Jianying Zhang

• Wang, He-Ling; Zhang, Jianying & Fang, Evandro Fei (2026). NAD+ augmentation in brain aging: hype, hope, or emerging reality? Trends in endocrinology and metabolism. ISSN 1043-2760. doi: 10.1016/j.tem.2026.09.003. Fulltekst i vitenarkiv
• Ling, Zhipeng; Pan, Jun-Ping; Xiao, Xianglu; Wu, Wenfan; Chen, Guisi & Shi, Fang [Vis alle 27 forfattere av denne artikkelen] (2026). AI-assisted discovery of an ABCA1/ABCG1 activator for restoring mitophagy and mitigating Alzheimer’s pathology. Molecular Neurodegeneration. doi: 10.1186/s13024-026-00998-2. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Defective mitophagy is a key pathological risk of Alzheimer’s disease (AD), yet available pharmacological agents capable of restoring mitophagy remain clinically limited, largely due to the lack of tools for drug screening and target identification. To address this, we introduce an integrated platform with three novel artificial intelligence (AI)-enabled approaches—the phenotype-based screening model ‘CellAutoFM’, the drug-likeness predictor ‘ADMET Ranker’, and the target deconvolution method ‘PROCAT’. Using this platform together with wet lab validation, Crassifolin A (JGX-1) is identified as a potent natural product-derived mitophagy inducer; structurally, JGX-1 directly binds to ATP-binding cassette sub-family A member 1 (ABCA1) and sub-family G member 1 (ABCG1), triggering enhanced cholesterol efflux which activates PINK1/Parkin-dependent mitophagy. In both in vitro and in vivo AD laboratory models, JGX-1 reduces amyloid-β and Tau pathologies in an autophagy/mitophagy-dependent manner as these benefits are dramatically blunted with key mitophagy genes knocked down. Collectively, we provide an open-access, reproducible AI-assisted platform for rapid compound screening, drug-likeness evaluation, and potential target prediction to advance drug discovery. Through this paradigm, we unveil modulating the ABCA1/ABCG1-mediated cholesterol-mitophagy pathway as a promising anti-AD strategy, with a novel drug candidate JGX-1 identified.

• Pan, Junping; Zhang, Jianying; Wang, Ping Jie; Chen, Guobing & Fang-Stavem, Fei (2026). Mitophagy mitigates tau acetylation via the ULK1-NAD⁺/SIRT1 axis in Alzheimer’s disease. Autophagy. ISSN 1554-8627. doi: 10.1080/15548627.2026.2689031. Fulltekst i vitenarkiv
• Suaste, Veronica; Presterud, Rebecca; Wennerström, Anna Berit; Wang, Heling; Zhang, Jianying & Lund, Solveig Osnes [Vis alle 16 forfattere av denne artikkelen] (2026). Transcriptional Profiling Shows Dampening of Interferon Gene Signatures by NAD Augmentation in Ataxia-Telangiectasia. International Journal of Molecular Sciences. ISSN 1661-6596. 27(13). doi: 10.3390/ijms27135652. Fulltekst i vitenarkiv Vis sammendrag

  Ataxia-Telangiectasia (A-T) is a multisystem disorder caused by loss of A-T mutated (ATM) protein activity, characterized clinically by immunodeficiency and cerebellar ataxia. ATM is a master regulator of DNA damage responses and loss of ATM function is accompanied by persistent activation of PARP1 leading to depletion of intracellular NAD+ and dysfunction of a series of cellular signalling pathways dependent on NAD+, providing a mechanistic rationale for NAD+ augmentation therapy. We performed a clinical trial of NAD+ augmentation with nicotinamide riboside (NR) over 24 months in A-T patients where we observed improved coordination and eye movements in A-T patients. Here, by using peripheral blood mononuclear cells, we performed longitudinal transcriptome profiling to define molecular signatures of A-T and to assess pathway-level responses to NR supplementation. A-T patients exhibited reproducible transcriptomic alterations involving immune, vascular, and inflammatory pathways. NAD+ augmentation was associated with suppression of interferon response genes and modulation of networks correlated with neurological improvement. These findings establish systemic molecular signatures of A-T and identify potential blood-based biomarkers that reflect disease processes and therapeutic response, supporting the use of NAD+ augmentation as a disease-modifying strategy in A-T by dampening interferon signalling.

• Pan, Junping; Wang, Ping-Jie; Zhang, Jianying; Knapskog, Anne-Brita; Watne, Leiv Otto & Wang, He-Ling [Vis alle 40 forfattere av denne artikkelen] (2026). Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer’s disease pathology. Nature Aging. 6(5), s. 1079–1102. doi: 10.1038/s43587-026-01108-z. Fulltekst i vitenarkiv
• Fang-Stavem, Fei; Fang, Yuan; Chen, Guobing; Wang, He-Ling; Zhang, Jianying & Wu, Chenkai [Vis alle 36 forfattere av denne artikkelen] (2025). Adapting health, economic and social policies to address population aging in China. Nature Aging. 5, s. 2176–2187. doi: 10.1038/s43587-025-00999-8. Fulltekst i vitenarkiv Vis sammendrag

  Despite its rapid economic rise over the past four decades, China now grapples with the challenge of accommodating and supporting its expanding aging population. In 2020, 18% of its population were over age 60, and 2.5% were over age 80, projected to rise to 39% and 10%, respectively, by 2050. This demographic shift places China at the forefront of diverse individual, familial and societal challenges. Here, we review these challenges in the context of emerging breakthroughs in basic and translational research, shifts in healthcare paradigms, evolving socioeconomic and political dynamics, and policy innovations. We synthesize China’s current policies toward promoting healthy longevity in the general population, focusing on social health insurance, long-term care insurance, community and home-based care and palliative care, as well as gerontological research, public health prevention, nutritional and medical interventions, while identifying strengths and gaps. Finally, we propose suggestions to promote a more inclusive, resilient and happier aging society within China’s distinctive sociopolitical and cultural context. China’s dramatic demographic shift toward population aging raises challenges at the individual, familial and societal levels. Fang et al. review these challenges and emerging policies designed to promote healthy longevity in China.

• Zhang, Jianying; Wang, Heling; Lautrup, Sofie Hindkjær; Nilsen, Hilde; Treebak, Jonas T. & Watne, Leiv Otto [Vis alle 28 forfattere av denne artikkelen] (2025). Emerging strategies, applications and challenges of targeting NAD+ in the clinic. Nature Aging. 5(9), s. 1704–1731. doi: 10.1038/s43587-025-00947-6. Fulltekst i vitenarkiv Vis sammendrag

  Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD+-related clinical trials, focusing on aging and neurodegenerative diseases. We discuss the established NAD+ precursors nicotinic acid and nicotinamide, newer compounds such as nicotinamide riboside and nicotinamide mononucleotide, and emerging precursors. We also discuss technological advances including in industrial-scale production and real-time detection, which are facilitating NAD+ research and clinical translation. Finally, we emphasize the need for further large-scale studies to determine optimal dose, administration routes and frequency, as well as long-term safety and interindividual variability in response.

• Wang, Heling; Duque, Gustavo; Siow, Richard; Medina, Tomás Alejandro Schmauck; Zhang, Jianying & Sandset, Per Morten [Vis alle 39 forfattere av denne artikkelen] (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). doi: 10.1093/gerona/glae029. Fulltekst i vitenarkiv Vis sammendrag

  Abstract 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.

• Wang, Heling; Zhang, Jianying; Cao, Shuqin; Lagartos, Maria Jose Donate; Zhang, Shi-qi & Lautrup, Sofie Hindkjær [Vis alle 10 forfattere av denne artikkelen] (2024). A luminescent-based protocol for NAD+/NADH detection in C. elegans, mice, and human whole blood. STAR Protocols. 5(4). doi: 10.1016/j.xpro.2024.103428. Fulltekst i vitenarkiv Vis sammendrag

  Here, we present a NAD+/NADH detection assay for evaluating NAD+, NADH, and NAD+/NADH ratio across diverse biological models, including Caenorhabditis elegans, mouse muscle tissue, mouse whole blood, and human whole blood. We describe steps for sample collection and preparation from different models as well as detection and calculation of NAD+ and NADH levels. This protocol is applicable for quantifying cellular/tissue NAD+ and NADH levels across different biological models.

• Veverová, Kateřina; Laczó, Jan; Katonová, Alžběta; Horáková, Hana; Matušková, Veronika & Angelucci, Francesco [Vis alle 14 forfattere av denne artikkelen] (2024). Alterations of human CSF and serum-based mitophagy biomarkers in the continuum of Alzheimer disease. Autophagy. ISSN 1554-8627. 20(8), s. 1868–1878. doi: 10.1080/15548627.2024.2340408. Fulltekst i vitenarkiv Vis sammendrag

  Defective mitophagy is consistently found in postmortem brain and iPSC-derived neurons from Alzheimer disease (AD) patients. However, there is a lack of extensive examination of mitophagy status in serum or cerebrospinal fluid (CSF), and the clinical potential of mitophagy biomarkers has not been tested. We quantified biomarkers of mitophagy/autophagy and lysosomal degradation (PINK1, BNIP3L and TFEB) in CSF and serum from 246 individuals, covering mild cognitive impairment due to AD (MCI-AD, n = 100), dementia due to AD (AD-dementia, n = 100), and cognitively unimpaired individuals (CU, n = 46), recruited from the Czech Brain Aging Study. Cognitive function and brain atrophy were also assessed. Our data show that serum and CSF PINK1 and serum BNIP3L were higher, and serum TFEB was lower in individuals with AD than in corresponding CU individuals. Additionally, the magnitude of mitophagy impairment correlated with the severity of clinical indicators in AD patients. Specifically, levels of PINK1 positively correlated with phosphorylated (p)-MAPT/tau (181), total (t)-MAPT/tau, NEFL (neurofilament light chain), and NRGN (neurogranin) levels in CSF and negatively with memory, executive function, and language domain. Serum TFEB levels negatively correlated with NEFL and positively with executive function and language. This study reveals mitophagy impairment reflected in biofluid biomarkers of individuals with AD and associated with more advanced AD pathology.

• Quan, Xu; Xin, Ying; Wang, Heling; Sun, Yingjie; Chen, Chanchan & Zhang, Jianying (2023). Implications of altered sirtuins in metabolic regulation and oral cancer. PeerJ. 11. doi: 10.7717/peerj.14752. Fulltekst i vitenarkiv Vis sammendrag

  Sirtuins (SIRTs 1-7) are a group of histone deacetylase enzymes with a wide range of enzyme activities that target a range of cellular proteins in the nucleus, cytoplasm, and mitochondria for posttranslational modifications by acetylation (SIRT1, 2, 3, and 5) or ADP ribosylation (SIRT4, 6, and 7). A variety of cellular functions, including mitochondrial functions and functions in energy homeostasis, metabolism, cancer, longevity and ageing, are regulated by sirtuins. Compromised sirtuin functions and/or alterations in the expression levels of sirtuins may lead to several pathological conditions and contribute significantly to alterations in metabolic phenotypes as well as oral carcinogenesis. Here, we describe the basic characteristics of seven mammalian sirtuins. This review also emphasizes the key molecular mechanisms of sirtuins in metabolic regulation and discusses the possible relationships of sirtuins with oral cancers. This review will provide novel insight into new therapeutic approaches targeting sirtuins that may potentially lead to effective strategies for combating oral malignancies.

• Xie, Chenglong; Zhuang, Xu-Xu; Niu, Zhangming; Ai, Ruixue; Lautrup, Sofie Hindkjær & Zheng, Shuangjia [Vis alle 29 forfattere av denne artikkelen] (2022). Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow. Nature Biomedical Engineering. 6(1), s. 76–93. doi: 10.1038/s41551-021-00819-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract A reduced removal of dysfunctional mitochondria is common to aging and age-related neurodegenerative pathologies such as Alzheimer’s disease (AD). Strategies for treating such impaired mitophagy would benefit from the identification of mitophagy modulators. Here we report the combined use of unsupervised machine learning (involving vector representations of molecular structures, pharmacophore fingerprinting and conformer fingerprinting) and a cross-species approach for the screening and experimental validation of new mitophagy-inducing compounds. From a library of naturally occurring compounds, the workflow allowed us to identify 18 small molecules, and among them two potent mitophagy inducers (Kaempferol and Rhapontigenin). In nematode and rodent models of AD, we show that both mitophagy inducers increased the survival and functionality of glutamatergic and cholinergic neurons, abrogated amyloid-β and tau pathologies, and improved the animals’ memory. Our findings suggest the existence of a conserved mechanism of memory loss across the AD models, this mechanism being mediated by defective mitophagy. The computational–experimental screening and validation workflow might help uncover potent mitophagy modulators that stimulate neuronal health and brain homeostasis.

• Wang, Heling; Lautrup, Sofie Hindkjær; Caponio, Domenica; Zhang, Jianying & Fang, Fei (2021). Dna damage‐induced neurodegeneration in accelerated ageing and alzheimer’s disease. International Journal of Molecular Sciences. ISSN 1661-6596. 22(13), s. 1–17. doi: 10.3390/ijms22136748. Fulltekst i vitenarkiv Vis sammendrag

  DNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of XPA), Cockayne syndrome group A and group B (CSA, CSB, and are caused by mutations of CSA and CSB, respectively), ataxia-telangiectasia (A-T, caused by mutation of ATM), and Werner syndrome (WS, with most cases caused by mutations in WRN). Except for WS, a common trait of the aforementioned progerias is neurodegeneration. Evidence from studies using animal models and patient tissues suggests that the associated DNA repair deficiencies lead to depletion of cellular nicotinamide adenine dinucleotide (NAD+), resulting in impaired mitophagy, accumulation of damaged mitochondria, metabolic derailment, energy deprivation, and finally leading to neuronal dysfunction and loss. Intriguingly, these features are also observed in Alzheimer’s disease (AD), the most common type of dementia affecting more than 50 million individuals worldwide. Further studies on the mechanisms of the DNA repair deficient premature ageing diseases will help to unveil the mystery of ageing and may provide novel therapeutic strategies for AD.

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• Wang, Heling; Siow, Richard; Schmauck-Medina, Tomás Alejandro; Zhang, Jianying; Sandset, Per Morten & Filshie, Clare [Vis alle 38 forfattere av denne artikkelen] (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), s. 1–10. doi: 10.1093/gerona/glae029. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Zhang, Jianying; Wang, Heling; Veverová, Kateřina; Vyhnálek, Martin & Fang, Fei (2024). Identification and potential clinical applications of novel autophagy/mitophagy proteins in the biofluids of Alzheimer's disease patients. Ageing Research Reviews. ISSN 1568-1637. 99. doi: 10.1016/j.arr.2024.102378. Fulltekst i vitenarkiv Vis sammendrag

  Highlights Elevated PINK1 and reduced TFEB in CSF and serum samples of AD patients. Correlations were found between levels of PINK1, TFEB, and clinical indicators of AD. Changes of the fluid protein levels of mitophagy/autophagy proteins could be developed into markers in assisting diagnsosi and prognosis.

• Schmauck-Medina, Tomás Alejandro; Molière, Adrian; Lautrup, Sofie Hindkjær; Zhang, Jianying; Chlopicki, Stefan & Madsen, Helena Borland [Vis alle 21 forfattere av denne artikkelen] (2022). New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging. 14(16), s. 6829–6839. doi: 10.18632/aging.204248. Fulltekst i vitenarkiv Vis sammendrag

  Genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, loss of proteostasis, deregulated nutrient-sensing, cellular senescence, stem cell exhaustion, and altered intercellular communication were the original nine hallmarks of ageing proposed by López-Otín and colleagues in 2013. The proposal of these hallmarks of ageing has been instrumental in guiding and pushing forward research on the biology of ageing. In the nearly past 10 years, our in-depth exploration on ageing research has enabled us to formulate new hallmarks of ageing which are compromised autophagy, microbiome disturbance, altered mechanical properties, splicing dysregulation, and inflammation, among other emerging ones. Amalgamation of the ‘old’ and ‘new’ hallmarks of ageing may provide a more comprehensive explanation of ageing and age-related diseases, shedding light on interventional and therapeutic studies to achieve healthy, happy, and productive lives in the elderly.

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