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Current Research in Longevity and Healthy Aging

Naples Center for Functional Medicine

Current Research in Longevity and Healthy Aging

This page summarizes published research for educational purposes. It is not a list of NCFM treatments or offerings, and it makes no claim that any NCFM therapy slows or reverses aging. Many findings come from animal, small or observational studies, and results may not apply to you. Talk with a physician before acting on any research.

Current Research in Longevity and Healthy Aging. Questions? Call (239) 649-7400 and our team will help.

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Overview

Evidence labels: Human RCT = randomized controlled trial in people (small or pilot trials are marked); Observational = shows an association, not cause and effect; Animal = studies in animals, may not apply to people; Early = small, uncontrolled, pilot or single-case; Review = summary of other studies; Protocol = trial design, no results yet.

Semaglutide is FDA-approved for type 2 diabetes, chronic weight management, and reducing cardiovascular risk in certain adults; rapamycin (sirolimus) is FDA-approved for preventing organ-transplant rejection and certain rare conditions. Neither is FDA-approved to slow aging; such use is off-label.
Other drugs named on this page: metformin is FDA-approved to improve blood-sugar control in type 2 diabetes; dasatinib is FDA-approved for certain leukemias; RTB101 is investigational and not FDA-approved. None is FDA-approved to slow aging. [Label check 2026-10-29 via openFDA/DailyMed: semaglutide (type 2 diabetes; CV-risk reduction; chronic weight management), sirolimus (kidney-transplant rejection prophylaxis; lymphangioleiomyomatosis), metformin (type 2 diabetes), dasatinib (Ph+ CML/ALL)]

Biological aging clocks

  • Observational / biomarker development — Belsky DW et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. Elife, 2022. Introduced DunedinPACE, a blood DNA-methylation measure of how fast a person appears to be aging. PubMed 35029144
  • Review / consensus — Moqri M et al. Biomarkers of aging for the identification and evaluation of longevity interventions. Cell, 2023. Expert consensus on how aging biomarkers might be validated before being used to judge longevity interventions. PubMed 37657418
  • Observational — Cao H et al. MRI-based multi-organ clocks for healthy aging and disease assessment. Nat Med, 2026. Built MRI-based “organ age” clocks and linked faster organ aging with disease in large cohorts. PubMed 41102562

Senolytics

  • Early (phase 1, open-label, 5 people) — Gonzales MM et al. Senolytic therapy in mild Alzheimer’s disease: a phase 1 feasibility trial. Nat Med, 2023. Small, early safety and feasibility trial of dasatinib plus quercetin in mild Alzheimer’s disease; not designed to show benefit. PubMed 37679434
  • Animal — Ruggiero AD et al. Long-term dasatinib plus quercetin effects on aging outcomes and inflammation in nonhuman primates: implications for senolytic clinical trial design. Geroscience, 2023. Long-term dasatinib plus quercetin in aging monkeys, looking at inflammation and aging markers. PubMed 37261678
  • Protocol — Millar CL et al. Rationale and Design of STAMINA: Senolytics To Alleviate Mobility Issues and Neurological Impairments in Aging, A Geroscience Feasibility Study. Transl Med Aging, 2023. Design of an ongoing trial testing senolytics for mobility and cognition in older adults; no results yet. PubMed 40248131

Rapamycin and mTOR

  • Human RCT (small) — Moel M et al. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging (Albany NY), 2025. One-year trial of intermittent rapamycin in healthy adults, mainly safety; some benefits (lean mass, pain) appeared only in women at one dose, and overall healthspan findings were mixed. PubMed 40188830
  • Human RCT — Mannick JB et al. Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials. Lancet Healthy Longev, 2021. Trials of RTB101, an investigational mTOR inhibitor, in adults 65 and older; it was well tolerated and boosted antiviral immune genes, but in the phase 3 trial it did not reduce symptomatic respiratory illness, the primary outcome. PubMed 33977284
  • Observational (self-report) — Kaeberlein TL et al. Evaluation of off-label rapamycin use to promote healthspan in 333 adults. Geroscience, 2023. Survey of adults using rapamycin off-label; self-reported, without a control group. PubMed 37191826

Metformin (TAME)

  • Observational — Shadyab AH et al. Comparative Effectiveness of Metformin Versus Sulfonylureas on Exceptional Longevity in Women With Type 2 Diabetes: Target Trial Emulation. J Gerontol A Biol Sci Med Sci, 2025. In women with type 2 diabetes, metformin users were compared with sulfonylurea users for reaching age 90; association only. PubMed 40388602
  • Review — Manneh J et al. Metformin at the convergence of aging and longevity. Aging (Albany NY), 2026. Review of how metformin might act on aging pathways and the status of trials such as TAME, which is not yet reported. PubMed 42579881

NAD+ precursors

Some clinics, including NCFM, offer services related to this topic. The research below is not evidence that any NCFM service will slow aging or produce these results for you.

  • Review — Freeberg KA et al. Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions. J Gerontol A Biol Sci Med Sci, 2023. Review of human NAD+-booster studies: raises NAD+ levels, but clinical benefits are not yet established. PubMed 37068054
  • Human RCT (small, short) — Yi L et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience, 2023. 60-day trial in 80 healthy middle-aged adults; NMN raised blood NAD levels and appeared well tolerated; other outcomes were secondary. PubMed 36482258
  • Human RCT (pilot) — Martens CR et al. A phase-II randomized controlled pilot study of nicotinamide riboside supplementation in older adults with amnestic mild cognitive impairment. Alzheimers Dement, 2026. Pilot trial in 42 older adults: nicotinamide riboside doubled blood NAD+ but did not improve cognition, the main outcome. PubMed 42478598

GLP-1 medicines and aging

Some clinics, including NCFM, offer services related to this topic. The research below is not evidence that any NCFM service will slow aging or produce these results for you.

  • Human RCT — Lincoff AM et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med, 2023. SELECT trial: semaglutide reduced major cardiovascular events in adults with obesity and heart disease but no diabetes. PubMed 37952131
  • Human RCT (post hoc analysis) — Ostrominski JW et al. Efficacy and Safety of Semaglutide According to Frailty Status: A Post Hoc Analysis of the SELECT Randomized Clinical Trial. JAMA Cardiol, 2026. Secondary analysis of SELECT looking at results by frailty status. PubMed 42747817
  • Human RCT — Cummings JL et al. Efficacy and safety of oral semaglutide in early-stage symptomatic Alzheimer’s disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials. Lancet, 2026. Phase 3 trials: oral semaglutide did not slow progression of early Alzheimer’s disease. PubMed 41865758

Exercise and VO2max

  • Observational (umbrella review) — Lang JJ et al. Cardiorespiratory fitness is a strong and consistent predictor of morbidity and mortality among adults: an overview of meta-analyses representing over 20.9 million observations from 199 unique cohort studies. Br J Sports Med, 2024. Overview of meta-analyses: higher cardiorespiratory fitness is consistently linked with lower risk of death and disease. PubMed 38599681
  • Review — O’Keefe JH et al. Training Strategies to Optimize Cardiovascular Durability and Life Expectancy. Mo Med, 2023. Narrative review of training approaches for cardiovascular fitness and longevity. PubMed 37091937

Sleep

  • Observational — Windred DP et al. Sleep regularity is a stronger predictor of mortality risk than sleep duration: A prospective cohort study. Sleep, 2024. In UK Biobank, regular sleep timing predicted mortality risk more strongly than sleep duration. PubMed 37738616
  • Observational — Sabia S et al. Association of sleep duration in middle and old age with incidence of dementia. Nat Commun, 2021. Short sleep in mid-life was associated with higher later dementia risk in the Whitehall II cohort. PubMed 33879784

Nutrition and fasting

  • Human RCT (secondary analysis) — Waziry R et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nat Aging, 2023. CALERIE: two years of modest calorie restriction in healthy adults slowed DunedinPACE slightly but did not change other aging clocks (PhenoAge, GrimAge). PubMed 37118425
  • Animal — Di Francesco A et al. Dietary restriction impacts health and lifespan of genetically diverse mice. Nature, 2024. In 960 genetically diverse female mice, calorie restriction and fasting extended lifespan in proportion to the degree of restriction, but genetics influenced lifespan more than diet. PubMed 39385029
  • Human RCT — Liu D et al. Calorie Restriction with or without Time-Restricted Eating in Weight Loss. N Engl J Med, 2022. Time-restricted eating added to calorie restriction did not produce more weight loss than calorie restriction alone over one year. PubMed 35443107

HBOT and telomeres

Some clinics, including NCFM, offer services related to this topic. The research below is not evidence that any NCFM service will slow aging or produce these results for you.

  • Early human (uncontrolled) — Hachmo Y et al. Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. Aging (Albany NY), 2020. Small study of 35 adults aged 64+ reporting longer telomeres in blood cells after a 60-session HBOT protocol; no control group. Several authors worked for or held shares in an HBOT company. Telomere changes in blood cells have not been shown to mean slower aging. PubMed 33206062
  • Early (case report, 1 person) — Maroon JC The effect of hyperbaric oxygen therapy on cognition, performance, proteomics, and telomere length-The difference between zero and one: A case report. Front Neurol, 2022. A neurosurgeon’s report on his own 60 HBOT sessions; a single case cannot show cause and effect. PubMed 35968296

Brain aging

  • Meta-analysis of RCTs — Mendes AJ et al. Single-domain and multidomain lifestyle interventions for the prevention of cognitive decline in older adults who are cognitively unimpaired: a systematic review and network meta-analysis. Lancet Healthy Longev, 2025. Meta-analysis of single- and multidomain lifestyle programs for cognition in older adults. PubMed 41016407
  • Human RCT — Baker LD et al. Structured vs Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function: The US POINTER Randomized Clinical Trial. JAMA, 2025. U.S. POINTER: structured lifestyle program produced modestly greater cognitive gains than a self-guided one. PubMed 40720610

Peptides

Some clinics, including NCFM, offer services related to this topic. The research below is not evidence that any NCFM service will slow aging or produce these results for you.

  • Review (mostly animal evidence) — Vasireddi N et al. Emerging Use of BPC-157 in Orthopaedic Sports Medicine: A Systematic Review. HSS J, 2025. Systematic review of BPC-157 in sports medicine: evidence is mostly animal studies, with very little human data. BPC-157 is not FDA-approved and is banned in professional sports. PubMed 40756949
  • Review (early / animal) — Mohtashami Z et al. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. Int J Mol Sci, 2022. Review of MOTS-c, a mitochondria-derived peptide studied in aging, largely in laboratory research. PubMed 36233287

This page summarizes published research for educational purposes. It is not a list of NCFM treatments or offerings, and it makes no claim that any NCFM therapy slows or reverses aging. Many findings come from animal, small or observational studies, and results may not apply to you. Talk with a physician before acting on any research.

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