Lifestyle Changes in Aging and their Potential Impact on POAG

Abstract

Primary open angle glaucoma is a primary mitochondrial disease with oxidative stress triggering neuroinflammation, eventually resulting in neurodegeneration. This affects many other areas of the brain in addition to the visual system. Aging also leads to inflammaging – a low-grade chronic inflammatory reaction in mitochondrial dysfunction, so these inflammatory processes overlap in the aging process and intensify pathophysiological processes associated with glaucoma. Actively counteracting these inflammatory events involves optimising treatment for any manifest systemic diseases while maintaining chronobiology and improving the microbiome. Physical and mental activity also provides support. This requires a holistic approach towards optimising neurodegeneration treatment in primary open angle glaucoma in addition to reducing intraocular pressure according personalised patient targets.

Fazit

Bereits bekannt:

• Erhöhtes Alter ist ein Risikofaktor für das POWG.

• Das Älterwerden ist ein sehr komplexer Prozess.

• Bekannte Maßnahmen zur Verlangsamung des Alterns sind eine optimale Therapieeinstellung der vorliegenden Systemerkrankungen sowie physische und mentale Aktivität.

Neu beschrieben:

• Das POWG zählt zu den neurodegenerativen Erkrankungen.

• Das Altern führt zu einer chronischen subklinischen Entzündung (Inflamm-Aging).

• Neue Schwerpunkte zur Verlangsamung des Alterns sind eine Einhaltung von chronobiologischen Abläufen und die Aufrechterhaltung eines gesunden enteralen Mikrobioms.

Conclusion

Already known:

• Increased age is a risk factor for POAG.

• Aging is a highly complex process.

• Familiar measures towards slowing down aging include optimised therapy for manifest systemic diseases as well as physical and mental activity.

New:

• POAG is a neurodegenerative disease.

• Aging leads to chronic subclinical inflammation, known as inflammaging.

• New areas of focus for slowing down aging include maintaining chronobiological processes and maintaining a healthy enteral microbiome.

Keywords

Glaucoma - aging - neurodegeneration - chronobiology - microbiome - physical activity

Publikationsverlauf

Eingereicht: 17. Dezember 2023

Angenommen: 19. Juli 2024

Artikel online veröffentlicht:
27. August 2024

• References/Literatur

• 1 Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006; 90: 262-267 DOI: 10.1136/bjo.2005.081224.
• 2 Prokosch V, Zwingelberg SB, Mercieca K. Normaldruckglaukome. Klin Monbl Augenheilkd 2022; DOI: 10.1055/a-1758-3486.
• 3 Leung DYL, Tham CC. Normal-tension glaucoma: Current concepts and approaches - A review. Clin Exp Ophthalmol 2022; 50: 247-259 DOI: 10.1111/ceo.14043.
• 4 Jassim AH, Inman DM, Mitchell CH. Crosstalk Between Dysfunctional Mitochondria and Inflammation in Glaucomatous Neurodegeneration. Front Pharmacol 2021; 12: 699623 DOI: 10.3389/fphar.2021.699623.
• 5 Duarte JN. Neuroinflammatory Mechanisms of Mitochondrial Dysfunction and Neurodegeneration in Glaucoma. J Ophthalmol 2021; 2021: 4581909 DOI: 10.1155/2021/4581909.
• 6 Abu-Amero KK, Morales J, Bosley TM. Mitochondrial abnormalities in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci 2006; 47: 2533-2541 DOI: 10.1167/iovs.05-1639.
• 7 Bosley TM, Hellani A, Spaeth GL. et al. Down-regulation of OPA1 in patients with primary open angle glaucoma. Mol Vis 2011; 17: 1074-1079
• 8 Fourgeux C, Martine L, Björkhem I. et al. Primary open-angle glaucoma: association with cholesterol 24S-hydroxylase (CYP46A1) gene polymorphism and plasma 24-hydroxycholesterol levels. Invest Ophthalmol Vis Sci 2009; 50: 5712-5717 DOI: 10.1167/iovs.09-3655.
• 9 Geto Z, Molla MD, Challa F. et al. Mitochondrial Dynamic Dysfunction as a Main Triggering Factor for Inflammation Associated Chronic Non-Communicable Diseases. J Inflamm Res 2020; 13: 97-107 DOI: 10.2147/JIR.S232009.
• 10 Baudouin C, Kolko M, Melik-Parsadaniantz S. et al. Inflammation in Glaucoma: From the back to the front of the eye, and beyond. Prog Retin Eye Res 2021; 83: 100916 DOI: 10.1016/j.preteyeres.2020.100916.
• 11 Vernazza S, Tirendi S, Bassi AM. et al. Neuroinflammation in Primary Open-Angle Glaucoma. J Clin Med 2020; 9: 3172 DOI: 10.3390/jcm9103172.
• 12 Chan JW, Chan NCY, Sadun AA. Glaucoma as Neurodegeneration in the Brain. Eye Brain 2021; 13: 21-28 DOI: 10.2147/EB.S293765.
• 13 Erb C, Gast U, Schremmer D. German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin Exp Ophthalmol 2008; 246: 1593-1601 DOI: 10.1007/s00417-008-0881-9.
• 14 Lin HC, Chien CW, Hu CC. et al. Comparison of comorbid conditions between open-angle glaucoma patients and a control cohort: a case-control study. Ophthalmology 2010; 117: 2088-2095 DOI: 10.1016/j.ophtha.2010.03.003.
• 15 Touyz RM, Rios FJ, Alves-Lopes R. et al. Oxidative Stress: A Unifying Paradigm in Hypertension. Can J Cardiol 2020; 36: 659-670 DOI: 10.1016/j.cjca.2020.02.081.
• 16 Miller YI, Shyy JY. Context-Dependent Role of Oxidized Lipids and Lipoproteins in Inflammation. Trends Endocrinol Metab 2017; 28: 143-152 DOI: 10.1016/j.tem.2016.11.002.
• 17 Burgos-Morón E, Abad-Jiménez Z, Marañón AM. et al. Relationship Between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues. J Clin Med 2019; 8: 1385 DOI: 10.1016/j.tem.2016.11.002.
• 18 Gupta N, Ang LC, Noël de Tilly L. et al. Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Br J Ophthalmol 2006; 90: 674-678 DOI: 10.1136/bjo.2005.086769.
• 19 Sabel BA, Lehnigk L. Is Mental Stress the Primary Cause of Glaucoma?. Klin Monbl Augenheilkd 2021; 238: 132-145 DOI: 10.1055/a-1303-8025.
• 20 Gegenfurtner KR, Walter S, Braun DI. Visuelle Informationsverarbeitung im Gehirn. In: Huber HD, Lockermann B, Scheibel M. Hrsg. Bild | Medien | Wissen. Visuelle Kompetenz im Medienzeitalter. München: Kopaed; 2002
• 21 Erb C. Funktionelle Störungen im zeitlichen Verlauf der Glaukomerkrankung. Ophthalmologe 2015; 112: 402-409 DOI: 10.1007/s00347-015-0005-y.
• 22 Berdahl JP, Fautsch MP, Stinnett SS. et al. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study. Invest Ophthalmol Vis Sci 2008; 49: 5412-5418 DOI: 10.1167/iovs.08-2228.
• 23 Jonas JB, Wang N, Yang D. et al. Facts and myths of cerebrospinal fluid pressure for the physiology of the eye. Prog Retin Eye Res 2015; 46: 67-83 DOI: 10.1016/j.preteyeres.2015.01.002.
• 24 Killer HE. Compartment syndromes of the optic nerve and open-angle glaucoma. J Glaucoma 2013; 22 (Suppl. 5) S19-S20 DOI: 10.1097/IJG.0b013e3182934a0f.
• 25 Wostyn P, Van Dam D, Audenaert K. et al. A new glaucoma hypothesis: a role of glymphatic system dysfunction. Fluids Barriers CNS 2015; 12: 16 DOI: 10.1186/s12987-015-0012-z.
• 26 Criscuolo C, Fabiani C, Cerri E. et al. Synaptic Dysfunction in Alzheimerʼs Disease and Glaucoma: From Common Degenerative Mechanisms Toward Neuroprotection. Front Cell Neurosci 2017; 11: 53 DOI: 10.3389/fncel.2017.00053.
• 27 Ramirez AI, de Hoz R, Salobrar-Garcia E. et al. The Role of Microglia in Retinal Neurodegeneration: Alzheimerʼs Disease, Parkinson, and Glaucoma. Front Aging Neurosci 2017; 9: 214 DOI: 10.3389/fnagi.2017.00214.
• 28 Erb C. Sekundäre Neuroprotektion beim Glaukom durch ergänzende medikamentöse Therapiekonzepte. Klin Monbl Augenheilkd 2020; 237: 163-174 DOI: 10.1055/a-1093-0945.
• 29 Crump C, Sundquist J, Sieh W. et al. Risk of Alzheimerʼs Disease and Related Dementias in Persons With Glaucoma: A National Cohort Study. Ophthalmology 2024; 131: 302-309 DOI: 10.1016/j.ophtha.2023.10.014.
• 30 Gallo Afflitto G, Aiello F, Cesareo M. et al. Primary Open Angle Glaucoma Prevalence in Europe: A Systematic Review and Meta-Analysis. J Glaucoma 2022; 31: 783-788 DOI: 10.1097/IJG.0000000000002083.
• 31 Kapetanakis VV, Chan MP, Foster PJ. et al. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta- analysis. Br J Ophthalmol 2016; 100: 86-93 DOI: 10.1136/bjophthalmol-2015-307223.
• 32 Hou Y, Dan X, Babbar M. et al. Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 2019; 15: 565-581 DOI: 10.1038/s41582-019-0244-7.
• 33 Schmauck-Medina T, Molière A, Lautrup S. et al. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging (Albany NY) 2022; 14: 6829-6839 DOI: 10.18632/aging.204248.
• 34 Saavedra D, Añé-Kourí AL, Barzilai N. et al. Aging and chronic inflammation: highlights from a multidisciplinary workshop. Immun Ageing 2023; 20: 25 DOI: 10.1186/s12979-023-00352-w.
• 35 Chaudhary MR, Chaudhary S, Sharma Y. et al. Aging, oxidative stress and degenerative diseases: mechanisms, complications and emerging therapeutic strategies. Biogerontology 2023; 24: 609-662 DOI: 10.1007/s10522-023-10050-1.
• 36 Boersma P, Black LI, Ward BW. Prevalence of Multiple Chronic Conditions Among US Adults, 2018. Prev Chronic Dis 2020; 17: E106 DOI: 10.5888/pcd17.200130.
• 37 Cohen AA, Kennedy BK, Anglas U. et al. Lack of consensus on an aging biology paradigm? A global survey reveals an agreement to disagree, and the need for an interdisciplinary framework. Mech Ageing Dev 2020; 191: 111316 DOI: 10.1016/j.mad.2020.111316.
• 38 Belsky DW, Caspi A, Houts R. et al. Quantification of biological aging in young adults. Proc Natl Acad Sci U S A 2015; 112 (30) E4104-4110 DOI: 10.1073/pnas.1506264112.
• 39 Herst PM, Rowe MR, Carson GM. et al. Functional mitochondria in health and disease. Front Endocrinol (Lausanne) 2017; 8: 296 DOI: 10.3389/fendo.2017.00296.
• 40 Lane N. Why is life the way it is?. Mol Front J 2019; 03: 20-28
• 41 Littarru GP, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol 2007; 37: 31-37 DOI: 10.1007/s12033-007-0052-y.
• 42 Kalén A, Appelkvist EL, Dallner G. Age-related changes in the lipid compositions of rat and human tissues. Lipids 1989; 24: 579-584 DOI: 10.1007/BF02535072.
• 43 Qu J, Kaufman Y, Washington I. Coenzyme Q10 in the human retina. Invest Ophthalmol Vis Sci 2009; 50: 1814-1818 DOI: 10.1167/iovs.08-2656.
• 44 Guarner V, Rubio-Ruiz ME. Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease. Interdiscip Top Gerontol 2015; 40: 99-106 DOI: 10.1159/000364934.
• 45 Erb C, Gast U, Schremmer D. German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin Exp Ophthalmol 2008; 246: 1593-1601 DOI: 10.1007/s00417-008-0881-9.
• 46 Lin HC, Chien CW, Hu CC. et al. Comparison of comorbid conditions between open angle glaucoma patients and a control cohort: a case control study. Ophthalmology 2010; 117: 2088-2095 DOI: 10.1016/j.ophtha.2010.03.003.
• 47 Hacke C, Erb C, Weisser B. Risikofaktoren und Zielwerte in der kardiovaskulären Primär- und Sekundärprävention: Bedeutung für das Glaukom. Klin Monbl Augenheilkd 2018; 235: 151-156 DOI: 10.1055/s-0044-101260.
• 48 Bowe A, Grünig M, Schubert J. et al. Circadian Variation in Arterial Blood Pressure and Glaucomatous Optic Neuropathy–A Systematic Review and Meta-Analysis. Am J Hypertens 2015; 28: 1077-1082 DOI: 10.1093/ajh/hpv016.
• 49 Qiu C, von Strauss E, Fastbom J. et al. Low blood pressure and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Arch Neurol 2003; 60: 223-228 DOI: 10.1001/archneur.60.2.223.
• 50 Freeman R, Abuzinadah AR, Gibbons C. et al. Orthostatic Hypotension: JACC State-of-the-Art Review. J Am Coll Cardiol 2018; 72: 1294-1309 DOI: 10.1016/j.jacc.2018.05.079.
• 51 Bundesärztekammer, Kassenärztliche Bundesvereinigung, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften. Nationale VersorgungsLeitlinie Typ-2-Diabetes. 2. Auflage, Version 3.0, AWMF-Register-Nr. nvl-001, 2023. Im Internet (Stand: 26.08.2024): https://www.leitlinien.de/themen/diabetes/version-3
• 52 LeRoith D, Biessels GJ, Braithwaite SS. et al. Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab 2019; 104: 1520-1574 DOI: 10.1210/jc.2019-00198.
• 53 Mach F, Baigent C, Catapano AL. et al. ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41: 111-188 DOI: 10.1093/eurheartj/ehz455.
• 54 Cedernaes J, Waldeck N, Bass J. Neurogenetic basis for circadian regulation of metabolism by the hypothalamus. Genes Dev 2019; 33: 1136-1158 DOI: 10.1101/gad.328633.119.
• 55 Verma AK, Khan MI, Ashfaq F. et al. Crosstalk between aging, circadian rhythm, and melatonin. Rejuvenation Res 2023; 26: 229-241 DOI: 10.1089/rej.2023.0047.
• 56 Chen R, Routh BN, Gaudet AD. et al. Circadian Regulation of the Neuroimmune Environment Across the Lifespan: From Brain Development to Aging. J Biol Rhythms 2023; 38: 419-446 DOI: 10.1177/07487304231178950.
• 57 Canever JB, Queiroz LY, Soares ES. et al. Circadian rhythm alterations affecting the pathology of neurodegenerative diseases. J Neurochem 2023; DOI: 10.1111/jnc.15883.
• 58 Bitar RD, Torres-Garza JL, Reiter RJ. et al. Neural glymphatic system: Clinical implications and potential importance of melatonin. Melatonin Research 2021; 4: 551-565 DOI: 10.32794/mr112500111.
• 59 Ding Z, Fan X, Zhang Y. et al. The glymphatic system: a new perspective on brain diseases. Front Aging Neurosci 2023; 15: 1179988 DOI: 10.3389/fnagi.2023.1179988.
• 60 Reiter RJ, Sharma R, Cucielo MS. et al. Brain washing and neural health: role of age, sleep, and the cerebrospinal fluid melatonin rhythm. Cell Mol Life Sci 2023; 80: 88 DOI: 10.1007/s00018-023-04736-5.
• 61 Martín Giménez VM, de Las Heras N, Ferder L. et al. Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction during a Cytokine Storm Typical of Oxidative/Inflammatory Diseases. Diseases 2021; 9: 30 DOI: 10.3390/diseases9020030.
• 62 Kopeć K, Szleszkowski S, Koziorowski D. et al. Glymphatic System and Mitochondrial Dysfunction as Two Crucial Players in Pathophysiology of Neurodegenerative Disorders. Int J Mol Sci 2023; 24: 10366 DOI: 10.3390/ijms241210366.
• 63 Casagrande M, Forte G, Favieri F. et al. Sleep Quality and Aging: A Systematic Review on Healthy Older People, Mild Cognitive Impairment and Alzheimerʼs Disease. Int J Environ Res Public Health 2022; 19: 8457 DOI: 10.3390/ijerph19148457.
• 64 Watson NF, Badr MS, Belenky G. et al. Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society. Sleep 2015; 38: 843-844 DOI: 10.5665/sleep.4716.
• 65 Ferrie JE, Shipley MJ, Cappuccio FP. et al. A prospective study of change in sleep duration: associations with mortality in the Whitehall II cohort. Sleep 2007; 30: 1659-1666 DOI: 10.1093/sleep/30.12.1659.
• 66 Anghel L, Ciubară A, Nechita A. et al. Sleep Disorders Associated with Neurodegenerative Diseases. Diagnostics (Basel) 2023; 13: 2898 DOI: 10.3390/diagnostics13182898.
• 67 Giese M, Unternaehrer E, Brand S. et al. The interplay of stress and sleep impacts BDNF level. PLoS One 2013; 8: e76050 DOI: 10.1371/journal.pone.0076050.
• 68 Colucci-DʼAmato L, Speranza L, Volpicelli F. Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. Int J Mol Sci 2020; 21: 7777 DOI: 10.3390/ijms21207777.
• 69 Pisani A, Paciello F, Del Vecchio V. et al. The Role of BDNF as a Biomarker in Cognitive and Sensory Neurodegeneration. J Pers Med 2023; 13: 652 DOI: 10.3390/jpm13040652.
• 70 Tang Y, Shi J, Chen LH. et al. From visual disorder to mental disturbance: How does glaucoma disrupt circadian rhythm?. Life Res 2022; 5: 9 DOI: 10.53388/2021-1119-301.
• 71 Gao J, Provencio I, Liu X. Intrinsically photosensitive retinal ganglion cells in glaucoma. Front Cell Neurosci 2022; 16: 992747 DOI: 10.3389/fncel.2022.992747.
• 72 Martínez-Águila A, Martín-Gil A, Carpena-Torres C. et al. Influence of Circadian Rhythm in the Eye: Significance of Melatonin in Glaucoma. Biomolecules 2021; 11: 340 DOI: 10.3390/biom11030340.
• 73 Lambuk L, Mohd Lazaldin MA, Ahmad S. et al. Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in Glaucoma: A Review of Current State of the Art. Front Pharmacol 2022; 13: 875662 DOI: 10.3389/fphar.2022.875662.
• 74 Oda H. Chrononutrition. J Nutr Sci Vitaminol (Tokyo) 2015; 61 (Suppl.) S92-S94 DOI: 10.3177/jnsv.61.S92.
• 75 Franzago M, Alessandrelli E, Notarangelo S. et al. Chrono-Nutrition: Circadian Rhythm and Personalized Nutrition. Int J Mol Sci 2023; 24: 2571 DOI: 10.3390/ijms24032571.
• 76 Gilbert JA, Blaser MJ, Caporaso JG. et al. Current understanding of the human microbiome. Nat Med 2018; 24: 392-400 DOI: 10.1038/nm.4517.
• 77 Osadchiy V, Martin CR, Mayer EA. The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical Implications. Clin Gastroenterol Hepatol 2019; 17: 322-332 DOI: 10.1016/j.cgh.2018.10.002.
• 78 Mayer EA, Nance K, Chen S. The Gut-Brain Axis. Annu Rev Med 2022; 73: 439-453 DOI: 10.1146/annurev-med-042320-014032.
• 79 Hu X, Fan Y, Li H. et al. Impacts of Cigarette Smoking Status on Metabolomic and Gut Microbiota Profile in Male Patients With Coronary Artery Disease: A Multi Omics Study. Front Cardiovasc Med 2021; 8: 766739 DOI: 10.3389/fcvm.2021.766739.
• 80 Khan MF, Wang H. Environmental Exposures and Autoimmune Diseases: Contribution of Gut Microbiome. Front Immunol 2020; 10: 3094 DOI: 10.3389/fimmu.2019.03094.
• 81 Hartmann P, Seebauer CT, Schnabl B. Alcoholic liver disease: the gut microbiome and liver cross talk. Alcohol Clin Exp Res 2015; 39: 763-775 DOI: 10.1111/acer.12704.
• 82 Dong TS, Gupta A. Influence of Early Life, Diet, and the Environment on the Microbiome. Clin Gastroenterol Hepatol 2019; 17: 231-242 DOI: 10.1016/j.cgh.2018.08.067.
• 83 Rekha K, Venkidasamy B, Samynathan R. et al. Short chain fatty acid: An updated review on signaling, metabolism, and therapeutic effects. Crit Rev Food Sci Nutr 2024; 64: 2461-2489 DOI: 10.1080/10408398.2022.2124231.
• 84 Vijay N, Morris ME. Role of monocarboxylate transporters in drug delivery to the brain. Curr Pharm Des 2014; 20: 1487-1498 DOI: 10.2174/13816128113199990462.
• 85 Byrne CS, Chambers ES, Morrison DJ. et al. The role of short chain fatty acids in appetite regulation and energy homeostasis. Int J Obes (Lond) 2015; 39: 1331-1338 DOI: 10.1038/ijo.2015.84.
• 86 Mansuy Aubert V, Ravussin Y. Short chain fatty acids: the messengers from down below. Front Neurosci 2023; 17: 1197759 DOI: 10.3389/fnins.2023.1197759.
• 87 Canfora EE, Meex RCR, Venema K. et al. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol 2019; 15: 261-273 DOI: 10.1038/s41574-019-0156-z.
• 88 Rasouli-Saravani A, Jahankhani K, Moradi S. et al. Role of microbiota short chain fatty acids in the pathogenesis of autoimmune diseases. Biomed Pharmacother 2023; 162: 114620 DOI: 10.1016/j.biopha.2023.114620.
• 89 Wu J, Yang K, Fan H. et al. Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2023; 14: 1114424 DOI: 10.3389/fendo.2023.1114424.
• 90 OʼDonnell JA, Zheng T, Meric G. et al. The gut microbiome and hypertension. Nat Rev Nephrol 2023; 19: 153-167 DOI: 10.1038/s41581-022-00654-0.
• 91 Jia X, Xu W, Zhang L, Li X, Wang R, Wu S. Impact of Gut Microbiota and Microbiota Related Metabolites on Hyperlipidemia. Front Cell Infect Microbiol 2021; 11: 634780 (PMID: 34490132)DOI: 10.3389/fcimb.2021.634780.
• 92 Ticinesi A, Tana C, Nouvenne A. The intestinal microbiome and its relevance for functionality in older persons. Curr Opin Clin Nutr Metab Care 2019; 22: 4-12 DOI: 10.1097/MCO.0000000000000521.
• 93 Leite G, Pimentel M, Barlow GM. et al. Age and the aging process significantly alter the small bowel microbiome. Cell Rep 2021; 36: 109765 DOI: 10.1016/j.celrep.2021.109765.
• 94 Holmannova D, Borsky P, Parova H. Non-Genomic Hallmarks of Aging-The Review. Int J Mol Sci 2023; 24: 15468 DOI: 10.3390/ijms242015468.
• 95 Giannos P, Prokopidis K, Isanejad M. et al. Markers of immune dysregulation in response to the ageing gut: insights from aged murine gut microbiota transplants. BMC Gastroenterol 2022; 22: 533 DOI: 10.1186/s12876-022-02613-2.
• 96 Conway J, Duggal NA. Ageing of the gut microbiome: Potential influences on immune senescence and inflammageing. Ageing Res Rev 2021; 68: 101323 DOI: 10.1016/j.arr.2021.101323.
• 97 Alsegiani AS, Shah ZA. The influence of gut microbiota alteration on age-related neuroinflammation and cognitive decline. Neural Regen Res 2022; 17: 2407-2412 DOI: 10.4103/1673-5374.335837.
• 98 Heravi FS, Naseri K, Hu H. Gut Microbiota Composition in Patients with Neurodegenerative Disorders (Parkinsonʼs and Alzheimerʼs) and Healthy Controls: A Systematic Review. Nutrients 2023; 15: 4365 DOI: 10.3390/nu15204365.
• 99 Liu X, Liu Y, Liu J. et al. Correlation between the gut microbiome and neurodegenerative diseases: a review of metagenomics evidence. Neural Regen Res 2024; 19: 833-845 DOI: 10.4103/1673-5374.382223.
• 100 Ezzati Amini E, Moradi Y. Association between helicobacter pylori infection and primary open-angle glaucoma: a systematic review and meta-analysis. BMC Ophthalmol 2023; 23: 374 DOI: 10.1186/s12886-023-03111-z.
• 101 Săsăran MO, Meliţ LE, Dobru ED. MicroRNA Modulation of Host Immune Response and Inflammation triggered by Helicobacter pylori. Int J Mol Sci 2021; 22 (03) 1406 DOI: 10.3390/ijms22031406.
• 102 Di Pierro F. Gut Microbiota Parameters Potentially Useful in Clinical Perspective. Microorganisms 2021; 9: 2402 DOI: 10.3390/microorganisms9112402.
• 103 Kountouras J, Doulberis M, Papaefthymiou A. et al. Controlling the Impact of Helicobacter pylori-Related Hyperhomocysteinemia on Neurodegeneration. Medicina (Kaunas) 2023; 59: 504 DOI: 10.3390/medicina59030504.
• 104 Kountouras J, Boziki M, Polyzos SA. et al. The Emerging Role of Helicobacter Pylori Induced Metabolic Gastrointestinal Dysmotility and Neurodegeneration. Curr Mol Med 2017; 17: 389-404 DOI: 10.2174/1566524018666171219094837.
• 105 Doulberis M, Kotronis G, Gialamprinou D. et al. Alzheimerʼs disease and gastrointestinal microbiota; impact of Helicobacter pylori infection involvement. Int J Neurosci 2021; 131: 289-301 DOI: 10.1080/00207454.2020.1738432.
• 106 Jünemann A, Rejdak R, Hohberger B. Stellenwert vom Homocystein beim Glaukom. Klin Monbl Augenheilkd 2018; 235: 163-174 DOI: 10.1055/s-0044-101621.
• 107 Dong TS, Gupta A. Influence of Early Life, Diet, and the Environment on the Microbiome. Clin Gastroenterol Hepatol 2019; 17: 231-242 DOI: 10.1016/j.cgh.2018.08.067.
• 108 Pollicino F, Veronese N, Dominguez LJ. et al. Mediterranean diet and mitochondria: New findings. Exp Gerontol 2023; 176: 112165 DOI: 10.1016/j.exger.2023.112165.
• 109 Deutsche Gesellschaft für Ernährung e.V.. Hrsg. Gemüse und Obst. 3. Aufl.. Art.-Nr. 123052 Bonn: 2023
• 110 Bucciantini M, Leri M, Nardiello P. et al. Olive Polyphenols: Antioxidant and Anti Inflammatory Properties. Antioxidants (Basel) 2021; 10: 1044 DOI: 10.3390/antiox10071044.
• 111 Blasche S, Kim Y, Mars RAT. et al. Metabolic cooperation and spatiotemporal niche partitioning in a kefir microbial community. Nat Microbiol 2021; 6: 196-208 DOI: 10.1038/s41564-020-00816-5.
• 112 Vieira CP, Rosario AILS, Lelis CA. et al. Bioactive Compounds from Kefir and Their Potential Benefits on Health: A Systematic Review and Meta Analysis. Oxid Med Cell Longev 2021; 2021: 9081738 DOI: 10.1155/2021/9081738.
• 113 German Nutrition Society (DGE). New Reference Values for Vitamin C Intake. Ann Nutr Metab 2015; 67: 13-20 DOI: 10.1159/000434757.
• 114 Zheng X, Gong M, Zhang Q. et al. Metabolism and Regulation of Ascorbic Acid in Fruits. Plants (Basel) 2022; 11: 1602 DOI: 10.3390/plants11121602.
• 115 Carr AC, Vissers MC. Synthetic or food derived vitamin C are they equally bioavailable?. Nutrients 2013; 5: 4284-4304 DOI: 10.3390/nu5114284.
• 116 Hughes RL. A Review of the Role of the Gut Microbiome in Personalized Sports Nutrition. Front Nutr 2020; 6: 191 DOI: 10.3389/fnut.2019.00191.
• 117 Lee IM, Shiroma EJ, Lobelo F. et al. Lancet Physical Activity Series Working Group. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 2012; 380: 219-229 DOI: 10.1016/S0140-6736(12)61031-9.
• 118 Bento T, Mota MP, Vitorino A. et al. Age and Sex Differences in Physical Activity of Portuguese Adults and Older Adults. Healthcare (Basel) 2023; 11 (23) 3019 DOI: 10.3390/healthcare11233019.
• 119 Wang S, Lin J, Kuang L. et al. Risk factors for social isolation in older adults: A systematic review and meta-analysis. Public Health Nurs 2024; 41: 200-208 DOI: 10.1111/phn.13266.
• 120 Garrido A, Martínez de Toda I, Díaz Del Cerro E. et al. Social environment as a modulator of immunosenescence. Expert Rev Mol Med 2022; 24: e29 DOI: 10.1017/erm.2022.24.
• 121 Olszewska H, Kosny J, Jurowski P. et al. Physical activity of patients with a primary open angle glaucoma. Int J Ophthalmol 2020; 13: 1102-1108 DOI: 10.18240/ijo.2020.07.14.
• 122 Freitag CW, Behrens M, Menrad T. et al. Single- and Dual-Task Gait Performance in Patients With Open-Angle Glaucoma: A Cross-sectional Study. Transl Vis Sci Technol 2023; 12: 31 DOI: 10.1167/tvst.12.11.31.
• 123 Jeschke D, Zeilberger KH. Altern und körperliche Aktivität. Dtsch Arztebl 2004; 101 (12) A-789
• 124 Grosicki GJ, Langan SP, Bagley JR. et al. Gut check: Unveiling the influence of acute exercise on the gut microbiota. Exp Physiol 2023; 108: 1466-1480 DOI: 10.1113/EP091446.
• 125 Walsh EI, Smith L, Northey J. et al. Towards an understanding of the physical activity-BDNF-cognition triumvirate: A review of associations and dosage. Ageing Res Rev 2020; 60: 101044 DOI: 10.1016/j.arr.2020.101044.
• 126 Ciumărnean L, Milaciu MV, Negrean V. et al. Cardiovascular Risk Factors and Physical Activity for the Prevention of Cardiovascular Diseases in the Elderly. Int J Environ Res Public Health 2021; 19: 207 DOI: 10.3390/ijerph19010207.
• 127 Iso-Markku P, Kujala UM, Knittle K. et al. Physical activity as a protective factor for dementia and Alzheimerʼs disease: systematic review, meta-analysis and quality assessment of cohort and case-control studies. Br J Sports Med 2022; 56: 701-709 DOI: 10.1136/bjsports-2021-104981.
• 128 Wackerhage H, Sitzberger C, Kreuzpointner F. et al. WHO-Leitlinien zu körperlicher Aktivität und sitzendem Verhalten. Bayer Aztebl 2021; 3: 91-93
• 129 Hecht I, Achiron A, Man V. et al. Modifiable factors in the management of glaucoma: a systematic review of current evidence. Graefes Arch Clin Exp Ophthalmol 2017; 255: 789-796 DOI: 10.1007/s00417-016-3518-4.
• 130 Kawamura T, Muraoka I. Exercise-Induced Oxidative Stress and the Effects of Antioxidant Intake from a Physiological Viewpoint. Antioxidants (Basel) 2018; 7: 119 DOI: 10.3390/antiox7090119.
• 131 Rogers EM, Banks NF, Jenkins NDM. Acute effects of daily step count on postprandial metabolism and resting fat oxidation: a randomized controlled trial. J Appl Physiol (1985) 2023; 135: 812-822 DOI: 10.1152/japplphysiol.00052.2023.
• 132 Salthouse TA. Trajectories of normal cognitive aging. Psychol Aging 2019; 34: 17-24 DOI: 10.1037/pag0000288.
• 133 Shirolapov I, Zakharov A, Smirnova D. et al. Aging Brain, Dementia and Impaired Glymphatic Pathway: Causal Relationships. Psychiatr Danub 2023; 35 (Suppl. 2) 236-244
• 134 Cornell J, Salinas S, Huang HY. et al. Microglia regulation of synaptic plasticity and learning and memory. Neural Regen Res 2022; 17: 705-716 DOI: 10.4103/1673-5374.322423.
• 135 Badji A, Youwakim J, Cooper A. et al. Vascular cognitive impairment – Past, present, and future challenges. Ageing Res Rev 2023; 90: 102042 DOI: 10.1016/j.arr.2023.102042.
• 136 Arrigo A, Aragona E, Saladino A. et al. Cognitive Dysfunctions in Glaucoma: An Overview of Morpho-Functional Mechanisms and the Impact on Higher-Order Visual Function. Front Aging Neurosci 2021; 13: 747050 DOI: 10.3389/fnagi.2021.747050.
• 137 Freeman EE, Lesk MR, Harasymowycz P. et al. Maladaptive coping strategies and glaucoma progression. Medicine (Baltimore) 2016; 95: e4761 DOI: 10.1097/MD.0000000000004761.
• 138 Tan Z, Tung TH, Xu SQ. et al. Personality types of patients with glaucoma: A systematic review of observational studies. Medicine (Baltimore) 2021; 100: e25914 DOI: 10.1097/MD.0000000000025914.
• 139 Chen YY, Lai YJ, Wang JP. et al. The association between glaucoma and risk of depression: a nationwide population-based cohort study. BMC Ophthalmol 2018; 18: 146 DOI: 10.1186/s12886-018-0811-5.
• 140 Stolz C, Bulla A, Soch J. et al. Openness to Experience is associated with neural and performance measures of memory in older adults. Soc Cogn Affect Neurosci 2023; 18: nsad041 DOI: 10.1093/scan/nsad041.
• 141 Ferguson L, Sain D, Kürüm E. et al. One-year cognitive outcomes from a multiple real-world skill learning intervention with older adults. Aging Ment Health 2023; 27: 2134-2143 DOI: 10.1080/13607863.2023.2197847.
• 142 Leanos S, Kürüm E, Strickland-Hughes CM. et al. The Impact of Learning Multiple Real-World Skills on Cognitive Abilities and Functional Independence in Healthy Older Adults. J Gerontol B Psychol Sci Soc Sci 2023; 78: 1305-1317 DOI: 10.1093/geronb/gbad053.
• 143 Brydsten A, Rostila M, Dunlavy A. Social integration and mental health – a decomposition approach to mental health inequalities between the foreign-born and native-born in Sweden. Int J Equity Health 2019; 18: 48 DOI: 10.1186/s12939-019-0950-1.
• 144 Shatil E. Does combined cognitive training and physical activity training enhance cognitive abilities more than either alone? A four-condition randomized controlled trial among healthy older adults. Front Aging Neurosci 2013; 5: 8 DOI: 10.3389/fnagi.2013.00008.
• 145 European Glaucoma Society. Terminology and guidelines for glaucoma. 5th Edition. Savona: SvetPrint; 2021