Jon Storm-Mathisen

• Belhaj, Imen; Åmellem, Ingrid; Tartanoglu, Can H.; Weidemann, Hanne Margrete; Vallenari, Evan Michael & Yang, Mingyi [Show all 10 contributors for this article] (2026). Lactate treatment improves brain biochemistry and cognitive function in transgenic Alzheimer’s and wild-type mice. Scientific Reports. 16(1). doi: 10.1038/s41598-026-48154-6. Full text in Research Archive Show summary

  Lactate, a well-known metabolite and signalling molecule, holds therapeutic potential for neurodegenerative diseases. Here, we investigated the effects of chronic lactate treatment on cognition and molecular biomarkers in the 5XFAD mouse model of Alzheimer’s disease (AD) and in wild-type (WT) controls using behavioural testing alongside proteomic and transcriptomic analyses. Mice received lactate or vehicle injections 4 days per week for 11 weeks, with behavioural testing before and after the treatment period. Lactate improved working memory in late-treated AD mice, without eliciting anxiety-like behaviour. At the molecular level, lactate reduced Il1b expression, and in a sex-dependent manner, normalised NEFL, and enhanced synaptic integrity proteins (OPCML, PPFIA2, STXBP3, SYT1, VGLUT2, VSNL1) in AD mice, while also augmenting mitochondrial regulators (ATP5G2, GRPEL1, SLC25A23) across genotypes. Notably, lactate upregulated low-abundance ionotropic glutamate receptor mRNAs (Grik3, Grin2c, Grid2ip) in female AD mice, indicating enhanced glutamatergic signalling. In WT mice, lactate increased expression of neurotrophic factors (Bdnf, Igf1, Vegfa), anti-inflammatory cytokines (Il4 and Il13), and the neuronal lactate transporter Mct2, suggesting promoted neuronal resilience. Together, these findings indicate that lactate treatment can mitigate cognitive decline and enhance molecular pathways of resilience in AD, warranting larger, age-stratified studies to validate its therapeutic potential and elucidate underlying mechanisms.

• Pan, Junping; Wang, Ping-Jie; Zhang, Jianying; Knapskog, Anne-Brita; Watne, Leiv Otto & Wang, He-Ling [Show all 40 contributors for this article] (2026). Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer’s disease pathology. Nature Aging. 6(5), p. 1079–1102. doi: 10.1038/s43587-026-01108-z. Full text in Research Archive
• Storm-Mathisen, Jon (2026). How Glutamate and GABA «Became» Neurotransmitters: Personal Account of a 65 Years’ Voyage. Journal of Neurochemistry. ISSN 0022-3042. 170(4). doi: 10.1111/jnc.70325. Full text in Research Archive
• Doncel, Beatriz Escobar; Papakosta, Anastasia; Storm-Mathisen, Jon & Fang, Evandro Fei (2026). Sea urchin bioactive compounds: emerging interventions for age-related diseases. Ageing Research Reviews. ISSN 1568-1637. 114, p. 102979–102979. doi: 10.1016/j.arr.2025.102979. Full text in Research Archive Show summary

  Among the marine bioresources, sea urchins are emerging as a promising provider of bioactive compounds with broad therapeutic potentials, including for ageing and age-related diseases. This review highlights the therapeutic promise of sea urchin bioactive compounds, covering evidence from both laboratory and clinical studies. Compounds found in sea urchin such as carotenoids, polyhydroxynaphthoquinones (PHNQs), and flavonoids demonstrate antioxidant and anti-inflammatory properties with notable cell viability improvements, targeting conditions like metabolic syndrome, cardiovascular disease, neurodegenerative disorders, as well as ophthalmic, dermatological, and post-menopausal conditions. Sea urchins hold great nutritional value, rich in proteins, minerals, and trace elements, which further supports their potential health benefits in humans. However, challenges remain, including the risk of adverse effects at high doses, limited bioavailability, species-specific bioactivities, and the limited understanding of their molecular mechanisms of action. Future research should focus on elucidating these mechanisms, as well as conducting rigorous preclinical and clinical investigations to validate their therapeutic efficacy. With continued research, we shall develop strategies for the best use of sea urchins including for health benefits.

• Ai, Ruixue; Mao, Lipeng; Jin, Xurui; Campos-Marques, Carlos; Zhang, Shi-qi & Pan, Junping [Show all 33 contributors for this article] (2025). NAD+ reverses Alzheimer’s neurological deficits via regulating differential alternative RNA splicing of EVA1C. Science Advances. 11(45). doi: 10.1126/sciadv.ady9811. Full text in Research Archive Show summary

  Dysfunctional alternative splicing events (ASEs) in RNA are markers of aging and Alzheimer’s disease (AD). As a key neuronal resilience metabolite, the oxidized nicotinamide adenine dinucleotide (NAD+) slows down AD progression in preclinical studies with several clinical trials ongoing. However, the underlying molecular mechanisms around how NAD+ enhances neuronal resilience, especially whether it has any effect on ASEs, have remained elusive. This study shows that NAD+ augmentation corrects the ASEs of many genes via a key protein, EVA1C (epithelial V-like antigen 1 homolog C), which is involved in neuronal development and activities. EVA1C is reduced in the hippocampus in patients with AD compared to cognitively normal ones. NAD+-induced memory retention is partially dependent on EVA1C, as adeno-associated virus–based Eva1c knockdown in the hippocampal CA1 region annuls NAD+-induced memory improvement in pathological Tau–bearing mice. We propose that NAD+ reduces AD pathologies, at least partially, via amplification of the NAD+-EVA1C splicing axis, pointing to a potential splice-switching therapy for AD.

• Pietilä, Riikka; Gaudio, Francesca Del; He, Liqun; Vázquez-Liébanas, Elisa; Vanlandewijck, Michael & Muhl, Lars [Show all 33 contributors for this article] (2023). Molecular anatomy of adult mouse leptomeninges. Neuron. ISSN 0896-6273. 111, p. 3745–3764. doi: 10.1016/j.neuron.2023.09.002. Full text in Research Archive Show summary

  Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.

• Raheel, Tayyaba Qureshi; Bjørkmo, Mona; Nordengen, Kaja; Gundersen, Vidar; Utheim, Tor Paaske & Watne, Leiv Otto [Show all 9 contributors for this article] (2020). Slc38a1 Conveys Astroglia-Derived Glutamine into GABAergic Interneurons for Neurotransmitter GABA Synthesis. Cells. 9(7), p. 1–12. doi: 10.3390/cells9071686. Full text in Research Archive Show summary

  GABA signaling is involved in a wide range of neuronal functions, such as synchronization of action potential firing, synaptic plasticity and neuronal development. Sustained GABA signaling requires efficient mechanisms for the replenishment of the neurotransmitter pool of GABA. The prevailing theory is that exocytotically released GABA may be transported into perisynaptic astroglia and converted to glutamine, which is then shuttled back to the neurons for resynthesis of GABA—i.e., the glutamate/GABA-glutamine (GGG) cycle. However, an unequivocal demonstration of astroglia-to-nerve terminal transport of glutamine and the contribution of astroglia-derived glutamine to neurotransmitter GABA synthesis is lacking. By genetic inactivation of the amino acid transporter Solute carrier 38 member a1 (Slc38a1)—which is enriched on parvalbumin+ GABAergic neurons—and by intraperitoneal injection of radiolabeled acetate (which is metabolized to glutamine in astroglial cells), we show that Slc38a1 mediates import of astroglia-derived glutamine into GABAergic neurons for synthesis of GABA. In brain slices, we demonstrate the role of Slc38a1 for the uptake of glutamine specifically into GABAergic nerve terminals for the synthesis of GABA depending on demand and glutamine supply. Thus, while leaving room for other pathways, our study demonstrates a key role of Slc38a1 for newly formed GABA, in harmony with the existence of a GGG cycle.

• Aman, Yahyah; Frank, Johannes; Lautrup, Sofie Hindkjær; Matysek, Adrian; Niu, Zhangming & Yang, Guang [Show all 13 contributors for this article] (2020). The NAD+-mitophagy axis in healthy longevity and in artificial intelligence-based clinical applications. Mechanisms of Ageing and Development. ISSN 0047-6374. 185, p. 1–11. doi: 10.1016/j.mad.2019.111194. Full text in Research Archive Show summary

  Nicotinamide adenine dinucleotide (NAD+) is an important natural molecule involved in fundamental biological processes, including the TCA cycle, OXPHOS, β-oxidation, and is a co-factor for proteins promoting healthy longevity. NAD+ depletion is associated with the hallmarks of ageing and may contribute to a wide range of age-related diseases including metabolic disorders, cancer, and neurodegenerative diseases. One of the central pathways by which NAD+ promotes healthy ageing is through regulation of mitochondrial homeostasis via mitochondrial biogenesis and the clearance of damaged mitochondria via mitophagy. Here, we highlight the contribution of the NAD+-mitophagy axis to ageing and age-related diseases, and evaluate how boosting NAD+ levels may emerge as a promising therapeutic strategy to counter ageing as well as neurodegenerative diseases including Alzheimer’s disease. The potential use of artificial intelligence to understand the roles and molecular mechanisms of the NAD+-mitophagy axis in ageing is discussed, including possible applications in drug target identification and validation, compound screening and lead compound discovery, biomarker development, as well as efficacy and safety assessment. Advances in our understanding of the molecular and cellular roles of NAD+ in mitophagy will lead to novel approaches for facilitating healthy mitochondrial homoeostasis that may serve as a promising therapeutic strategy to counter ageing-associated pathologies and/or accelerated ageing.

View all works in NVA

• Blackstad, Jan Sigurd Beddari; Osen, Kirsten; Storm-Mathisen, Jon & Leergaard, Trygve Brauns (2025). The Evolutionary Reorganization of the Dentate Gyrus and CA3 in an Ontogenetic Perspective. Full text in Research Archive
• Wang, Heling; Siow, Richard; Schmauck-Medina, Tomás Alejandro; Zhang, Jianying; Sandset, Per Morten & Filshie, Clare [Show all 38 contributors for this article] (2024). Meeting Summary of The NYO3 5th NO-Age/AD Meeting and the 1st Norway-UK Joint Meeting on Aging and Dementia: Recent Progress on the Mechanisms and Interventional Strategies. The journals of gerontology. Series A, Biological sciences and medical sciences. ISSN 1079-5006. 79(4), p. 1–10. doi: 10.1093/gerona/glae029. Full text in Research Archive Show summary

  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.

View all works in NVA