The Arising · The Evidence

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 · 2 MIN JOURNAL OF AFFECTIVE DISORDERS · 2 SOURCES Higher VO2 Max Linked to Lower Depression and Anxiety Risk in UK Biobank Adults with higher aerobic fitness were less likely to be diagnosed with depression or anxiety over the following 12 years, according to a large study in the Journal of Affective Disorders. his is an observational study in people. It followed 46,062 UK Biobank participants who had no depression or anxiety at the start. ObservationalT work can show that two things go together. It cannot show that one causes the other. Fitness was measured as VO2 max, the most oxygen a body can use during hard exercise. It is a standard marker of heart and lung fitness. Here it was estimated from a standardized submaximal exercise test, meaning participants were not pushed to their limit. The researchers, led by Liu Y, tracked new cases of depression and anxiety through linked health records coded with ICD-10, a standard system for recording diagnoses. THE ARISING · OCTOBER 18, 2026 PAGE 16 Over a median follow-up of 12.6 years, there were 2,190 cases of depression and 2,483 cases of anxiety. Compared with the least fit quarter of participants, the fittest quarter had a 24% lower risk of depression (hazard ratio 0.76, 95% confidence interval 0.64–0.91). Their anxiety risk was 17% lower (hazard ratio 0.83, 95% confidence interval 0.71–0.98). These results account for sociodemographic, lifestyle and clinical factors. The pattern also held across the fitness range. For each 1-standard-deviation increase in VO2 max, depression risk was 10% lower (0.90, 0.84–0.96). Anxiety risk was 6% lower (0.94, 0.88–1.00), a result right at the edge of statistical significance. The authors report a straight-line relationship for depression. For anxiety the relationship was nonlinear, so the benefit did not rise in a steady line. The study also reports that associations were stronger among people with a lower biological age. The abstract does not say how biological age was calculated, so that finding is hard to interpret here. The team also looked at blood proteins in a subset of 3,245 participants. They found seven plasma proteins that differed with fitness. Leptin and FABP4 were lower, and SPINT3 and INSL3 were higher. Several of these proteins were independently linked to mental health outcomes. The authors say this points to metabolic and neuroprotective pathways as possible explanations. That is a hypothesis, not a demonstrated mechanism. FOR YOU What does this mean for personal health? Aerobic fitness is already tied to heart health. This study adds that it may also go with a lower chance of common mental health diagnoses. But fitter people may differ from less fit people in ways that statistics cannot fully remove. Early, undiagnosed low mood could also make exercise harder. The abstract does not say how the authors handled that. And because outcomes came from health records, people with symptoms who never sought care would not be counted. The findings sit alongside another recent Arising report, on a separate UK Biobank study linking more REM sleep to lower risk of 83 diseases. Both are observational and both point to modifiable habits. Neither shows that changing the habit changes the outcome. THE ARISING · OCTOBER 18, 2026 PAGE 17 To watch next: randomized trials that assign people to supervised aerobic training and track depression and anxiety diagnoses over time, which would test whether fitness itself makes the difference. Sources: Journal of affective disorders (2026), Medscape (reporting on Journal of Affective Disorders) THE ARISING · OCTOBER 18, 2026 PAGE 18

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

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 JOURNAL OF THE ENDOCRINE SOCIETY · 2 SOURCES Longer Sleep Linked to Kidney Disease Risk in Type 2 Diabetes Sleeping more is usually treated as a good sign. A new study of people with type 2 diabetes suggests that, for kidney health, longer sleep may be a signal worth noticing. he research is a prospective cohort study, a type of observational study in people. It followed 678 Japanese outpatients with type 2 diabetes for anT average of 6.0 years (give or take 2.7 years). It was published in 2026 in the Journal of the Endocrine Society. Observational studies can find links. They cannot show that one thing causes another. The researchers looked at diabetic nephropathy, also called diabetic kidney disease. This is kidney damage caused by long-term diabetes. They counted either new cases or worsening of existing disease as a single combined outcome. During follow-up, 215 of the 678 participants reached that outcome. The team recorded lifestyle habits at the start, and again at year 2 and/or year 5. They averaged each person's measurements up to the point of the outcome or the end of follow-up. Of all the lifestyle factors they examined, average sleep duration was the only one linked to the outcome, according to the study's abstract. THE ARISING · OCTOBER 18, 2026 PAGE 22 The direction mattered. The authors conclude that longer sleep, but not shorter sleep, was associated with a higher risk. The trend held after adjusting for key lifestyle and diabetes-related factors. The link was stronger in older participants and in those who already had microalbuminuria (small amounts of protein in the urine, an early sign of kidney damage) or reduced kidney function. Only the abstract was available to us. It does not give the sleep-hour categories or the size of the risk, so we cannot report them. The authors do not claim long sleep harms the kidneys. In a statement released by the Endocrine Society, study author Tomoya Mita of Juntendo University in Tokyo said longer sleep "may be a readily observable marker of underlying health vulnerability." He also said people should not read the findings as advice to sleep less, because "we cannot establish a causal relationship." The Endocrine Society release also states that diabetic kidney disease affects about 30% to 40% of people with diabetes. FOR YOU What does this mean for personal health? The study did not test sudden changes in sleep. It looked at average sleep over years. Mita said longer sleep may be a useful clue to identify people with diabetes who may need closer attention to their kidney health. Beyond that, any advice here is our editorial suggestion, not a finding of the study: if someone notices a clear, lasting increase in how long they sleep, it may be worth mentioning to a clinician. It may be most relevant to older adults with diabetes and to people whose kidney tests already show early changes. Readers should not change their sleep habits or diabetes care without talking to their clinician. There are limits. All participants were Japanese outpatients with type 2 diabetes, so the results may not apply to other groups. The abstract does not say whether other health conditions could explain the pattern. The weakest point of the argument is that we cannot tell from the abstract what sleep lengths counted as long, or how large the risk was. This differs from the REM sleep study we covered on October 6, which tracked sleep stages and disease risk in nearly 96,000 UK adults. That was a different study with a different design. This one adds that sleep length alone may carry information in a specific group, though both are observational. THE ARISING · OCTOBER 18, 2026 PAGE 23 Next, watch for studies that measure sleep objectively and track changes over time. They could show whether longer sleep helps flag kidney risk in routine diabetes care. Sources: Journal of the Endocrine Society (2026), Endocrine Society / Journal of the Endocrine Society (via Newswise) THE ARISING · OCTOBER 18, 2026 PAGE 24