{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:07:22Z","timestamp":1782976042463,"version":"3.54.5"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aging is an irreversible process shaped by genetic and environmental factors. Beyond physical and mental decline, it involves complex biological mechanisms. Programmed theories propose aging follows a biological clock, while error theories attribute it to environmental damage. A key mechanism is telomere shortening; once critically shortened, cells enter senescence. Telomerase preserves telomeres, but its activity decreases with age. Aging also causes cognitive decline, measurable through tools like electroencephalography (EEG).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>\n                      This two-arm, double blind, placebo-controlled superiority randomized controlled trial evaluates the effects of\n                      <jats:italic>Bacopa monnieri<\/jats:italic>\n                      freeze-dried herbal decoction (BMFD) on aging and cognition. Elderly participants (MoCA \u226524) will be randomized to receive BMFD or placebo, administered as 120\u202fmL twice daily for 45\u202fdays, with assessments at baseline, 45, and 90\u202fdays. Conducted at the Clinical Trial Center, Faculty of Indigenous Medicine, University of Colombo, the trial tests BMFD\u2019s ability to stabilize aging processes and enhance neurocognitive functions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>Primary outcomes include telomerase activity and telomere length (qPCR). Secondary outcomes include neurocognitive function [validated MoCA for the Sri Lankan population], neurophysiological functions\u2014nerve conduction test (NCT) for upper and lower limb nerves and brain electrical activity (EEG)\u2014and assessing health-related quality of life (HRQoL) using a validated questionnaire.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      This trial will provide evidence on BMFD\u2019s potential to preserve telomere length, support cognitive functions, and slow aging processes. Integrating Ayurvedic principles, including constitution (\n                      <jats:italic>Prakriti<\/jats:italic>\n                      ), it aims to enable early detection of cognitive decline and aging-related changes. Findings are expected to inform preventive and personalized strategies, contributing to evidence-based applications of\n                      <jats:italic>Bacopa monnieri<\/jats:italic>\n                      in healthy aging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:uri>https:\/\/doi.org\/10.1186\/ISRCTN64126920<\/jats:uri>\n                      , identifier ISRCTN64126920.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1702773","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T13:03:55Z","timestamp":1772111035000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Bacopa monnieri herbal supplement on aging and neurocognitive functions, including neurophysiological assessments, in relation to constitution (Prakriti) in healthy adults: clinical trial protocol"],"prefix":"10.3389","volume":"13","author":[{"given":"H. L. N. R.","family":"Pradeep","sequence":"first","affiliation":[{"name":"Department of Basic Principles, Ayurveda Anatomy and Physiology, Faculty of Indigenous Medicine, University of Colombo","place":["Colombo, Sri Lanka"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. K.","family":"Perera","sequence":"additional","affiliation":[{"name":"Department of Ayurveda Pharmacology, Pharmaceutics and Community Medicine, Faculty of Indigenous Medicine, University of Colombo","place":["Colombo, Sri Lanka"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. R.","family":"Waratenne","sequence":"additional","affiliation":[{"name":"Department of Basic Principles, Ayurveda Anatomy and Physiology, Faculty of Indigenous Medicine, University of Colombo","place":["Colombo, Sri Lanka"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Samaranayake","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine, University of Colombo","place":["Colombo, Sri Lanka"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. D. N.","family":"Dissanayake","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Colombo","place":["Colombo, Sri Lanka"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/s0921-8734(96)90005-3","article-title":"A network theory of ageing: the interactions of defective mitochondria, aberrant proteins, free radicals and scavengers in the ageing process","volume":"316","author":"Kowald","year":"1996","journal-title":"Mutat Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1152\/japplphysiol.00288.2003","article-title":"Invited review: theories of aging","volume":"95","author":"Weinert","year":"2003","journal-title":"J Appl Physiol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.18632\/aging.206254","article-title":"Update on the detection of frailty in older adults: a multicenter cohort machine learning-based study protocol","volume":"17","author":"Fern\u00e1ndez-Carnero","year":"2025","journal-title":"Aging (Albany NY)"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"5919","DOI":"10.1016\/s0021-9258(19)39264-6","article-title":"Telomeres: structure and synthesis","volume":"265","author":"Blackburn","year":"1990","journal-title":"J Biol Chem"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/35040500","article-title":"Telomere states and cell fates","volume":"408","author":"Blackburn","year":"2000","journal-title":"Nature"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.1073\/pnas.91.8.2882","article-title":"Activation of telomerase in a human tumor","volume":"91","author":"de Lange","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"5609","DOI":"10.1093\/nar\/gkq370","article-title":"InTERTpreting telomerase structure and function","volume":"38","author":"Wyatt","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1126\/science.279.5349.349","article-title":"Extension of life-span by introduction of telomerase into normal human cells","volume":"279","author":"Bodnar","year":"1998","journal-title":"Science"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s004390050711","article-title":"Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals","volume":"102","author":"Iwama","year":"1998","journal-title":"Hum Genet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1136\/jmg.36.6.494","article-title":"Simultaneous decrease of telomere length and telomerase activity with ageing of human amniotic fluid cells","volume":"36","author":"Mosquera","year":"1999","journal-title":"J Med Genet"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.4049\/jimmunol.165.3.1191","article-title":"Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age","volume":"165","author":"Son","year":"2000","journal-title":"J Immunol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1093\/nar\/gkg208","article-title":"Ageing and telomeres: a study into organ- and gender-specific telomere shortening","volume":"31","author":"Cherif","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1002\/(sici)1520-6408(1996)18:2<>3.0.co;2-3","article-title":"Telomerase activity in human germline and embryonic tissues and cells","volume":"18","author":"Wright","year":"1996","journal-title":"Dev Genet"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1354\/vp.37-2-177","article-title":"Cellular proliferative and telomerase activity in canine mammary gland tumors","volume":"37","author":"Funakoshi","year":"2000","journal-title":"Vet Pathol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.jalz.2009.05.666","article-title":"Comparisons of telomere lengths in peripheral blood and cerebellum in Alzheimer's disease","volume":"5","author":"Lukens","year":"2009","journal-title":"Alzheimers Dement"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1479-5876-6-48","article-title":"Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda","volume":"6","author":"Prasher","year":"2008","journal-title":"J Transl Med"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1371\/journal.pone.0045752","article-title":"Potential of ayurgenomics approach in predicting susceptibility to complex disorders","volume":"16","author":"Juyal","year":"2012","journal-title":"OMICS"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"15786","DOI":"10.1038\/srep15786","article-title":"Genome-wide analysis correlates Ayurvedic Prakriti","volume":"5","author":"Govindaraj","year":"2015","journal-title":"Sci Rep"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.jaim.2017.05.004","article-title":"Association between Prakriti and risk of type 2 diabetes: a cross-sectional observational study","volume":"8","author":"Tiwari","year":"2017","journal-title":"J Ayurveda Integr Med"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"494","DOI":"10.4103\/0974-8520.96122","article-title":"Ayurvedic Prakriti and their cardiovascular disease risk profiles","volume":"32","author":"Shilpa","year":"2011","journal-title":"Ayu"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"238","DOI":"10.4103\/0974-8520.105244","article-title":"Association of ayurvedic constitution (Prakriti) with arterial stiffness, inflammatory markers, and metabolic traits","volume":"33","author":"Mahalle","year":"2012","journal-title":"Ayu"},{"key":"ref22","first-page":"95","volume-title":"Charaka Samhita, Vimana Sthana (Sharma RK, Dash V, translators)","author":"Charaka","year":"2014"},{"key":"ref23","volume-title":"Sushruta Samhita, Sharira Sthana (Srikantha Murthy KR, translator)","author":"Sushruta","year":"2012"},{"key":"ref24","volume-title":"Ashtanga Hridaya, Sharira Sthana, Chapter 3. (Srikantha Murthy KR, translator)","author":"Vagbhata","year":"2012"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e70125","DOI":"10.1111\/1756-185X.70125","article-title":"Fourteen-year retrospective cohort study on the impact of climatic factors on chronic musculoskeletal pain: a Spanish primary care analysis","volume":"28","author":"Cuenca-Zald\u00edvar","year":"2025","journal-title":"Int J Rheum Dis"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.neulet.2010.05.037","article-title":"Age-dependent features of EEG-reactivity\u2014spectral, complexity, and network characteristics","volume":"479","author":"Ga\u00e1l","year":"2010","journal-title":"Neurosci Lett"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"R80","DOI":"10.1016\/j.cub.2018.11.052","article-title":"Electroencephalography","volume":"29","author":"Biasiucci","year":"2019","journal-title":"Curr Biol"},{"key":"ref28","volume-title":"Electroencephalography: Basic principles, clinical applications, and related fields","author":"Niedermeyer","year":"2005"},{"key":"ref29","doi-asserted-by":"crossref","DOI":"10.1093\/acprof:oso\/9780195301069.001.0001","volume-title":"Rhythms of the brain","author":"Buzs\u00e1ki","year":"2006"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1111\/psyp.12043","article-title":"Peak individual alpha frequency qualifies as a stable neurophysiological trait marker in healthy younger and older adults","volume":"50","author":"Grandy","year":"2013","journal-title":"Psychophysiology"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"766","DOI":"10.3389\/fnhum.2013.00766","article-title":"An algorithm for the EEG frequency architecture of consciousness and brain body coupling","volume":"7","author":"Klimesch","year":"2013","journal-title":"Front Hum Neurosci"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1111\/bph.13882","article-title":"The concise guide to pharmacology 2017\/18: overview","volume":"174","author":"Alexander","year":"2017","journal-title":"Br J Pharmacol"},{"key":"ref33","first-page":"161","article-title":"Ayurveda and geriatric health care: a comprehensive review","volume":"6","author":"Sharma","year":"2015","journal-title":"J Ayurveda Integr Med"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"R741","DOI":"10.1016\/j.cub.2012.07.024","article-title":"Ageing as a risk factor for disease","volume":"22","author":"Niccoli","year":"2012","journal-title":"Curr Biol"},{"key":"ref35","volume-title":"Ageing and health","year":"2025"},{"key":"ref36","volume-title":"Elderly population","year":"2025"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1097\/j.pain.0000000000003627","article-title":"Can quantitative sensory testing predict treatment outcomes in hip and knee osteoarthritis? A systematic review and meta-analysis of individual participant data","volume":"166","author":"Murphy","year":"2025","journal-title":"Pain"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.phymed.2003.12.008","article-title":"Bacopa monniera, a reputed nootropic plant: an overview","volume":"12","author":"Russo","year":"2005","journal-title":"Phytomedicine"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1002\/ptr.2073","article-title":"Protective activity of Bacopa monniera Linn. On nicotine-induced toxicity in mice","volume":"21","author":"Vijayan","year":"2007","journal-title":"Phytother Res"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"264","DOI":"10.3390\/nu17020264","article-title":"Relationship between the gut microbiome, tryptophan-derived metabolites, and osteoarthritis-related pain: a systematic review with meta-analysis","volume":"17","author":"Mel\u00e9ndez-Oliva","year":"2025","journal-title":"Nutrients"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/S1470-2045(13)70366-8","article-title":"Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study","volume":"14","author":"Ornish","year":"2013","journal-title":"Lancet Oncol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.4038\/cmj.v56i4.3892","article-title":"Validation of the Sinhala version of the Montreal cognitive assessment in screening for dementia","volume":"56","author":"Karunaratne","year":"2011","journal-title":"Ceylon Med J"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1093\/occmed\/kqv078","article-title":"The Montreal cognitive assessment (MoCA)","volume":"65","author":"Hobson","year":"2015","journal-title":"Occup Med"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J Am Geriatr Soc"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"789","DOI":"10.3233\/JAD-161042","article-title":"Cross-cultural applicability of the Montreal cognitive assessment (MoCA): a systematic review","volume":"58","author":"O\u2019Driscoll","year":"2017","journal-title":"J Alzheimer's Dis"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1212\/WNL.0b013e318230208a","article-title":"Normative data for the Montreal cognitive assessment (MoCA) in a population-based sample","volume":"77","author":"Rossetti","year":"2011","journal-title":"Neurology"},{"key":"ref47","volume-title":"Ayurveda Aushadha Sangrahaya","year":"1976"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"Cell"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"367","DOI":"10.14336\/AD.2018.0324","article-title":"Redefining chronic inflammation in aging and age-related diseases: proposal of the Seno-inflammation concept","volume":"10","author":"Chung","year":"2019","journal-title":"Aging Dis"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"644123","DOI":"10.3389\/fgene.2021.644123","article-title":"Ayurgenomics: a systems biology approach for integrating Ayurveda and genomics","volume":"12","author":"Sanghavi","year":"2021","journal-title":"Front Genet"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"13176","DOI":"10.18632\/aging.206162","article-title":"Addressing frailty in older adults: an integrated challenge for health, science, and society","volume":"16","author":"Fern\u00e1ndez-Carnero","year":"2024","journal-title":"Aging (Albany NY)"},{"key":"ref9001","doi-asserted-by":"crossref","first-page":"260","DOI":"10.2478\/sjph-2021-0035","article-title":"A questionnaire for rating health\u2011related quality of life","volume":"60","author":"Jankovi\u0107","year":"2021","journal-title":"Slovenian Journal of Public Health"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1702773\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T13:03:57Z","timestamp":1772111037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1702773\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":52,"alternative-id":["10.3389\/fmed.2026.1702773"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1702773","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]},"article-number":"1702773"}}