Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations. The inaugural Norway-UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging.

Brain and Muscle Energy Group Institute of Oral Biology University of Oslo Oslo Norway

British Embassy Oslo Oslo Norway

Center for Healthy Aging Department of Neuroscience and Pharmacology Faculty of Health Sciences University of Copenhagen Copenhagen Denmark

Centre for Age Related Medicine Stavanger University Hospital Stavanger Norway

Centre for Molecular Medicine Norway University of Oslo Oslo Norway

Centre for Sustainable Healthcare Education Faculty of Medicine University of Oslo Oslo Norway

Department of Biochemistry University of Oxford Oxford UK

Department of Cellular and Molecular Medicine Center for Healthy Aging University of Copenhagen Copenhagen Denmark

Department of Clinical Medicine University of Bergen Bergen Norway

Department of Clinical Molecular Biology University of Oslo and Akershus University Hospital Lørenskog Norway

Department of Clinical Neuroscience University of Cambridge Cambridge UK

Department of Endocrinology Hematology and Gerontology Chiba University Graduate School of Medicine Chiba Japan

Department of Genetics Evolution and Environment Institute of Healthy Ageing University College London London UK

Department of Haematology Oslo University Hospital Oslo Norway

Department of Medical Genetics Cambridge Institute for Medical Research University of Cambridge Cambridge UK

Department of Microbiology and Immunology School of Medicine; Institute of Geriatric Immunology School of Medicine Jinan University Guangzhou China

Department of Microbiology Oslo University Hospital Oslo Norway

Department of Molecular Cell Biology Institute for Cancer Research Oslo University Hospital Montebello Oslo Norway

Department of Molecular Medicine Institute of Basic Medical Sciences University of Oslo Oslo Norway

Department of Neurobiology Care Sciences and Society Division of Neurogeriatrics Center for Alzheimer Research Karolinska Institutet Stockholm Sweden

Department of Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Neurology Akershus University Hospital Lørenskog Norway

Department of Neuroscience Erasmus MC Rotterdam The Netherlands

Department of Old Age Psychiatry Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Department of Physiology Medical School National and Kapodistrian University of Athens Athens Greece

Division of Anatomy Department of Molecular Medicine Institute of Basic Medical Sciences University of Oslo Oslo Norway

Guangdong Hong Kong Macau Great Bay Area Geroscience Joint Laboratory Guangzhou China

Institute for Molecular Medicine Finland HiLIFE University of Helsinki Helsinki Finland

Institute of Biosciences and Applications NCSR Demokritos Athens Greece

Institute of Clinical Medicine Campus Ahus University of Oslo Oslo Norway

Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway

Institute of Molecular Biology and Biotechnology Foundation for Research and Technology Heraklion Greece

International Clinical Research Centre St Anne's University Hospital Brno Czech Republic

Karolinska Institutet Stockholm Sweden

Laboratory of Molecular Gerontology National Institute on Aging National Institutes of Health Baltimore Maryland USA

Life and Health Sciences Research Institute School of Medicine University of Minho Campus de Gualtar Braga Portugal

Max Planck Institute for Biology of Ageing Cologne Germany

Medical School University of Crete Heraklion Greece

National Helenic Research Foundation Institute of Biology Medicinal Chemistry and Biotechnology Athens Greece

Netherlands Institute for Neuroscience Amsterdam The Netherlands

Norwegian National Centre for Ageing and Health Vestfold Hospital Trust Tønsberg Norway

Royal Norwegian Embassy in London London UK

School of Cardiovascular and Metabolic Medicine and Sciences Faculty of Life Sciences and Medicine King's College London London UK

The Norwegian Centre on Healthy Ageing Oslo Norway

Tracked bio Copenhagen Denmark

UK Dementia Research Institute University of Cambridge Cambridge UK

Xiangya School of Stomatology Central South University Changsha Hunan China

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WHO. Ageing and Health; 2022.

Fang EF, Xie C, Schenkel JA, et al. . A research agenda for ageing in China in the 21st century (2nd edition): focusing on basic and translational research, long-term care, policy and social networks. Ageing Res Rev. 2020;64:101174. 10.1016/j.arr.2020.101174 PubMed DOI PMC

Fang EF, Scheibye-Knudsen M, Jahn HJ, et al. . A research agenda for aging in China in the 21st century. Ageing Res Rev. 2015;24:197–205. 10.1016/j.arr.2015.08.003 PubMed DOI PMC

Woods T, Palmarini N, Corner L, et al. . Quantum healthy longevity for healthy people, planet, and growth. Lancet Healthy Longev. 2022;3:e811–e813. 10.1016/S2666-7568(22)00267-7 PubMed DOI

Livingston G, Huntley J, Sommerlad A, et al. . Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396:413–446. 10.1016/S0140-6736(20)30367-6 PubMed DOI PMC

Cox LS, Faragher RGA.. Linking interdisciplinary and multiscale approaches to improve healthspan—a new UK model for collaborative research networks in ageing biology and clinical translation. Lancet Healthy Longev. 2022;3:e318–e320. 10.1016/S2666-7568(22)00095-2 PubMed DOI

Regan JC, Khericha M, Dobson AJ, Bolukbasi E, Rattanavirotkul N, Partridge L.. Sex difference in pathology of the ageing gut mediates the greater response of female lifespan to dietary restriction. Elife. 2016;5:e10956. 10.7554/eLife.10956 PubMed DOI PMC

Regan JC, Lu YX, Urena E, et al. . Sexual identity of enterocytes regulates autophagy to determine intestinal health, lifespan and responses to rapamycin. Nat Aging. 2022;2:1145–1158. 10.1038/s43587-022-00308-7 PubMed DOI PMC

Juricic P, Lu YX, Leech T, et al. . Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy. Nat Aging. 2022;2:824–836. 10.1038/s43587-022-00278-w PubMed DOI PMC

Cox LS, Bellantuono I, Lord JM, et al. . Tackling immunosenescence to improve COVID-19 outcomes and vaccine response in older adults. Lancet Healthy Longev. 2020;1:e55–e57. 10.1016/S2666-7568(20)30011-8 PubMed DOI PMC

Camell CD, Yousefzadeh MJ, Zhu Y, et al. . Senolytics reduce coronavirus-related mortality in old mice. Science. 2021;373. 10.1126/science.abe4832 PubMed DOI PMC

Cox LS, Lord JM.. Targeting aging cells improves survival. Science. 2021;373:281–282. 10.1126/science.abi4474 PubMed DOI

Mannick JB, Del Giudice G, Lattanzi M, et al. . mTOR inhibition improves immune function in the elderly. Sci Transl Med. 2014;6:268ra179. 10.1126/scitranslmed.3009892 PubMed DOI

Mannick JB, Morris M, Hockey HP, et al. . TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med. 2018;10:eaaq1564. 10.1126/scitranslmed.aaq1564 PubMed DOI

Bischof E, Siow RC, Zhavoronkov A, Kaeberlein M.. The potential of rapalogs to enhance resilience against SARS-CoV-2 infection and reduce the severity of COVID-19. Lancet Healthy Longev. 2021;2:e105–e111. 10.1016/S2666-7568(20)30068-4 PubMed DOI PMC

Rolt A, Nair A, Cox LS.. Optimisation of a screening platform for determining IL-6 inflammatory signalling in the senescence-associated secretory phenotype (SASP). Biogerontology. 2019;20:359–371. 10.1007/s10522-019-09796-4 PubMed DOI PMC

Fang EF, Scheibye-Knudsen M, Chua KF, Mattson MP, Croteau DL, Bohr VA.. Nuclear DNA damage signalling to mitochondria in ageing. Nat Rev Mol Cell Biol. 2016;17:308–321. 10.1038/nrm.2016.14 PubMed DOI PMC

Kurki MI, Karjalainen J, Palta P, et al. ; FinnGen. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613:508–518. 10.1038/s41586-022-05473-8 PubMed DOI PMC

Fang EF, Scheibye-Knudsen M, Brace LE, et al. . Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell. 2014;157:882–896. 10.1016/j.cell.2014.03.026 PubMed DOI PMC

Fang EF, Lautrup S, Hou Y, et al. . NAD(+) in aging: molecular mechanisms and translational implications. Trends Mol Med. 2017;23:899–916. 10.1016/j.molmed.2017.08.001 PubMed DOI PMC

Fang EF, Hou Y, Palikaras K, et al. . Mitophagy inhibits amyloid-beta and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nat Neurosci. 2019;22:401–412. 10.1038/s41593-018-0332-9 PubMed DOI PMC

Wang H, Lautrup S, Caponio D, Zhang J, Fang EF.. DNA damage-induced neurodegeneration in accelerated ageing and Alzheimer’s disease. Int J Mol Sci. 2021;22:1–17. 10.3390/ijms22136748 PubMed DOI PMC

Fang EF, Kassahun H, Croteau DL, et al. . NAD(+) replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair. Cell Metab. 2016;24:566–581. 10.1016/j.cmet.2016.09.004 PubMed DOI PMC

Presterud R, Deng WH, Wennerstrom AB, et al. . Long-term nicotinamide riboside use improves coordination and eye movements in ataxia telangiectasia. Mov Disord. 2023. 10.1002/mds.29645 PubMed DOI

Aman Y, Schmauck-Medina T, Hansen M, et al. . Autophagy in healthy aging and disease. Nat Aging. 2021;1:634–650. 10.1038/s43587-021-00098-4 PubMed DOI PMC

Zhang J, Wang HL, Fang EF.. Autophagy and bioenergetics in aging. In: Fang EF, Bergersen LH, Gilmour BC, eds. Molecular, Cellular, and Metabolic Fundamentals of Human Aging. Elsevier Inc./Academic Press; 2022:107–119. eBook ISBN: 9780323916189

Fleming A, Bourdenx M, Fujimaki M, et al. . The different autophagy degradation pathways and neurodegeneration. Neuron. 2022;110:935–966. 10.1016/j.neuron.2022.01.017 PubMed DOI PMC

Schmauck-Medina T, Moliere A, Lautrup S, et al. . New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging (Albany NY). 2022;14:6829–6839. 10.18632/aging.204248 PubMed DOI PMC

Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G.. Hallmarks of aging: an expanding universe. Cell. 2023;186:243–278. 10.1016/j.cell.2022.11.001 PubMed DOI

Palikaras K, Lionaki E, Tavernarakis N.. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature. 2015;521:525–528. 10.1038/nature14300 PubMed DOI

Palikaras K, Lionaki E, Tavernarakis N.. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nat Cell Biol. 2018;20:1013–1022. 10.1038/s41556-018-0176-2 PubMed DOI

Wilson DM, 3rd, Cookson MR, Van Den Bosch L, Zetterberg H, Holtzman DM, Dewachter I.. Hallmarks of neurodegenerative diseases. Cell. 2023;186:693–714. 10.1016/j.cell.2022.12.032 PubMed DOI

Hou Y, Dan X, Babbar M, et al. . Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol. 2019;15:565–581. 10.1038/s41582-019-0244-7 PubMed DOI

Borbolis F, Palikaras K.. The compartmentalised nature of neuronal mitophagy: molecular insights and implications. Expert Rev Mol Med. 2022;24:e38. 10.1017/erm.2022.31 PubMed DOI PMC

Palikaras K, Tavernarakis N.. Regulation and roles of mitophagy at synapses. Mech Ageing Dev. 2020;187:111216. 10.1016/j.mad.2020.111216 PubMed DOI

Zaninello M, Palikaras K, Sotiriou A, Tavernarakis N, Scorrano L.. Sustained intracellular calcium rise mediates neuronal mitophagy in models of autosomal dominant optic atrophy. Cell Death Differ. 2022;29:167–177. 10.1038/s41418-021-00847-3 PubMed DOI PMC

Zaninello M, Palikaras K, Naon D, et al. . Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy. Nat Commun. 2020;11:4029. 10.1038/s41467-020-17821-1 PubMed DOI PMC

Princely Abudu Y, Pankiv S, Mathai BJ, et al. . NIPSNAP1 and NIPSNAP2 Act as “Eat Me” Signals for Mitophagy. Dev Cell. 2019;49:509–525.e12. 10.1016/j.devcel.2019.03.013 PubMed DOI

Lautrup S, Sinclair DA, Mattson MP, Fang EF.. NAD(+) in brain aging and neurodegenerative disorders. Cell Metab. 2019;30:630–655. 10.1016/j.cmet.2019.09.001 PubMed DOI PMC

Xie C, Zhuang XX, Niu Z, et al. . Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow. Nat Biomed Eng. 2022;6:76–93. 10.1038/s41551-021-00819-5 PubMed DOI PMC

Puri C, Gratian MJ, Rubinsztein DC.. Mammalian autophagosomes form from finger-like phagophores. Dev Cell. 2023;58:2746–2760.e5. 10.1016/j.devcel.2023.08.016 PubMed DOI

Festa BP, Siddiqi FH, Jimenez-Sanchez M, et al. . Microglial-to- neuronal CCR5 signaling regulates autophagy in neurodegeneration. Neuron. 2023;111:2021–2037.e12. 10.1016/j.neuron.2023.04.006 PubMed DOI

Papandreou ME, Konstantinidis G, Tavernarakis N.. Nucleophagy delays aging and preserves germline immortality. Nat Aging. 2023;3:34–46. 10.1038/s43587-022-00327-4 PubMed DOI PMC

Luo OJ, Lei W, Zhu G, et al. . Multidimensional single-cell analysis of human peripheral blood reveals characteristic features of the immune system landscape in aging and frailty. Nat Aging. 2022;2:348–364. 10.1038/s43587-022-00198-9 PubMed DOI

Xiao C, Ren Z, Zhang B, et al. . Insufficient epitope-specific T cell clones are responsible for impaired cellular immunity to inactivated SARS-CoV-2 vaccine in older adults. Nat Aging. 2023;3:418–435. 10.1038/s43587-023-00379-0 PubMed DOI PMC

Miller GW, Jones DP.. The nature of nurture: refining the definition of the exposome. Toxicol Sci. 2014;137:1–2. 10.1093/toxsci/kft251 PubMed DOI PMC

GjOra L, Strand BH, Bergh S, et al. . Current and future prevalence estimates of mild cognitive impairment, dementia, and its subtypes in a population-based sample of people 70 years and older in Norway: the HUNT Study. J Alzheimers Dis. 2021;79:1213–1226. 10.3233/JAD-201275 PubMed DOI PMC

Selbaek G, Stuebs J, Engedal K, et al. . Blood pressure trajectories over 35 years and dementia risk: a retrospective study: the HUNT Study. Front Aging Neurosci. 2022;14:931715. 10.3389/fnagi.2022.931715 PubMed DOI PMC

Naia L, Shimozawa M, Bereczki E, et al. . Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models. Mol Psychiatry. 2023;28:3966–3981. 10.1038/s41380-023-02289-4 PubMed DOI PMC

Watne LO, Pollmann CT, Neerland BE, et al. . Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip-fracture patients. J Clin Invest. 2023;133:e163472. 10.1172/JCI163472 PubMed DOI PMC

Sepulveda-Falla D, Barrera-Ocampo A, Hagel C, et al. . Familial Alzheimer’s disease-associated presenilin-1 alters cerebellar activity and calcium homeostasis. J Clin Invest. 2014;124:1552–1567. 10.1172/JCI66407 PubMed DOI PMC

Fang EF, Hou Y, Lautrup S, et al. . NAD(+) augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun. 2019;10:5284. 10.1038/s41467-019-13172-8 PubMed DOI PMC

Brelstaff J, Tolkovsky AM, Ghetti B, Goedert M, Spillantini MG.. Living neurons with tau filaments aberrantly expose phosphatidylserine and are phagocytosed by microglia. Cell Rep. 2018;24:1939–1948.e4. 10.1016/j.celrep.2018.07.072 PubMed DOI PMC

Brelstaff JH, Mason M, Katsinelos T, et al. . Microglia become hypofunctional and release metalloproteases and tau seeds when phagocytosing live neurons with P301S tau aggregates. Sci Adv. 2021;7:eabg4980. 10.1126/sciadv.abg4980 PubMed DOI PMC

Schweighauser M, Arseni D, Bacioglu M, et al. . Age-dependent formation of TMEM106B amyloid filaments in human brains. Nature. 2022;605:310–314. 10.1038/s41586-022-04650-z PubMed DOI PMC

Baggen J, Jacquemyn M, Persoons L, et al. . TMEM106B is a receptor mediating ACE2-independent SARS-CoV-2 cell entry. Cell. 2023;186:3427–3442.e22. 10.1016/j.cell.2023.06.005 PubMed DOI PMC

Guerreiro SR, Guimaraes MR, Silva JM, et al. . Chronic pain causes Tau-mediated hippocampal pathology and memory deficits. Mol Psychiatry. 2022;27:4385–4393. 10.1038/s41380-022-01707-3 PubMed DOI

Sotiropoulos I, Silva JM, Gomes P, Sousa N, Almeida OFX.. Stress and the etiopathogenesis of Alzheimer’s disease and depression. Adv Exp Med Biol. 2019;1184:241–257. 10.1007/978-981-32-9358-8_20 PubMed DOI

Silva JM, Rodrigues S, Sampaio-Marques B, et al. . Dysregulation of autophagy and stress granule-related proteins in stress-driven Tau pathology. Cell Death Differ. 2019;26:1411–1427. 10.1038/s41418-018-0217-1 PubMed DOI PMC

Gomes PA, Bodo C, Nogueras-Ortiz C, et al. . A novel isolation method for spontaneously released extracellular vesicles from brain tissue and its implications for stress-driven brain pathology. Cell Commun Signal. 2023;21:35. 10.1186/s12964-023-01045-z PubMed DOI PMC

Ezra M, Garbrecht J, Rasmussen N, et al. . The human pathome shows sex specific aging patterns post-development. BIoRxiv. 2023. 10.1101/2023.02.27.530179 DOI

Liang KX, Kristiansen CK, Mostafavi S, et al. . Disease-specific phenotypes in iPSC-derived neural stem cells with POLG mutations. EMBO Mol Med. 2020;12:e12146. 10.15252/emmm.202012146 PubMed DOI PMC

Hong Y, Kristiansen CK, Chen A, et al. . POLG genotype influences degree of mitochondrial dysfunction in iPSC derived neural progenitors, but not the parent iPSC or derived glia. Exp Neurol. 2023;365:114429. 10.1016/j.expneurol.2023.114429 PubMed DOI

Liang KX, Vatne GH, Kristiansen CK, et al. . N-acetylcysteine amide ameliorates mitochondrial dysfunction and reduces oxidative stress in hiPSC-derived dopaminergic neurons with POLG mutation. Exp Neurol. 2021;337:113536. 10.1016/j.expneurol.2020.113536 PubMed DOI

Norevik CS, Huuha AM, Rosbjorgen RN, et al. . Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer’s disease rat brain. J Sport Health Sci. 2023:S2095–2546(23)00072. 10.1016/j.jshs.2023.07.003 PubMed DOI

Cao SQ, Wang HL, Palikaras K, Tavernarakis N, Fang EF.. Chemotaxis assay for evaluation of memory-like behavior in wild-type and Alzheimer’s-disease-like C. elegans models. STAR Protoc. 2023;4:102250. 10.1016/j.xpro.2023.102250 PubMed DOI PMC

Mladenovic Djordjevic AN, Kapetanou M, Loncarevic-Vasiljkovic N, et al. . Pharmacological intervention in a transgenic mouse model improves Alzheimer’s-associated pathological phenotype: involvement of proteasome activation. Free Radic Biol Med. 2021;162:88–103. 10.1016/j.freeradbiomed.2020.11.038 PubMed DOI PMC

Abdelnour C, Gonzalez MC, Gibson LL, et al. . Dementia with Lewy bodies drug therapies in clinical trials: systematic review up to 2022. Neurol Ther. 2023;12:727–749. 10.1007/s40120-023-00467-8 PubMed DOI PMC