The Arising · Frontiers

THE ARISING · LONGEVITY & HEALTHSPAN SUNDAY, OCTOBER 18, 2026 IN THIS EDITION · LONGEVITY & HEALTHSPAN 1 ACOG Now Recommends Hormone Therapy for Many Women With Hot Flashes 2 Cardiologists Urge Doctors to Prescribe Exercise as Routine Heart Care 3 Fasting and Autophagy in Humans: Summary Calls Link Unproven 4 Gut Supplements May Modestly Improve Cognition in Adults Over 60, Review Finds 5 Higher Ultra-Processed Food Intake Linked to Silent Brain Damage on MRI 6 Higher VO2 Max Linked to Lower Depression and Anxiety Risk in UK Biobank 7 Bonn Lab Study Shows Blood Cells From Older Donors Lose Epigenetic Age in a Dish 8 Longer Sleep Linked to Kidney Disease Risk in Type 2 Diabetes LONGEVITY & HEALTHSPAN · WEEKLY READ · 3 MIN AGING CELL · 2 SOURCES Bonn Lab Study Shows Blood Cells From Older Donors Lose Epigenetic Age in a Dish Blood cells from very old donors can be converted in a dish into neural stem cells whose DNA-based age reads far younger, but nothing in this work turns back the age of a person. The widely quoted figure that cells from an 80-year-old reached a molecular age under 20 comes from press coverage, not from the study text we have. he study, published in Aging Cell in 2026 by Berg and colleagues at the University of Bonn and partner institutions, is laboratory research on humanT cells. It did not involve animals or patients. The text available to us does not state how many donors were used. It says only that donors ranged from newborns to people aged 101. The team took red blood cell precursors from donor blood. They added two genes, SOX2 and cMYC, using a virus. This pushed the cells to become induced neural stem cells, which can go on to form brain cells. Unlike the more common route, the cells did not first pass through a pluripotent stage, in which a cell can become almost any tissue. THE ARISING · OCTOBER 18, 2026 PAGE 19 To estimate age, the researchers used an epigenetic clock. This is a computer method that reads chemical tags on DNA, called methylation, which change with age. The tags do not alter the genetic code. They affect how often genes are read. According to the study, neural stem cells made from older donors kept only about 13% of the donor's original age at low passages, meaning early rounds of cell growth. At high passages, meaning many rounds of growth, they kept about 5%. By our arithmetic, 13% of 80 years is roughly 10 years. The new finding is about timing. The age reset was not instant. It continued for several weeks, and it continued even when conditions were set to block cell division. Differences in gene activity between young and old donors' cells also faded with more time in conversion. The authors say the established cell lines lacked age- associated cellular hallmarks, much like cells made through the pluripotent route. The cells also took a long time to settle into a true neural stem cell identity. According to the paper, that process went on well after the first cells with a neural stem cell marker, PAX6, appeared. The press release, as carried by AZO Life Sciences, reports that cells from an 80-year- old came out with a molecular age below 20. It quotes Prof. Oliver Brüstle of the University Hospital of Bonn saying the slow pace makes it possible to "investigate which factors and active substances accelerate or slow down the rejuvenation process." The coverage's headline mentions 50 days, while its text says the change could be tracked for over 100 days. The study's abstract says only "several weeks," so the exact timeline is unclear from what we have. FOR YOU What does this mean for readers? Not much yet, and the limits matter. The study's own introduction notes that methylation age is a proxy for biological age. It is not a direct measure of how well cells work. The coverage says the rejuvenation makes cells "actually behave like young cells," but the abstract supports a narrower claim: the cell lines lack age-associated hallmarks. The cells were also not the same cells that were taken from the donors. They were changed into a different cell type, grown in dishes, and treated with viral vectors. Nothing here shows that an aging body, or even an aging organ, can be reset. The study tested no treatment, drug or supplement. THE ARISING · OCTOBER 18, 2026 PAGE 20 The practical value is in research. A slow reset is easier to watch step by step than a fast one. It may help scientists find what drives epigenetic aging and whether it can be sped up or slowed down. Age is the main risk factor for diseases such as Alzheimer's, which is why Brüstle says the model matters for neuroscience. The work was funded by the EU's Horizon 2020 programme, the German Research Foundation and Germany's federal research ministry, according to the coverage. Next, watch for follow-up work that identifies which molecules speed up or slow the reset, and whether any of those findings hold up in living tissue. Sources: Aging cell (2026), AZO Life Sciences (reporting University of Bonn study in Aging Cell) THE ARISING · OCTOBER 18, 2026 PAGE 21

OCTOBER 16, 2026 A claim that a diet or supplement "reversed biological age" may rest on a single test reading, and a new analysis suggests that is often not enough to trust. The study re-examined only three published single-clock results, so it does not show that most such claims fail. It shows that those three did not hold up across a wider panel of clocks. A field becomes more capable when it improves the way it judges its results. Re-examining clock-based claims is part of that work, particularly when small changes are asked to carry large meanings. The work was published in Aging Cell in 2026 by Daniel Borrus, Albert Higgins-Chen and colleagues at Yale. It is a re-analysis of existing data, not a new trial. The team took longitudinal DNA methylation datasets, in which the same people were tested before and after an event or intervention, and ran 12 epigenetic clocks on each. The text available to us does not give participant numbers for the datasets, so we do not report them. These are studies in people, and the results show patterns in test readings. They do not show effects on lifespan. Epigenetic clocks estimate biological age from chemical marks on DNA, read from a blood sample. The clocks differ. Early ones, such as Hannum and Horvath, were trained to predict calendar age. Later ones, such as PhenoAge and GrimAge, were trained to predict mortality risk. The Dunedin measures estimate pace of aging. The team also tested more reliable versions of six clocks, called PC clocks, built to reduce measurement noise. Noise is a real issue. According to the authors' earlier work, re-testing the same person with standard clocks can shift the result by 0.9 to 2.4 years. PC clocks cut that to 0.3 to 0.8 years. A change of a year or two on one test could therefore be chance. The researchers first revisited three published datasets that had reported a significant drop in biological age on one clock. Two were an 8-week diet, exercise and supplement program and a 2-year folic acid and vitamin B12 trial, both reported on the Horvath multi-tissue clock. They calculated 11 more clocks on the same data. None changed significantly in the same direction as the original finding. The study says this raises questions about whether such single-clock results are real or statistical artifacts. Bioengineer.org, which covered the paper, adds that in one dataset ten of the eleven extra clocks trended the opposite way. That detail comes from the coverage. To learn what a trustworthy signal looks like, the team used events known to raise mortality risk: intensive surgery, radiation and chemotherapy, and SARS-CoV-2 infection. In all three datasets, at least 4 of the 12 clocks rose significantly. PCPhenoAge, PCGrimAge and DunedinPACE rose in all three. The older chronological clocks (Hannum, Horvath multi-tissue and Horvath skin-and-blood) showed no significant increase in any. The skin-and-blood clock showed a significant decrease after radiotherapy and chemotherapy. From this, the authors derived three criteria for more confidence. Per Bioengineer.org's summary, the reliable PC clocks should respond, the mortality-trained or pace-of-aging clocks should respond, and multiple clocks should move in the same direction. The authors also suggest averaging all 12 clocks per person as a quick filter for whether the clocks agree. They stress it is not a new biomarker. Some interventions did pass. The study identified three datasets that met the criteria. According to the Bioengineer.org coverage, these included a two-year Mediterranean diet trial with a standard arm and a green Mediterranean arm, and a three-week alcohol abstinence program in chronic drinkers. The coverage reports significant decreases in at least five clocks, and the 12-clock average fell significantly in every case. In plain terms, diet and cutting alcohol produced shifts that showed up across several clocks, which is the pattern the authors consider convincing. This does not mean anyone should change their diet, start or stop a supplement, or stop drinking on their own. Abrupt alcohol cessation in heavy drinkers can be medically dangerous, so talk with your clinician first. There is a further caution. Blood tests reflect the mix of immune cells as well as cell aging. The coverage reports that after adjusting for this, surgery and chemotherapy effects shrank by about three-quarters, while the COVID-19 effect barely changed and the Mediterranean diet arms kept most of theirs. The authors say researchers should report such adjustments. For anyone weighing a biological-age test or an age-reversal advertisement, the study does not offer consumer guidance, but its logic suggests some questions of our own. Does the result come from one clock or many? Do reliable and mortality-based clocks agree? Was the change larger than the known retest noise? These are our extrapolation, not the authors' advice. A clock change also does not by itself mean added years of life. The main limitation is that the criteria were derived from a handful of datasets, and the study is a re-analysis rather than a new trial. Watch next for trials that report several clocks, including reliable ones, and that publish the results that did not reach significance. Agreement across reliable measures would make a claim more credible. Connecting those measures to outcomes would make it more useful. Sources: Aging cell (2026), Bioengineer.org (Yale University / Aging Cell) Aging cell (2026): https://doi.org/10.1111/acel.70756 Bioengineer.org (Yale University / Aging Cell): https://bioengineer.org/epigenetic-clocks-need-a-reality-check-before-anti-aging-claims/ ---

OCTOBER 11, 2026 A gene therapy designed to turn back the clock on aging cells has now been given to people, and in the first three patients it was well tolerated. For a field built around the possibility of restoring function, the first human observations carry particular weight. They also demand proportion: three participants and eight weeks can open a question, but cannot settle it. Life Biosciences announced the interim results on October 8, 2026, from its Phase 1 trial of a therapy called ER-100. The three participants all have open-angle glaucoma, a chronic disease in which the optic nerve is damaged. It is a leading cause of blindness in older adults. According to the company, vision lost to glaucoma is often considered irreversible, because the nerve cells involved, called retinal ganglion cells, do not naturally regenerate. ER-100 takes an unusual approach. It delivers three genes known as OCT4, SOX2 and KLF4, together called OSK. According to the company, these are used to reset the patterns of gene activity in a cell and return it to a more youthful, functional state. The company calls this epigenetic restoration. In plain terms, the idea is to change which genes are switched on, rather than to fix a single faulty gene. Each participant received one injection into the eye. They also took the antibiotic doxycycline by mouth every day for 56 days. The doxycycline acts as a switch that turns the OSK genes on. A course of oral steroid, tapered down over time, was given to limit inflammation from the immune response to the virus used to deliver the genes. On safety, the company reports no dose-limiting toxicities, no serious adverse events and no adverse events of special interest through Day 56. All side effects that were reported were linked to the injection procedure, the steroid or conditions the patients already had, according to Life Bio. That attribution comes from the company, not an independent review. The trial's Data Safety Monitoring Board recommended moving to a higher dose, about three times the first one. The vision results are the part that draws attention. Two of the three participants improved on the Humphrey visual field test, a standard exam that measures how well a person detects light across many points in their field of vision. In each of those two, at least 28% of test points improved by more than 4 decibels. The company called these observations preliminary and encouraging. Here is why caution matters, and this is where the argument is weakest. Three patients is a very small group. The trial is open-label, meaning everyone knew they were receiving the treatment. The company's materials do not describe a comparison group, so we cannot tell whether the gains exceed what would be expected without treatment. Follow-up so far is only 56 days. Visual field tests can vary from one session to the next, so it is not possible to say whether the gains came from the therapy. The company itself notes that this phase of the study is designed to evaluate safety and tolerability. ER-100 is investigational, and the company's materials describe it as being evaluated in the trial, registered as NCT07290244. Please do not start, stop or change any glaucoma treatment, or any medication, including antibiotics such as doxycycline or steroids, on the basis of this report; talk to your own clinician first. Phase 1 trials are the first step, and as a general rule, later and larger studies would be needed to show that a therapy works and remains safe over longer periods. That means any approved treatment, if one ever emerges, is likely years away, though that is our judgment rather than something the company has stated. Still, the result matters for a broader reason. It is early human evidence that a controlled version of this cell-reprogramming approach can be given to patients without obvious serious harm at the starting dose. The company says it hopes the method can eventually address other age-related diseases, but that remains unproven. WHAT TO WATCH NEXT Results from the higher-dose group, longer follow-up in the first three patients, and whether the trial's planned inclusion of patients with another optic nerve condition, NAION, produces data of its own. The next advance will be more follow-up, more participants, and a clearer account of what changed. That is how an extraordinary possibility becomes something medicine can judge. Source: Life Biosciences (press release; also reported by STAT) Life Biosciences (press release; also reported by STAT): https://www.lifebiosciences.com/life-biosciences-announces-first-in-human-data-from-ongoing-phase-1-trial-evaluating-er-100-in-optic-neuropathies/ ---