Reversing The Aging Clock With Epigenetic Reprogramming – Bio-IT World
By daniellenierenberg
By Deborah Borfitz
January 13, 2021 | As aging researchers are aware, birthday candles are not a good guide to either human health or longevity. But there is an abundance of clues in the genome and, as suggested by studies in animals, some of age-related damage is reversible by removing or reprogramming problematic cells or blocking the activity of key proteins.
As it turns out, DNA methylationa frequently-used biomarker of biological ageis not just marking time like a clock on the wall but actually controlling time within cells, according to David Sinclair, an expert on aging at Harvard Medical School and cofounder of 4-year-old Life Biosciences. The revelation emerged from a study recently published in Nature (DOI: 10.1038/s41586-020-2975-4) where Harvard researchers showed, for the first time, that the pattern of DNA methylation in the genome can be safely reset to a younger age.
It was in fact a prerequisite to restoring youthful function and vision in old mice, says Sinclair, who has spent most of his adult life studying the epigenetic changes associated with aging. Up until a few years ago, he thought the process was unidirectional and that cells ultimately lost their identity and malfunctioned or became cancerous.
It seemed crazy to try to get proteins to return to the place they were in young cells, Sinclair says. Proteins move around in response to age-associated DNA damage and end up in the wrong places on the genome, causing the wrong genes to be turned on, but scientists did not know if proteins could go back, where the instructions were stored, or if they were being stored at all.
As covered in his 2019 bestseller Lifespan, Sinclair now believes that aging is the result of the so-called epigenetic changes scrambling how the body reads genetic code. Were essentially looking for the polish to get the cell to read the genome correctly again, he says, a process he likens to recovering music on a scratched CD.
Yamanaka Factors
Sinclair and his research associates have been focusing on the eye, in part because retinal tissues start aging soon after birth, he explains. While a damaged optic nerve can heal in a newborn, the injury is irreversible in a 1-year-old.
Yuancheng Lu, a former student of Sinclairs, was also interested in the eye because his family has a vision-correction business and recognized sight loss as a huge unmet need, he continues. We thought if we could take the age of those retinal cells back far enough, but not so far that they lose their identity, we might be able to see regrowth of the optic nerve if it was damaged.
Among the foundational work was a 2016 study in Cell (DOI: 10.1016/j.cell.2016.11.052) by Life Biosciences cofounder Juan Carlos Izpisua Belmonte (Salk Institute for Biological Studies) who partially erased cellular markers of aging in mice that aged prematurely, as well as in human cells, by turning on Yamanaka factors Oct4, Sox2, Klf4, and c-Myc (OSKM) highly expressed in embryonic stem cells. Short-term induction of OSKM ameliorated hallmarks of aging and modestly extended lifespan in the short-lived mice.
The lifespan gain was widely dismissed as an artifact of shocking a mouse, says Sinclair, since the mice died if the treatment continued for more than two days. Although the human health implications appeared unlikely, his Harvard team decided to try the approach using an adeno-associated virus as a vehicle to deliver the youth-restoring OSKM genes into the retinas of aging mice.
The technology kept killing the mice or causing them to get cancer until Lu decided to drop the c-Myc genean oncogenein his experiments using human skin cells. He looked at [damaged] cells that had been expressing OSK for three weeks and the nerves were growing back toward the brain to an unprecedented degree. Moreover, the cells got older by the damage and younger by the treatment.
As the broader team went on to show in the Nature paper, the trio of Yamanaka factors effectively made cells younger without causing them to lose their identity (i.e., turning back into induced pluripotent stem cells) or fueling tumor growth even after a year of continuous treatment of the entire body of a mouse. If anything, the mice had fewer tumors over the course of the study, says Sinclair.
Although the mice needed to be autopsied to definitively measure tumor burden, Sinclair says the study will be repeated to learn if the epigenetic reprogramming technique can increase lifespan.
Findings have implications beyond the treatment of age-related diseases specific to the eye, says Sinclair. Aging researchers have published studies showing other types of tissues, including muscle and kidney cells, can also be rejuvenated.
Clocked Results
In the latest study using mice, epigenetic reprogramming was found to have three beneficial effects on the eye: promotion of optic nerve regeneration, reversal of vision loss with a condition mimicking human glaucoma, and reversal of vision loss in aging animals without glaucoma. The latter finding, from Sinclairs vantage point, is the most important one. This is ultimately a story about finding a repository of youthful information in old cells that can reverse aging.
Results of all three experiments are noteworthy and have commonly thought to be three separate processes, says Sinclair. That is only because the fields of aging and acute and chronic disease are distinct disciplines that rarely talk to each other.
The Harvard team is pioneering a new way to tackle diseases of aging by addressing the underlying cause. This is the first time, as far as Sinclair is aware, where nerve damage was studied in old rather than young animals. In the case of glaucoma and most diseases, aging is considered largely irrelevant, when of course we know glaucoma is a disease of aging.
A variety of aging clocks, including some the research team built themselves, have been deployed for studies because they are considered the most accurate predictor of biological age and future health, says Sinclair. As embryos, cells lay down different patterns of methylation to ensure they remember their purpose over the next 80 to 100 years.
For unknown reasons, methyl groups get predictably added and subtracted from DNA bases across cell and tissue types and even species, Sinclair says. In 2013, UCLAs Steve Horvath (another Life Biosciences cofounder) showed that machine learning could be used to pick out the hot spots and predict individual lifespan depending on how far above or below the DNA methylation line they sit (Genome Biology, DOI: 10.1186/gb-2013-14-10-r115).
A multitude of aging clocks have since been developed. Eventually, we will need some standardization in the field, but there is nothing super-mysterious about aging clocks, says Sinclair. One of my grad students could probably get you one by the end of the day.
Booming Field
Aging research is a rapidly accelerating field and epigenetic reprogramming is poised to become a particularly active area of inquiry. In terms of numbers, there are still only a dozen or so labs intensely working on this, but there are probably a hundred others I am aware of who are getting into it, says Sinclair.
Life Biosciences began with four labs, but new ones are now joining on an almost weekly basis, he adds. Collaborators have expanded work to the ear and other areas of the body beyond the eye, he adds.
Were also reducing the cost of the DNA clock test by orders of magnitude so [biological age prediction] can be done on millions of people, he continues. In the future, aging clocks are expected to be a routine test in physicians arsenal to guide patient care as well as to monitor response to cancer treatment.
Harvard University has already licensed two patents related to the technology used by the aging researchers to Life Biosciences, Sinclair says. The company has built a scientific team with a group of world-class advisors who developed gene therapy for the eye, which will be tested first for the treatment of glaucoma.
The role of chaperone-mediated autophagy in aging and age-related diseases is another promising area of research being pursued by Life Biosciences Ana Maria Cuervo, M.D, Ph.D., professor, and co-director of the Institute of Aging Studies at the Albert Einstein College of Medicine. Cuervo recently reported at a meeting that fasting-induced autophagy, the cells natural mechanism for removes unnecessary or dysfunctional components, can greatly extend the lifespan of mice. She believes the triggering of this process might one day help treat diseases such as macular degeneration and Alzheimers.
The specialty of Manuel Serrano, Ph.D., the fourth company cofounder, is cellular senescence and reprogramming and how they relate to degenerative diseases of the lung, kidney, and heart. He isan internationally recognized scientist who has made significant contributions to cancer and aging research and works in the Institute for Research Biomedicine in Barcelona.
The rest is here:
Reversing The Aging Clock With Epigenetic Reprogramming - Bio-IT World
- Skin science: Latest stories on cosmetics science and formulation - CosmeticsDesign-Asia.com - November 15th, 2024
- The Firsthand Results Of A Nanofat Treatment Using Stem Cells And PRP - Forbes - November 15th, 2024
- Boundary-Pushing Skin Care Company Exoceuticals Garners Beauty Innovation Award For 'Beauty Innovation Technology Of The Year - The Manila Times - November 15th, 2024
- New skin research could help slow signs of ageing - BBC.com - October 21st, 2024
- Human skin map gives 'recipe' to build skin and could help prevent scarring - Medical Xpress - October 21st, 2024
- A new cell therapy company takes its vision from four founders, and its skin from George Church - STAT - September 23rd, 2024
- Women 60+ love this hydrating stem cell-infused moisturizer that's $15 right now - Yahoo Life - September 23rd, 2024
- NKGen Biotech Publishes Phase 1 Interim Analysis Results of SNK02 Allogeneic NK Cell Therapy in Advanced Solid Tumors at the 2024 American Society of... - May 25th, 2024
- FibroGen Announces Presentation of Positive Interim Data from the Phase 1b Study of FG-3246 (FOR46) in Combination with Enzalutamide in Patients with... - May 25th, 2024
- Cogent Biosciences Appoints Cole Pinnow as Chief Commercial Officer - May 25th, 2024
- G1 Therapeutics Announces Upcoming Presentation at the 2024 American Society of Clinical Oncology (ASCO) Meeting - May 25th, 2024
- Updated Phase 1 Clinical Data for SYS-6002 (CRB-701) to be presented at 2024 ASCO Annual Meeting - May 25th, 2024
- Affimed Announces Positive Early Efficacy and Progression Free Survival Results of AFM24-102 Study in EGFR Wild-Type Non-Small Cell Lung Cancer at the... - May 25th, 2024
- SpringWorks Therapeutics Announces Data to be Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting - May 25th, 2024
- Sensei Biotherapeutics Presents Promising Clinical Data from Phase 1 Dose Escalation Study of SNS-101 - May 25th, 2024
- Elicio Therapeutics Announces Preliminary Data from the Ongoing AMPLIFY-7P Phase 1a Study of ELI-002 7P in Patients with mKRAS-driven Solid Tumors at... - May 25th, 2024
- Kronos Bio to Present Clinical Update on Phase 1/2 Trial of KB-0742 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting - May 25th, 2024
- Coherus Presents Preliminary Results from Phase I Dose Escalation Study of its Anti-chemokine receptor 8 (CCR8) Antibody, CHS-114, at the 2024... - May 25th, 2024
- 3Daughters to Participate in Women’s Health Panel During the 2024 BIO International Convention in San Diego, CA, June 3-6 - May 25th, 2024
- HUTCHMED Highlights Presentations at the 2024 ASCO Annual Meeting - May 25th, 2024
- Myriad Genetics Showcases New Research and Product Innovations Advancing Cancer Care at 2024 ASCO® Annual Meeting - May 25th, 2024
- Lift BioSciences Announces Abstract Publications at the American Society of Clinical Oncology (ASCO) Annual Meeting - May 25th, 2024
- Nicox: 2024 Ordinary Shareholder Meeting to be held on June 28th, 2024 - May 25th, 2024
- Adlai Nortye Ltd. to Present Encouraging Data of the Combination of AN0025 and Definitive Chemoradiotherapy (dCRT) at ASCO 2024 - May 25th, 2024
- Vitamin A could have a key role in both stem cell biology and wound healing: Study - Medical Dialogues - March 10th, 2024
- Cyclerion Strengthens Board of Directors with Experienced Company Builder and Cutting-edge Innovator - December 4th, 2023
- Aptose Appoints Fletcher Payne Chief Business Officer, Expanding his Executive Role - December 4th, 2023
- Opthea to Present at the FLORetina 2023 Congress - December 4th, 2023
- HUTCHMED Highlights Clinical Data to be Presented at 2023 ESMO Asia and ESMO Immuno-Oncology Congresses - December 4th, 2023
- AC Immune Strengthens Management, Appoints Madiha Derouazi as CSO and Christopher Roberts as CFO - December 4th, 2023
- Publication of a transparency notification received from Tolefi SA (Article 14 §1 of the Law of 2 May 2007) - December 4th, 2023
- Annovis Bio Appoints Andrew Walsh as Vice President Finance - December 4th, 2023
- Foghorn Therapeutics Announces Clinical Data from Phase 1 Study of FHD-286, a Novel BRG1/BRM Inhibitor, in Patients with Advanced Hematologic... - December 4th, 2023
- Akari Therapeutics Appoints Experienced Life Sciences Entrepreneur Samir R. Patel, M.D. to Board of Directors - December 4th, 2023
- Ovid Therapeutics to Present Five Abstracts Supporting its Epilepsy Programs at the 77th American Epilepsy Society Annual Meeting (2023) - December 4th, 2023
- Spectral Medical Announces CFO Departure - December 4th, 2023
- Are STEM CELL EXOSOMES the secret to a 'snatched' jawline? Discover the products that influencers are claiming - Daily Mail - November 18th, 2023
- Defence Mechanisms: Four ways your body is protecting you every time you fall sick - indulgexpress - May 16th, 2023
- Treat Yourself to a Spa Day With a $100 Deal on $600 Worth of Products From Elemis, 111SKIN, Nest & More - E! NEWS - May 16th, 2023
- INTERNATIONAL STEM CELL CORP MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com - April 5th, 2023
- Skin Regeneration: The Science and How to Boost It - Healthline - March 9th, 2023
- Treat Yourself to a Spa Day With a $100 Deal on $600 Worth of Products From Elemis, U Beauty, Nest & More - E! NEWS - March 1st, 2023
- 7-year-old vows to find a cure for brother in need of bone marrow transplant - WJLA - February 21st, 2023
- World's most radioactive man 'cried blood' as his skin melted in 83-day nightmare - Times Now - February 4th, 2023
- How old are you, really? The answer is written on your face. - National Geographic UK - February 4th, 2023
- Skin: Layers, Structure and Function - Cleveland Clinic - January 27th, 2023
- Human skin | Definition, Layers, Types, & Facts | Britannica - January 27th, 2023
- Skin Disorders: Pictures, Causes, Symptoms, and Treatment - Healthline - January 27th, 2023
- Skin care: 5 tips for healthy skin - Mayo Clinic - January 27th, 2023
- Skin Care and Aging | National Institute on Aging - January 27th, 2023
- Wrinkles - Symptoms and causes - Mayo Clinic - January 27th, 2023
- Dry skin - Symptoms and causes - Mayo Clinic - January 27th, 2023
- Stem cells: a brief history and outlook - Science in the News - January 3rd, 2023
- Still Drinking Green Tea? Doctor Reveals A Healthier Drink With Proven Benefits For Diabetes, Aging, Oxidative Stress, And Cancer - Revyuh - January 3rd, 2023
- RUDN Physician And Russian Scientists Investigate Long-term Effects Of Treating Diabetic Ulcers With Stem Cells - India Education Diary - December 25th, 2022
- The Use of Stem Cells in Burn Wound Healing: A Review - Hindawi - December 1st, 2022
- FACTORFIVE Skincare The Power of Stem Cells for Skin - December 1st, 2022
- Embryonic Stem Cells - The Definitive Guide | Biology Dictionary - December 1st, 2022
- From pro soccer hopeful to hip hop artist with illness and addiction along the way, Tymaz Bagbani releases debut album - Toronto Star - December 1st, 2022
- Stem Cells | The ALS Association - November 22nd, 2022
- What is a stem cell? YourGenome - October 29th, 2022
- Skin Cell - The Definitive Guide | Biology Dictionary - October 29th, 2022
- Explora Journeys Plans Extensive Fitness And Well-Being Initiatives At Sea, Right On Trend - Forbes - October 29th, 2022
- Ahead of the holiday shopping season, Amazon kicks off second annual Holiday Beauty Haul on Oct. 24 - KXAN.com - October 21st, 2022
- Human skin color - Wikipedia - October 13th, 2022
- Mesenchymal Stem Cells | Properties, Process, Functions, & Therapies - October 13th, 2022
- Skin Grafting, Cryopreservation, and Diseases: A Review Article - Cureus - October 13th, 2022
- Anti-ageing cosmetics: Can they turn back the hands of the clock? - The Sunday Guardian Live - The Sunday Guardian - October 13th, 2022
- Brennand named Elizabeth Mears and House Jameson Professor of Psychiatry - Yale News - October 13th, 2022
- The Switch to Regenerative Medicine - Dermatology Times - October 13th, 2022
- Last Chance to Get The Collagen-Infused Massage Oil That Moisturizes Skin & Diminishes Cellulite For Less Than $20 - msnNOW - October 13th, 2022
- Addison's Disease Explained: Causes, Symptoms, And Treatments - Health Digest - October 13th, 2022
- Stem Cells Therapy for Autism: Does it Work? - October 5th, 2022
- Stem-like CD8 T cells mediate response of adoptive cell ... - PubMed - October 5th, 2022
- 6 Under Eye Products You Need To Have STAT - Grazia India - October 5th, 2022
- CellResearch Corporation (CRC) to present promising new stem cell products for the treatment of chronic diabetic foot ulcers at the world's premier... - September 27th, 2022
- Reprogramming pig cells leads way for new regenerative therapies - National Hog Farmer - September 27th, 2022
- A glimpse into Indian consumers expectations for cosmetic treatments and consumption insights - The Financial Express - September 27th, 2022
- Tajmeel redefines beauty to give its patients the best results - Gulf News - September 27th, 2022
- Here Is Why You Heal Slower As You Age - Health Digest - September 27th, 2022