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Category: life extension – Page 419
Aubrey de Grey, Ph.D., Vice President of New Technology Discovery for AgeX Therapeutics, discusses how primitive organisms have better regenerative capacity than more complicated organisms such as humans. In humans, Dr. de Grey notes, our best regenerative abilities are at the embryonic stage. During the Embryonic Fetal Transition, out ability to regenerate plummets and continues to diminish as we age. Dr. de Grey discusses the role evolution plays in this and how scientists may be able to “revive” our regenerative power. This video is part of a series from AgeX on research into aging and human longevity. For more information on Agex Therapeutics, please visit http://www.agexinc.com.
Artificial intelligence (AI) has emerged as a powerful approach for integrated analysis of the rapidly growing volume of multi-omics data, including many research and clinical tasks such as prediction of disease risk and identification of potential therapeutic targets. However, the potential for AI to facilitate the identification of factors contributing to human exceptional health and life span and their translation into novel interventions for enhancing health and life span has not yet been realized. As researchers on aging acquire large scale data both in human cohorts and model organisms, emerging opportunities exist for the application of AI approaches to untangle the complex physiologic process(es) that modulate health and life span. It is expected that efficient and novel data mining tools that could unravel molecular mechanisms and causal pathways associated with exceptional health and life span could accelerate the discovery of novel therapeutics for healthy aging. Keeping this in mind, the National Institute on Aging (NIA) convened an interdisciplinary workshop titled “Contributions of Artificial Intelligence to Research on Determinants and Modulation of Health Span and Life Span” in August 2018. The workshop involved experts in the fields of aging, comparative biology, cardiology, cancer, and computational science/AI who brainstormed ideas on how AI can be leveraged for the analyses of large-scale data sets from human epidemiological studies and animal/model organisms to close the current knowledge gaps in processes that drive exceptional life and health span. This report summarizes the discussions and recommendations from the workshop on future application of AI approaches to advance our understanding of human health and life span.
Aging is often described as the outcome of interactions among genetic, environmental and lifestyle factors with wide variation in life and health span between and within species (Newman and Murabito, 2013; Partridge et al., 2018; Singh et al., 2019). Exceptional life and health span represents an extreme phenotype characterized by exceptional survival (well-beyond average life expectancy), delayed onset of age-related diseases (before 80 years of age) (Pignolo, 2019) and/or preservation of good health/function relative to their peers (Perls et al., 2000, 2002; Kaeberlein, 2018). The identification of SNP associations with exceptional life and health span is a starting point for identifying targets for interventions that could potentially promote healthy human aging.
The pursuit of longevity has been the goal of humanity since ancient times. Genetic alterations have been demonstrated to affect lifespan. As increasing numbers of pro-longevity genes and anti-longevity genes have been discovered in Drosophila, screening for functionally important genes among the large number of genes has become difficult. The aim of the present study was to explore critical genes and pathways affecting longevity in Drosophila melanogaster. In this study, 168 genes associated with longevity in D. melanogaster were collected from the Human Ageing Genomic Resources (HAGR) database. Network clustering analysis, network topological analysis, and pathway analysis were integrated to identify key genes and pathways. Quantitative real-time PCR (qRT-PCR) was applied to verify the expression of genes in representative pathways and of predicted genes derived from the gene–gene sub-network. Our results revealed that six key pathways might be associated with longevity, including the longevity-regulating pathway, the peroxisome pathway, the mTOR-signalling pathway, the FOXO-signalling pathway, the AGE-RAGE-signalling pathway in diabetic complications, and the TGF-beta-signalling pathway. Moreover, the results revealed that six key genes in representative pathways, including Cat, Ry, S6k, Sod, Tor, and Tsc1, and the predicted genes Jra, Kay, and Rheb exhibited significant expression changes in ageing D. melanogaster strain w1118 compared to young ones. Overall, our results revealed that six pathways and six key genes might play pivotal roles in regulating longevity, and three interacting genes might be implicated in longevity. The results will not only provide new insight into the mechanisms of longevity, but also provide novel ideas for network-based approaches for longevity-related research.
We recently had the opportunity to catch up with Sarah Constantin, one of the founders of the new biotech startup company Daphnia Labs. The company is developing a new platform for the discovery of geroprotective drugs: in vivo phenotypic screens in model organisms. The company plans to use high-resolution video to track Daphnia during its lifespan in order to screen for drugs that might extend healthspan.
Can you tell us a little about the company, its founders, and what motivated you to start this biotech company?
I’d been working for about a year at the Longevity Research Institute, which is a nonprofit that funds aging research. LRI focuses on trying to replicate studies on interventions that have been reported to extend lifespan in mammals. Basically, of the 50+ compounds out there that have some mammalian evidence for an anti-aging effect, which ones have the best chance of being viable geroprotectors in humans?
Bill Faloon, Director / Co-Founder of Life Extension Foundation — ideaXme Show — Ira Pastor
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The black mouse on the screen sprawls on its belly, back hunched, blinking but otherwise motionless. Its organs are failing. It appears to be days away from death. It has progeria, a disease of accelerated aging, caused by a genetic mutation. It is only three months old.
I am in the laboratory of Juan Carlos Izpisúa Belmonte, a Spaniard who works at the Gene Expression Laboratory at San Diego’s Salk Institute for Biological Studies, and who next shows me something hard to believe. It’s the same mouse, lively and active, after being treated with an age-reversal mixture. “It completely rejuvenates,” Izpisúa Belmonte tells me with a mischievous grin. “If you look inside, obviously, all the organs, all the cells are younger.”
Izpisúa Belmonte, a shrewd and soft-spoken scientist, has access to an inconceivable power. These mice, it seems, have sipped from a fountain of youth. Izpisúa Belmonte can rejuvenate aging, dying animals. He can rewind time. But just as quickly as he blows my mind, he puts a damper on the excitement. So potent was the rejuvenating treatment used on the mice that they either died after three or four days from cell malfunction or developed tumors that killed them later. An overdose of youth, you could call it.
Ira Pastor, ideaXme longevity and aging Ambassador and Founder of Bioquark interviews Bill Faloon, Director and Co-Founder, Life Extension Foundation and Founder of The Church Of Perpetual Life.
Ira Pastor Comments:
On the last several shows we have spent time on different hierarchical levels the biologic-architecture of the life, disease and aging process. We’ve spent some time talking about the genome, the microbiome, tissue engineering, systems biology, and dabbled a bit in the areas of quantum biology, organism hydro-dynamics, and even chronobiology.
As exciting and promising as all these research paths are, at the end of the day, in order for them to yield what many people are looking for, that is radically extended healthspans and lifespans, there needs to be an organized system of human translation build around them, integrating these various products, services and technologies, from supplements, to biologics, to functional foods, to cosmeceuticals, to various physio-therapeutic interventions, and so forth, as well as all the related supporting advocacy and education, as biologic aging is truly a multi-factorial, combinatorial process that is never going to be amenable to big pharma’s traditional “single magic bullet” philosophy that it promoted throughout the last century.
For today’s guest, I could think of no one better to talk with us about this topic and take us into the future on this front, than Bill Faloon, Director and Co-Founder, Life Extension Foundation (LEF), a consumer advocacy organization with over 100,000 members that funds research (investing million per year in researchers around the globe) and disseminates information to consumers about optimal health, and more recently in the area of actionable clinical interventions regarding human biologic age reversal, through a fascinating new project called the Age Reversal Network, defined as an open-source communications channel to exchange scientific information, foster strategic alliances, and support biomedical endeavors aimed at reversing degenerative aging.
Bill is also the Founder of The Church Of Perpetual Life, a nonprofit transhumanist organization aiming to combine discussion integrating spirituality, community, and aging scientific research in a single unified forum.
He’s a board member of the Coalition For Radical Life Extension, which is the organizer of annual RAADfest conference (Revolution Against Aging and Death) which is the world’s largest gathering of radical life extension enthusiasts.
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Well, that depends on your frame of reference, but even so, does that mean that we need to stop worrying about aging? Not really.
In addition to having access to large colonies of monkeys and other species, animal researchers in China face less public scrutiny than counterparts in the United States and Europe. Ji, who says his primate facility follows international ethical standards for animal care and use, notes that the Chinese public has long supported monkey research to help human health. “Our religion or our culture is different from that of the Western world,” he says. Yet he also recognizes that opinions in China are evolving. Before long, he says, “We’ll have the same situation as the Western world, and people will start to argue about why we’re using a monkey to do an experiment because the monkey is too smart, like human beings.”
This story, one in a series, was supported by the Pulitzer Center.
BEIJING, GUANGZHOU, JIANGMEN, KUNMING, AND SHANGHAI—Early one February morning, researchers harvest six eggs from a female rhesus macaque—one of 4000 monkeys chirping and clucking in a massive outdoor complex of metal cages here at the Yunnan Key Laboratory of Primate Biomedical Research. On today’s agenda at the busy facility, outside Kunming in southwest China: making monkey embryos with a gene mutated so that when the animals are born 5 months later, they will age unusually fast. The researchers first move the eggs to a laboratory bathed in red light to protect the fragile cells. Using high-powered microscopes, they examine the freshly gathered eggs and prepare to inject a single rhesus sperm into each one. If all goes well, the team will introduce the genome editor CRISPR before the resulting embryo begins to grow—early enough for the mutation for aging to show up in all cells of any offspring.
But as often happens when eggs are retrieved, all does not go well. Only one egg in this morning’s batch is mature enough to fertilize. “We were a little unlucky today,” says Niu Yuyu, who with facility director Ji Weizhi runs the gene-editing research. The group can afford a little bad luck, though. Through a combination of patience, ingenuity, and enormous animal resources, the team has already used CRISPR to create an astonishing range of genome-edited monkeys to serve as models for studying human diseases.