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November was a rollercoaster ride in the rejuvenation world, with plenty of ups and downs along with twists and turns. Progress in the field continues apace, as CRISPR is in Phase 1 human clinical trials and researchers have reported success with removing Oct4 from the OSKM cocktail – but there is some less fortunate news as well.

LEAF News

Team and activities

João Pedro de Magalhães at Ending Age-Related Diseases 2019: We released the final EARD video early in November, and in it, Dr. de Magalhães had a lot to say about genetics and drug discovery.

Natasha Vita-More Joins the LEAF SAB: The LEAF scientific advisory board has a new member: Dr. Vita-More, an ethicist and proponent of human augmentation.

Keith Comito Appears on the Geekdom 101 Podcast: The team of Geekdom 101 gave LEAF President Keith Comito the opportunity to talk about aging and the work that our organization does to assist the development of interventions against it.

LifeXtenShow

Life Extension in Fiction: A new member joins the X10 crew, and she quizzes the guys on various portrayals of life extension in familiar, and unfamiliar, fictional media.

Ending Age-Related Diseases 2019: This overview of EARD2019 features poignant statements from many of the researchers who attended our conference this year.

Rejuvenation Roundup Podcast

Ryan O’Shea of Future Grind hosts this month’s podcast, showcasing the events and research discussed here.

Lifespan.io Interviews

Are Senolytics Potentially Damaging for Longevity?: In this discussion about telomerase and senescent cells, Dr. Michael Fossel makes some thought-provoking comments about the potential value of senolytics as a therapy.

Research Roundup

Adjusting Gut Bacteria to Combat Cognitive Decline: A recent paper explores modifying the gut microbiome to increase production of butyrate and brain-derived neurotrophic factor (BDNF) in order to aid the brain and fight against age-related cognitive diseases.

One Combination Gene Therapy Treats Multiple Age-Related Diseases: A team led by Dr. George Church has formulated a gene therapy that has successfully treated a mouse model of age-related diseases, including obesity and diabetes. We discussed this paper in this month’s Journal Club, which all our Lifespan Heroes are welcome to join.

Excluding Oct4 from OSKM Yields Positive Results: In what is certain to be a major surprise for the field of iPSCs, researchers have recently discovered that Oct4 may not be necessary for an epigenetic reset – and have a possible explanation for why it was considered necessary.

New Potential Treatment for Atherosclerosis Identified: Researchers have identified a protein, Tribbles 1, that is responsible for macrophages turning into the deadly foam cells that cause atherosclerosis; the next step is to develop a treatment that targets this protein.

Human Safety Trial of NMN Concludes: A group of researchers in Japan have conducted an independent early trial of NMN and determined it to be safe for human use.

CRISPR Human Trial Results Look Promising for Safety: Use of CRISPR on human beings has begun, and the gene editing tool has, in the preliminary portion of a Phase 1 trial, shown itself to be safe in creating a therapy against cancer.

7-ketocholesterol Drives Atherosclerosis: SENS’ new spin-off company, Underdog Pharma, is targeting this deadly, oxidized form of cholesterol, which macrophages fail to digest in the process of becoming dangerous foam cells.

Being Physically Fit Reduces the Risk of Dementia: Yet more evidence shows that exercise reduces the incidence of age-related diseases – including cognitive decline.

Gut Microbes Support Neurogenesis and Longevity Hormone Production: Another look at the gut-brain axis, this time with a view towards neurogenesis, the production of new neurons in the brain.

Caloric Restriction Restores Myelinating Cell Populations: Caloric restriction, as well as the CR mimetic metformin, have shown to be effective in restoring populations of the cells that produce myelin, which is destroyed in autoimmune disorders such as multiple sclerosis.

Purifying Stem Cell Therapies with Suicide Genes: Stem cell therapies are often contaminated with pluripotent stem cells that would be dangerous if injected; a new gene therapy can can these dangerous cells to kill themselves instead.

Berberine Downregulates p16 and Delays Senescence: While the mechanisms are not yet fully understood, injected berberine has been shown to have beneficial effects on cancer cells, delay senescence, and extend lifespan in mice.

mTOR Drives Cerebrovascular, Synaptic, and Cognitive Dysfunction: In this rat study, mTOR has been shown to be a primary cause of multiple cognitive issues, and its attenuation with rapamycin has been shown to have beneficial effects.

The Plasma Metabolome as a Predictor of Biological Aging in Humans: Blood levels of certain metabolites can be used as a biological clock, and the way these metabolites are formed can serve as a basis to spur additional insights into aging.

Nicotinamide Riboside Does Not Affect Mitochondria in Obese or Insulin-Resistant Men: This disappointing but informative study has shown that administration of NR is ineffective in assisting mitochondria in the skeletal muscle of this older cohort.

Slower DNA Damage in Leukocytes Correlates with Slower Aging Between Species: This study from the Maria Blasco lab shows the effects of genomic instability between different species, with an inverse correlation between damage and longevity.

Microbiome Deficits Associated with Chronological Age: This study provides evidence for a greater diversity in bacteria in aged individuals and a failure of the aged microbiome to produce tryptophan, an amino acid responsible for the production of NAD+.

Senescent Cells Linked to Rheumatoid Arthritis: Senescent fibroblasts have been shown to accumulate in the synovial tissues of people suffering from this crippling condition, and this study demonstrates a link between the senescence-associated secretory phenotype (SASP) and the harmful effects of inflammaging.

Rotating Magnetic Field Delays Aging in Cells and C. Elegans: This particularly unusual study was only conducted on human cells and nematodes, not mice or human beings, but it provides insight into the effects of a rotating magnetic field on calcium ions and the production of ATP, which, in turn, affect longevity.

News Nuggets

A New Healthcare Framework for Aging Populations: Dr. Stuart Calimport, Dr. João Pedro de Magalhães, and scientists and doctors around the world offer a potential framework for recategorizing age-related ailments.

Dr. Greg Fahy Appears on The Damage Report: In this interview, Dr. Fahy discussed his company, Intervene Immune, and its clinical trial that showed the effectiveness of thymus regeneration on immune health.

Underdog Pharma Launches and Sets Its Sights on Atherosclerosis: SENS Research Foundation has spun off a new company with the aim of combating atherosclerosis, the number one killer worldwide.

Disappointing Results for ResTORbio Human Trial: ResTORbio’s drug, the rapalog RTB101, did not meet expectations in a Phase 3 trial for treatment of respiratory infections.

Irresponsible Marketing Surrounds Telomerase Human Trials in South America: Some of Libella Gene Therapeutics’ statements regarding its $1 million per-patient trial in Colombia are extremely speculative at best.

Positive Results of a Human Trial for Skin Aging: Rapamycin, administered through the skin with DMSO, was shown to thicken skin and increase collagen, partially reversing the effects of skin aging.

A Thorough Overview of Aging Clocks: Drs. Vadim Gladyshev and Steve Horvath, among other researchers, offer an overview of the epigenetic clocks that can be used to determine biological age.

Targeting Senescent Cells in Translational Medicine: This exhaustive overview of senescence, senescent cells, and the SASP shows the ways in which they can be targeted in the clinical setting to fight against multiple diseases, including cancer.

Coming up in December

Giving Tuesday: Tomorrow, December 3, Facebook is hosting its annual charitable event. For every donation made on Giving Tuesday, Facebook will be matching all donations of up to $7 million, making it the perfect day to show you care!

Thank you for reading and sharing our articles; your continued support, in whatever form it may come, is what keeps us going. As usual, special thanks go to the Lifespan Heroes, who allow our organization to stay in business and carry out its activities through their generous donations. Conferences, webinars, YouTube shows, news reports—none of these would be possible without your help. If you’d like to be a Lifespan Hero, visit lifespan.io/hero to make your monthly pledge.

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