
The system represents a substantially new approach to the analysis of microarray data sets, especially as it pertains to data obtained from multiple sources, and appears to be more scalable and robust than other current approaches to the analysis of transcriptomic, metabolomic and signalomic data obtained from different sources. The system also has applications in rapid biomarker development and drug discovery, discrimination between distinct biological and clinical conditions, and the identification of functional pathways relevant to disease diagnosis and treatment, and ultimately in the development of personalized treatments for age-related diseases.
While the team predicted and compared the response of breast cancer patients to Taxol-based neoadjuvant therapy as their proof of concept, the application of this approach to patient-specific responses to biomedical gerontological interventions (e.g. to geroprotectors, which is a clear focus of the team’s past efforts), to the development of both generalized and personalized biomarkers of ageging, and to the characterization and analysis of minute differences in ageging over time, between individuals, and between different organisms would represent a promising and exciting future application” said Franco Cortese, Deputy Director of the Biogerontology Research Foundation.
Citation: “In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development”. Ivan V. Ozerov, Ksenia V. Lezhnina, Evgeny Izumchenko, Artem V. Artemov, Sergey Medintsev, Quentin Vanhaelen, Alexander Aliper, Jan Vijg, Andreyan N. Osipov, Ivan Labat, Michael D. West, Anton Buzdin, Charles R. Cantor, Yuri Nikolsky, Nikolay Borisov, Irina Irincheeva, Edward Khokhlovich, David Sidransky, Miguel Luiz Camargo & Alex Zhavoronkov. Nature Communications 2016 vol: 7 pp: 13427. DOI: http://dx.doi.org/10.1038/NCOMMS13427 Adapted from press release by Biogerontology Research Foundation