The Arising · Movement

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 AMERICAN COLLEGE OF CARDIOLOGY Cardiologists Urge Doctors to Prescribe Exercise as Routine Heart Care You may not need 10,000 steps a day to protect your heart. A new statement from the American College of Cardiology says the biggest gains come when inactive people start moving at all. This is an expert scientific statement that synthesizes existing evidence, not a new trial, and it is written mainly as guidance for clinicians. he statement, published online October 15, 2026, in JACC, asks doctors to treat exercise as a foundational part of routine cardiovascular care. It coversT both preventing heart disease and managing it. The writing committee was chaired by Jonathan N. Myers, PhD. Its central message is simple. "Some activity is better than none," Myers said. According to the statement, the greatest benefit comes when people move from inactivity to regular physical activity. More activity, and more intensity where clinically appropriate, is linked to further benefit. THE ARISING · OCTOBER 18, 2026 PAGE 6 What counts as enough? The statement points to growing evidence that meaningful benefits come well below 10,000 steps a day. About 5,000 to 7,000 daily steps is associated with lower cardiovascular and all-cause mortality for many adults. That is an association seen in studies of populations. It does not prove that walking that amount is the cause of the lower risk. This is the weakest part of the argument: the step-count evidence is observational. "Patients do not need to become athletes to improve their cardiovascular health," Myers said. "Small increases in physical activity can produce meaningful benefits, particularly for those who are currently inactive." Strength work gets a place in the plan too. The statement says resistance training should complement aerobic exercise for most adults. Aerobic exercise is walking, cycling or anything that raises your heart rate for a sustained period. Resistance training means lifting weights, using bands or doing bodyweight exercises. The statement recommends doing both. The statement also says exercise should be individualized. A plan should reflect a person's heart condition, functional capacity, symptoms, goals and preferences. A person recovering from a heart event needs a different plan than someone with no symptoms who is trying to stay healthy. On testing, the statement says routine exercise testing is not required before starting exercise for most people who have no symptoms or whose conditions are stable. Testing can still provide useful information for shaping a prescription when it is clinically appropriate. For many people with known heart disease, cardiac rehabilitation remains first-line treatment, the statement says. Access to it should be expanded. Insurance reimbursement is still a barrier for many. Patients with known heart disease who cannot take part in a formal program should still receive an individualized exercise prescription. The statement also says wearable devices and virtual or home-based programs may help people keep exercising over time, especially alongside structured programs. Myers said exercise is one of the most effective therapies for preventing and managing cardiovascular disease, yet it remains underutilized in routine care. The statement calls for more exercise counseling in routine visits, better clinician training and expanded access to rehabilitation. THE ARISING · OCTOBER 18, 2026 PAGE 7 Exercise is not a replacement for medical care. Do not start, stop or change any treatment, including medications or a prescribed rehabilitation plan, without your clinician. The statement is written for clinicians, so questions about how it applies to you belong with your own care team. The statement also calls for more research on long-term adherence, clinical outcomes, diverse populations and scalable ways to deliver exercise programs. Watch for whether those studies follow, and whether insurers move on cardiac rehabilitation coverage. Source: American College of Cardiology (JACC) THE ARISING · OCTOBER 18, 2026 PAGE 8

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 · MARKETS & STRATEGY SUNDAY, OCTOBER 18, 2026 IN THIS EDITION · MARKETS & STRATEGY 1 Major Hospitals Open Longevity Clinics, and STAT Asks Whether They Work 2 PPIC Projects California's 65-Plus Labor Force Will Reach 1.8 Million by 2040 3 FDA Approves Viatris' Ryzumvi Eye Drops for Presbyopia in Adults 4 Wyden Seeks Input on Medicare or Medicaid Universal Home Care Benefit 5 Atrogi's Oral Muscle Drug Linked to 13% Power Gain in Small Study 6 Over 90% of US Nursing Homes Staff Below Acuity-Based Expected Level, LTCCC Says MARKETS & STRATEGY · WEEKLY READ · 2 MIN PIPELINE AND COMPETITIVE POSITIONING · PHARMATIMES Atrogi's Oral Muscle Drug Linked to 13% Power Gain in Small Study A pill that could add muscle while taking off fat would stand apart in a weight-loss field where, by widely reported background not drawn from this source, many drugs tend to cost people lean mass. Atrogi says it now has early human data pointing that way. The study was small, open-label and had no control group, and we could not confirm whether it has been peer-reviewed, so the claim is far from proven. The drug was associated with the gain, which is not the same as causing it. This is an investigational drug: do not start or stop any medication, treatment or supplement without talking to your clinician. his article is based on PharmaTimes' report of the study. The paper itself was not retrieved or reviewed, and nothing here has been checked against it.T According to PharmaTimes' report, Atrogi announced positive human data for ATR- 258. The company describes it as a first-in-class oral GRK2-biased β2-adrenergic modulator, designed to improve muscle function and body composition. PharmaTimes reports that the study ran for 8 weeks in 13 overweight or obese adults. It was investigator-initiated, open-label and single-arm, so there was no placebo group. It tested three ascending dose levels. Professor Morten Hostrup led it. THE ARISING · OCTOBER 18, 2026 PAGE 33 According to the report, the therapy was well tolerated and associated with an approximately 13% mean improvement in lower-extremity muscle power. Mean fat mass fell by 1.1 kg and lean mass rose by 0.8 kg. PharmaTimes says the changes in fat and lean mass were statistically significant. On positioning, the company is pitching a differentiated profile: fat loss alongside more lean mass and better muscle function. Chief Scientific Officer and founder Tore Bengtsson said the data "give us important confidence that our approach is translating." He also said the mechanism warrants investigation in sarcopenia and in rare diseases marked by major muscle loss and weakness. The report says the results build on a 2025 Cell publication. That paper described the GRK2-biased signalling approach and first-in-human safety data from a 69-subject phase 1 trial. PharmaTimes says the new results give first human proof of mechanism and support a phase 2 trial planned for 2027. That proof-of-mechanism framing comes from the company announcement. Hostrup, the principal investigator, also commented, saying the magnitude of the signal in lower-extremity power struck him most. CEO Paul Little called Atrogi "a phase 2-ready biotech." For strategy, the case rests on a gap the company is aiming at: muscle-sparing options in metabolic disease and possible uses in muscle-wasting conditions. Several points are not in the coverage. These include how the drug compares with existing treatments, how regulators would view muscle power as an endpoint, and what a phase 2 trial would cost. Those are open questions, not findings. The caution is plain, and this is where the argument is weakest. With 13 people and no control group, the study cannot separate the drug's effect from other influences. The coverage also gives no data on how long any gains last. The company's own statements make up much of the report. WHAT TO WATCH NEXT The design and endpoints of the phase 2 trial planned for 2027, and whether a placebo-controlled study confirms the muscle power signal. Source: PharmaTimes THE ARISING · OCTOBER 18, 2026 PAGE 34