NAD + Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair
Open accessAbstract
Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD+, and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD+ reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan in both animal models. Mechanistically, treatments that increase intracellular NAD+ also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial dysfunction through nuclear DNA damage-induced nuclear-mitochondrial signaling, and demonstrates that they are important pathophysiological determinants in premature aging of A-T, pointing to therapeutic interventions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NAD+ supplementation mitigates premature aging phenotypes associated with defects in DNA repair by restoring mitochondrial function and mitophagy.
“Indeed, NAD+ supplementation mitigates premature aging phenotypes associated with defects in DNA repair by restoring mitochondrial function and mitophagy (72, 73).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [73]
NAD+ depletion is reported in several models of accelerated ageing that exhibit neurodegeneration, as well as in neurodegenerative diseases including Alzheimer disease, Parkinson disease and amyotrophic lateral sclerosis.
“NAD+ depletion is reported in several models of accelerated ageing which exhibit neurodegeneration33,134,135, as well as in neuro-degenerative diseases, including Alzheimer disease136, Parkinson disease137,138 and amyotrophic lateral sclerosis (ALS)139.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [135]
NAD+ replenishment using NR and/or NMN delays progeroid phenotype and extends lifespan in C. elegans models of xeroderma pigmentosum group A, ataxia telangiectasia and Cockayne syndrome, and in a worm model of Werner syndrome.
“NAD+ replenishment, using NR and/or NMN, has also been effective in delaying progeroid phenotype and extending lifespan in relevant C. elegans models of xeroderma pigmentosum group A, ataxia telangiectasia and Cockayne syndrome33,134,135 and in a worm model of Werner syndrome (a progeroid disease)196.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [135]
NMN treatment significantly increased NAD+ levels and maximum lifespan in a mouse model of ataxia telangiectasia.
“NMN treatment significantly increased NAD+ levels and the maximum lifespan also in a mouse model of ataxia telangiectasia135.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [135]
In wild-type yeast and C. elegans, low micromolar concentrations of NR extend lifespan in a sirtuin-dependent manner.
“In both wild-type yeast and C. elegans, low (micromolar) concentrations of NR extend lifespan in a sirtuin-dependent manner135,189,190.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [135]
In C. elegans, PARP inhibition results in significant lifespan extension in wild-type worms, in a model of ataxia telangiectasia and under hyperglycaemic conditions.
“In C. elegans, PARP inhibition results in a significant lifespan extension in wild-type worms190, in a model of ataxia telangiectasia135 and under hyperglycaemic conditions221.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [135]
Atm−/− mice show mitochondrial defects, and NAD+ supplementation lessens their health deterioration.
“Similarly, Atm−/− mice also have mitochondrial defects and interventions based on NAD+ supplementation88 attenuate their health decline.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [88]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466 · see citing works
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739 · see citing works
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer
Mateo, J., Carreira, S., Sandhu, S., Miranda, S., Mossop, H., Perez-Lopez, R., Nava Rodrigues, D., Robinson, D., Omlin, A., Tunariu, N., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1506859 · Cited by 2,185 · see citing works
Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase
Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., Howitz, K. T., Gorospe, M., de Cabo, R., & Sinclair, D. A. (2004) · Science · doi:10.1126/science.1099196 · Cited by 1,924 · see citing works
Self-citationThe ATM protein kinase: regulating the cellular response to genotoxic stress, and more
Shiloh, Y., & Ziv, Y. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3546 · Cited by 1,649 · see citing works
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648 · see citing works
Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia
Barlow, C., Hirotsune, S., Paylor, R. E., Liyanage, M., Eckhaus, M., Collins, F. S., Shiloh, Y., Crawley, J. N., Ried, T., Tagle, D. A., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80086-0 · Cited by 1,450 · see citing works
NAD <sup>+</sup> in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319 · see citing works
Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D’Amico, D., Ropelle, E. R., Lutolf, M. P., Aebersold, R., et al. (2016) · Science · doi:10.1126/science.aaf2693 · Cited by 1,255 · cited 2× · see citing works
“NAD+ is a key cellular factor linked to metabolism, MT health, stem cell rejuvenation, neuroprotection, and longevity in worms and mice (Igarashi and Guarente, 2016; Verdin, 2015; Zhang et al., 2016).”
Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage
Falck, J., Coates, J., & Jackson, S. P. (2005) · Nature · doi:10.1038/nature03442 · Cited by 1,248 · see citing works
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.022 · Cited by 1,238 · see citing works
Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y.-S., Viswanathan, M., Schoonjans, K., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.016 · Cited by 1,210 · see citing works
Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Matsuoka, S., Takubo, K., Hamaguchi, I., Nomiyama, K., Hosokawa, K., Sakurada, K., Nakagata, N., et al. (2004) · Nature · doi:10.1038/nature02989 · Cited by 1,175 · cited 2× · see citing works
“Defects in DNA repair can be associated with mitochondrial (MT) dysfunction, neuropathy, and ataxia, as reported in ATM (Guo et al., 2010; Ito et al., 2004; Valentin-Vega et al., 2012), Xeroderma pigmentosum complementation group A (XPA), and Cockayne syndrome group B (CSB) (Fang et al., 2014;…”
ATM Activation by Oxidative Stress
Guo, Z., Kozlov, S., Lavin, M. F., Person, M. D., & Paull, T. T. (2010) · Science · doi:10.1126/science.1192912 · Cited by 1,079 · see citing works
A novel pathway regulates memory and plasticity via SIRT1 and miR-134
Gao, J., Wang, W.-Y., Mao, Y.-W., Gräff, J., Guan, J.-S., Pan, L., Mak, G., Kim, D., Su, S. C., & Tsai, L.-H. (2010) · Nature · doi:10.1038/nature09271 · Cited by 975 · see citing works
SIRT6 Promotes DNA Repair Under Stress by Activating PARP1
Mao, Z., Hine, C., Tian, X., Van Meter, M., Au, M., Vaidya, A., Seluanov, A., & Gorbunova, V. (2011) · Science · doi:10.1126/science.1202723 · Cited by 867 · see citing works
Compromised autophagy and neurodegenerative diseases
Menzies, F. M., Fleming, A., & Rubinsztein, D. C. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3961 · Cited by 851 · see citing works
Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans
Palikaras, K., Lionaki, E., & Tavernarakis, N. (2015) · Nature · doi:10.1038/nature14300 · Cited by 770 · see citing works
Bieganowski, P., & Brenner, C. (2004) · Cell · doi:10.1016/s0092-8674(04)00416-7 · Cited by 750 · see citing works
Defective Mitophagy in XPA via PARP-1 Hyperactivation and NAD+/SIRT1 Reduction
Fang, E. F., Scheibye-Knudsen, M., Brace, L. E., Kassahun, H., SenGupta, T., Nilsen, H., Mitchell, J. R., Croteau, D. L., & Bohr, V. A. (2014) · Cell · doi:10.1016/j.cell.2014.03.026 · Cited by 711 · see citing works
Self-citationSun, N., Yun, J., Liu, J., Malide, D. A., Liu, C., Rovira, I. I., Holmström, K. M., Fergusson, M. M., Yoo, Y. H., Combs, C. A., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.009 · Cited by 696 · see citing works
Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators
Hubbard, B. P., Gomes, A. P., Dai, H., Li, J., Case, A. W., Considine, T., Riera, T. V., Lee, J. E., Yen, E. S., Lamming, D. W., et al. (2013) · Science · doi:10.1126/science.1231097 · Cited by 618 · see citing works
Self-citationAcetylation of the C Terminus of Ku70 by CBP and PCAF Controls Bax-Mediated Apoptosis
Cohen, H. Y., Lavu, S., Bitterman, K. J., Hekking, B., Imahiyerobo, T. A., Miller, C. M., Frye, R. A., Ploegh, H. L., Kessler, B. M., & Sinclair, D. A. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00094-2 · Cited by 574 · see citing works
Self-citationThe multifaceted functions of sirtuins in cancer
Chalkiadaki, A., & Guarente, L. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3985 · Cited by 501 · see citing works
Paull, T. T. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034335 · Cited by 458 · see citing works
C. elegans SIR-2.1 Interacts with 14-3-3 Proteins to Activate DAF-16 and Extend Life Span
Berdichevsky, A., Viswanathan, M., Horvitz, H. R., & Guarente, L. (2006) · Cell · doi:10.1016/j.cell.2006.04.036 · Cited by 393 · see citing works
Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB
Mair, W., Morantte, I., Rodrigues, A. P. C., Manning, G., Montminy, M., Shaw, R. J., & Dillin, A. (2011) · Nature · doi:10.1038/nature09706 · Cited by 393 · see citing works
Nuclear DNA damage signalling to mitochondria in ageing
Fang, E. F., Scheibye-Knudsen, M., Chua, K. F., Mattson, M. P., Croteau, D. L., & Bohr, V. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.14 · Cited by 387 · see citing works
Self-citationCheng, A., Yang, Y., Zhou, Y., Maharana, C., Lu, D., Peng, W., Liu, Y., Wan, R., Marosi, K., Misiak, M., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.10.013 · Cited by 371 · see citing works
Self-citationMitochondrial dysfunction in ataxia-telangiectasia
Valentin-Vega, Y. A., MacLean, K. H., Tait-Mulder, J., Milasta, S., Steeves, M., Dorsey, F. C., Cleveland, J. L., Green, D. R., & Kastan, M. B. (2012) · Blood · doi:10.1182/blood-2011-08-373639 · Cited by 365 · see citing works
A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in Cockayne syndrome
Scheibye-Knudsen, M., Mitchell, S. J., Fang, E. F., Iyama, T., Ward, T., Wang, J., Dunn, C. A., Singh, N., Veith, S., Hasan-Olive, M. M., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.005 · Cited by 352 · see citing works
Self-citationChen, B. P. C., Chan, D. W., Kobayashi, J., Burma, S., Asaithamby, A., Morotomi‐Yano, K., Botvinick, E. L., Qin, J., & Chen, D. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408827200 · Cited by 320 · see citing works
SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair
McCord, R. A., Michishita, E., Hong, T., Berber, E., Boxer, L. D., Kusumoto, R., Guan, S., Shi, X., Gozani, O., Burlingame, A. L., et al. (2009) · Aging · doi:10.18632/aging.100011 · Cited by 313 · see citing works
Self-citationmTORC1 and SIRT1 Cooperate to Foster Expansion of Gut Adult Stem Cells during Calorie Restriction
Igarashi, M., & Guarente, L. (2016) · Cell · doi:10.1016/j.cell.2016.05.044 · Cited by 302 · see citing works
Kauffman, A., Ashraf, J. M., Corces, M. R., Landis, J. N., & Murphy, C. T. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000372 · Cited by 284 · see citing works
SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons
Dobbin, M. M., Madabhushi, R., Pan, L., Chen, Y., Kim, D., Gao, J., Ahanonu, B., Pao, P.-C., Qiu, Y., Zhao, Y., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3460 · Cited by 250 · see citing works
Maintaining genome stability in the nervous system
McKinnon, P. J. (2013) · Nature Neuroscience · doi:10.1038/nn.3537 · Cited by 229 · see citing works
Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia
Li, J., Chen, J., Ricupero, C. L., Hart, R. P., Schwartz, M. S., Kusnecov, A., & Herrup, K. (2012) · Nature Medicine · doi:10.1038/nm.2709 · Cited by 210 · see citing works
Self-citationCurrent and potential therapeutic strategies for the treatment of ataxia-telangiectasia
Lavin, M. F., Gueven, N., Bottle, S. E., & Gatti, R. A. (2007) · British Medical Bulletin · doi:10.1093/bmb/ldm012 · Cited by 159 · see citing works
Stern, N., Hochman, A., Zemach, N., Weizman, N., Hammel, I., Shiloh, Y., Rotman, G., & Barzilai, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m106798200 · Cited by 104 · see citing works
DNA double-strand break repair in Caenorhabditis elegans
Lemmens, B. B. L. G., & Tijsterman, M. (2010) · Chromosoma · doi:10.1007/s00412-010-0296-3 · Cited by 76 · see citing works
Lavin, M. F. (2013) · DNA repair · doi:10.1016/j.dnarep.2013.04.014 · Cited by 60 · see citing works
A novel diagnostic tool reveals mitochondrial pathology in human diseases and aging
Scheibye‐Knudsen, M., Scheibye-Alsing, K., Canugovi, C., Croteau, D. L., & Bohr, V. A. (2013) · Aging · doi:10.18632/aging.100546 · Cited by 57 · see citing works
Self-citationMuraki, K., Han, L., Miller, D., & Murnane, J. P. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003386 · Cited by 30 · see citing works
The atm-1 gene is required for genome stability in Caenorhabditis elegans
Jones, M. R., Huang, J. C., Chua, S. Y., Baillie, D. L., & Rose, A. M. (2012) · Molecular Genetics and Genomics · doi:10.1007/s00438-012-0681-0 · Cited by 22 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Verdin E 2015b NAD+ in aging, metabolism, and neurodegeneration Science In press 26785480
Cited by
Sorted by citations
Ageing as a risk factor for neurodegenerative disease
Hou, Y., Dan, X., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., & Bohr, V. A. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0244-7 · Cited by 3,310 · see citing works
Self-citationKlionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationFang, E. F., Hou, Y., Palikaras, K., Adriaanse, B. A., Kerr, J. S., Yang, B., Lautrup, S., Hasan-Olive, M. M., Caponio, D., Dan, X., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0332-9 · Cited by 1,740 · see citing works
Self-citationNAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617 · see citing works
Autophagy in healthy aging and disease
Aman, Y., Schmauck-Medina, T., Hansen, M., Morimoto, R. I., Simon, A. K., Bjedov, I., Palikaras, K., Simonsen, A., Johansen, T., Tavernarakis, N., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00098-4 · Cited by 1,313 · see citing works
Self-citationNAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR
Yoshino, J., Baur, J. A., & Imai, S.-I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.11.002 · Cited by 1,061 · see citing works
Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990 · see citing works
Self-citationMitophagy and Alzheimer’s Disease: Cellular and Molecular Mechanisms
Kerr, J. S., Adriaanse, B. A., Greig, N. H., Mattson, M. P., Cader, M. Z., Bohr, V. A., & Fang, E. F. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.01.002 · Cited by 870 · see citing works
Self-citationTherapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
Rajman, L., Chwalek, K., & Sinclair, D. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.011 · Cited by 865 · see citing works
Self-citationNAD+ in Brain Aging and Neurodegenerative Disorders
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.09.001 · Cited by 790 · see citing works
Self-citationEnhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity
Sorrentino, V., Romani, M., Mouchiroud, L., Beck, J. S., Zhang, H., D’Amico, D., Moullan, N., Potenza, F., Schmid, A. W., Rietsch, S., et al. (2017) · Nature · doi:10.1038/nature25143 · Cited by 630 · see citing works
Mitophagy in human health, ageing and disease
Picca, A., Faitg, J., Auwerx, J., Ferrucci, L., & D’Amico, D. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00930-8 · Cited by 635 · see citing works
NAD(+) in aging: molecular mechanisms and translational implications
Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.08.001 · Cited by 501 · see citing works
Self-citationHou, Y., Lautrup, S., Cordonnier, S., Wang, Y., Croteau, D. L., Zavala, E., Zhang, Y., Moritoh, K., O’Connell, J. F., Baptiste, B. A., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718819115 · Cited by 472 · see citing works
Self-citationDNA damage responses and p53 in the aging process
Ou, H.-L., & Schumacher, B. (2018) · Blood · doi:10.1182/blood-2017-07-746396 · Cited by 377 · see citing works
DNA damage-how and why we age?
Yousefzadeh, M., Henpita, C., Vyas, R., Soto-Palma, C., Robbins, P., & Niedernhofer, L. (2021) · eLife · doi:10.7554/elife.62852 · Cited by 399 · see citing works
Mitophagy: An Emerging Role in Aging and Age-Associated Diseases
Chen, G., Kroemer, G., & Kepp, O. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00200 · Cited by 359 · see citing works
Mitophagy in neurodegeneration and aging
Fivenson, E. M., Lautrup, S., Sun, N., Scheibye-Knudsen, M., Stevnsner, T., Nilsen, H., Bohr, V. A., & Fang, E. F. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.02.007 · Cited by 364 · see citing works
Self-citationRepairing mitochondrial dysfunction in disease
Sorrentino, V., Menzies, K. J., & Auwerx, J. (2018) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104908 · Cited by 337 · see citing works
Nuclear genomic instability and aging
Niedernhofer, L. J., Gurkar, A. U., Wang, Y., Vijg, J., Hoeijmakers, J. H. J., & Robbins, P. D. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012239 · Cited by 275 · see citing works
NAD metabolism: Implications in aging and longevity
Yaku, K., Okabe, K., & Nakagawa, T. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.05.006 · Cited by 269 · see citing works
Pao, P.-C., Patnaik, D., Watson, L. A., Gao, F., Pan, L., Wang, J., Adaikkan, C., Penney, J., Cam, H. P., Huang, W.-C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16361-y · Cited by 216 · see citing works
Connecting aging biology and inflammation in the omics era
Walker, K. A., Basisty, N., Wilson, D. M., & Ferrucci, L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158448 · Cited by 189 · see citing works
Dellinger, R. W., Santos, S. R., Morris, M., Evans, M., Alminana, D., Guarente, L., & Marcotulli, E. (2017) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-017-0016-9 · Cited by 181 · see citing works
Fang, E. F., Waltz, T. B., Kassahun, H., Lu, Q., Kerr, J. S., Morevati, M., Fivenson, E. M., Wollman, B. N., Marosi, K., Wilson, M. A., et al. (2017) · Scientific Reports · doi:10.1038/srep46208 · Cited by 187 · see citing works
Spontaneous DNA damage to the nuclear genome promotes senescence, redox imbalance and aging
Robinson, A. R., Yousefzadeh, M. J., Rozgaja, T. A., Wang, J., Li, X., Tilstra, J. S., Feldman, C. H., Gregg, S. Q., Johnson, C. H., Skoda, E. M., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.04.007 · Cited by 155 · see citing works
The role of PARP1 in neurodegenerative diseases and aging
Mao, K., & Zhang, G. (2022) · The FEBS Journal · doi:10.1111/febs.15716 · Cited by 172 · see citing works
Membrez, M., Migliavacca, E., Christen, S., Yaku, K., Trieu, J., Lee, A. K., Morandini, F., Giner, M. P., Stiner, J., Makarov, M. V., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-00997-x · Cited by 148 · see citing works
“3h,i) and other NAD + boosters 14,42–45 .”
BackgroundMicroglial mitophagy mitigates neuroinflammation in Alzheimer's disease
Lautrup, S., Lou, G., Aman, Y., Nilsen, H., Tao, J., & Fang, E. F. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104469 · Cited by 105 · see citing works
Self-citationde la Rubia, J. E., Drehmer, E., Platero, J. L., Benlloch, M., Caplliure-Llopis, J., Villaron-Casales, C., de Bernardo, N., AlarcÓn, J., Fuente, C., Carrera, S., et al. (2019) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2018.1536152 · Cited by 92 · see citing works
The mitochondrial permeability transition: Nexus of aging, disease and longevity
Rottenberg, H., & Hoek, J. B. (2021) · Cells · doi:10.3390/cells10010079 · Cited by 94 · see citing works
“Of critical importance is sirt 1, which deacetylates a number of critical proteins (87, 104, 105).”
BackgroundToward understanding genomic instability, mitochondrial dysfunction and aging
Fakouri, N. B., Hou, Y., Demarest, T. G., Christiansen, L. S., Okur, M. N., Mohanty, J. G., Croteau, D. L., & Bohr, V. A. (2019) · The FEBS Journal · doi:10.1111/febs.14663 · Cited by 77 · see citing works
Self-citationMolecular mechanisms of mitophagy and its roles in neurodegenerative diseases
Li, X., Huang, L., Lan, J., Feng, X., Li, P., Wu, L., & Peng, Y. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2020.105240 · Cited by 57 · see citing works
Novel Insights into the Anti-Aging Role of Mitophagy
(2018) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2018.05.005 · Cited by 56 · see citing works
DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease
Wang, H., Lautrup, S., Caponio, D., Zhang, J., & Fang, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136748 · Cited by 55 · see citing works
Self-citationStagni, V., Cirotti, C., & Barilà, D. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00073 · Cited by 52 · see citing works
Lloret, A., & Beal, M. F. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02809-1 · Cited by 52 · see citing works
Demarest, T. G., Truong, G. T. D., Lovett, J., Mohanty, J. G., Mattison, J. A., Mattson, M. P., Ferrucci, L., Bohr, V. A., & Moaddel, R. (2019) · Analytical Biochemistry · doi:10.1016/j.ab.2019.02.019 · Cited by 48 · see citing works
Self-citationMetabolic reprogramming: a bridge between aging and tumorigenesis
Drapela, S., Ilter, D., & Gomes, A. P. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13261 · Cited by 41 · see citing works
Inhibition of NAMPT decreases cell growth and enhances susceptibility to oxidative stress
Xu, R., Yuan, Z., Yang, L., Li, L., Li, D., & Lv, C. (2017) · Oncology Reports · doi:10.3892/or.2017.5793 · Cited by 36 · see citing works
Histone Deacetylases 1 and 2 in Memory Function
Pao, P.-C., & Tsai, L.-H. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00775 · Cited by 34 · see citing works
Role and Potential Mechanisms of Nicotinamide Mononucleotide in Aging
Rahman, S. U., Qadeer, A., & Wu, Z. (2024) · Aging and disease · doi:10.14336/ad.2023.0519-1 · Cited by 34 · see citing works
Cros, C., Cannelle, H., Laganier, L., Grozio, A., & Canault, M. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112060 · Cited by 23 · see citing works
NAD+ augmentation with nicotinamide riboside improves lymphoid potential of Atm−/− and old mice HSCs
Zong, L., Tanaka-Yano, M., Park, B., Yanai, H., Turhan, F. T., Croteau, D. L., Tian, J., Fang, E. F., Bohr, V. A., & Beerman, I. (2021) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-021-00078-3 · Cited by 22 · see citing works
Self-citationMolecular Perspectives of Mitochondrial Adaptations and Their Role in Cardiac Proteostasis
Alam, S., Abdullah, C. S., Aishwarya, R., Morshed, M., & Bhuiyan, M. S. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.01054 · Cited by 12 · see citing works
Sun, X., Su, L., Bu, T., & Zhang, Y. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1287421 · Cited by 10 · see citing works
- Authors
- Fang, E. F., Kassahun, H., Croteau, D. L., Scheibye-Knudsen, M., Marosi, K., Lu, H., Shamanna, R. A., Kalyanasundaram, S., Bollineni, R. C., Wilson, M. A., Iser, W. B., Wollman, B. N., Morevati, M., Li, J., Kerr, J. S., Lu, Q., Waltz, T. B., Tian, J., Sinclair, D. A., Mattson, M. P., Nilsen, H., & Bohr, V. A.
- Affiliations
- National Institute on Aging (US)
- University of Oslo (NO)
- National Institutes of Health (US)
- Oslo University Hospital (NO)
- University of Copenhagen (DK)
- Harvard University (US)
- Corresponding author
- Bohr, Vilhelm A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 24
- Issue
- 4
- Pages
- 566-581
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5777858
- OpenAlex
- W2530753724
- Cited by
- 575
- References
- 46
- Citations by year
- 2026: 46 · 2025: 57 · 2024: 69 · 2023: 53 · 2022: 77 · 2021: 85 · 2020: 67 · 2019: 51 · 2018: 33 · 2017: 33 · 2016: 1 · 2015: 1
- FWCI
- 22.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Institute on Aging (R37AG028730)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- ataxia telangiectasia, mitophagy, DNA repair, ATM, poly(ADP-ribosyl)ation, mitochondrial dysfunction, premature aging, lifespan extension, healthspan, neurodegeneration, cerebellar atrophy, DNA double-strand break repair, DNA damage accumulation
- MeSH terms
- Animals, Ataxia Telangiectasia, Behavior, Animal, Cells, Cultured, Disease Models, Animal, DNA Repair, Health, Homeostasis, Longevity, NAD, Neurons, Phenotype, Phthalazines, Piperazines, Signal Transduction, Caenorhabditis elegans, Rats, Sprague-Dawley, Proteomics, Mice, Metabolomics, Gene Knockdown Techniques, Sirtuin 1, Mitophagy, Ataxia Telangiectasia Mutated Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
