NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair

Research output: Contribution to journal › Journal article › Research › peer-review

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NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. / Fang, Evandro Fei; Kassahun, Henok; Croteau, Deborah L; Scheibye-Knudsen, Morten; Marosi, Krisztina; Lu, Huiming; Shamanna, Raghavendra A; Kalyanasundaram, Sumana; Bollineni, Ravi Chand; Wilson, Mark A; Iser, Wendy B; Wollman, Bradley N; Morevati, Marya; Li, Jun; Kerr, Jesse S; Lu, Qiping; Waltz, Tyler B; Tian, Jane; Sinclair, David A; Mattson, Mark P; Nilsen, Hilde; Bohr, Vilhelm A.

In: Cell Metabolism, Vol. 24, No. 4, 11.10.2016, p. 566-581.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Fang, EF, Kassahun, H, Croteau, DL, Scheibye-Knudsen, M, Marosi, K, Lu, H, Shamanna, RA, Kalyanasundaram, S, Bollineni, RC, Wilson, MA, Iser, WB, Wollman, BN, Morevati, M, Li, J, Kerr, JS, Lu, Q, Waltz, TB, Tian, J, Sinclair, DA, Mattson, MP, Nilsen, H & Bohr, VA 2016, 'NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair', Cell Metabolism, vol. 24, no. 4, pp. 566-581. https://doi.org/10.1016/j.cmet.2016.09.004

APA

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., ... Bohr, V. A. (2016). NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. Cell Metabolism, 24(4), 566-581. https://doi.org/10.1016/j.cmet.2016.09.004

Vancouver

Fang EF, Kassahun H, Croteau DL, Scheibye-Knudsen M, Marosi K, Lu H et al. NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. Cell Metabolism. 2016 Oct 11;24(4):566-581. https://doi.org/10.1016/j.cmet.2016.09.004

Author

Fang, Evandro Fei ; Kassahun, Henok ; Croteau, Deborah L ; Scheibye-Knudsen, Morten ; Marosi, Krisztina ; Lu, Huiming ; Shamanna, Raghavendra A ; Kalyanasundaram, Sumana ; Bollineni, Ravi Chand ; Wilson, Mark A ; Iser, Wendy B ; Wollman, Bradley N ; Morevati, Marya ; Li, Jun ; Kerr, Jesse S ; Lu, Qiping ; Waltz, Tyler B ; Tian, Jane ; Sinclair, David A ; Mattson, Mark P ; Nilsen, Hilde ; Bohr, Vilhelm A. / NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. In: Cell Metabolism. 2016 ; Vol. 24, No. 4. pp. 566-581.

Bibtex

@article{d90e6e9a755243f58465b456137ef7b7,
title = "NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair",
abstract = "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.",
author = "Fang, {Evandro Fei} and Henok Kassahun and Croteau, {Deborah L} and Morten Scheibye-Knudsen and Krisztina Marosi and Huiming Lu and Shamanna, {Raghavendra A} and Sumana Kalyanasundaram and Bollineni, {Ravi Chand} and Wilson, {Mark A} and Iser, {Wendy B} and Wollman, {Bradley N} and Marya Morevati and Jun Li and Kerr, {Jesse S} and Qiping Lu and Waltz, {Tyler B} and Jane Tian and Sinclair, {David A} and Mattson, {Mark P} and Hilde Nilsen and Bohr, {Vilhelm A}",
note = "Published by Elsevier Inc.",
year = "2016",
month = oct,
day = "11",
doi = "10.1016/j.cmet.2016.09.004",
language = "English",
volume = "24",
pages = "566--581",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair

AU - Fang, Evandro Fei

AU - Kassahun, Henok

AU - Croteau, Deborah L

AU - Scheibye-Knudsen, Morten

AU - Marosi, Krisztina

AU - Lu, Huiming

AU - Shamanna, Raghavendra A

AU - Kalyanasundaram, Sumana

AU - Bollineni, Ravi Chand

AU - Wilson, Mark A

AU - Iser, Wendy B

AU - Wollman, Bradley N

AU - Morevati, Marya

AU - Li, Jun

AU - Kerr, Jesse S

AU - Lu, Qiping

AU - Waltz, Tyler B

AU - Tian, Jane

AU - Sinclair, David A

AU - Mattson, Mark P

AU - Nilsen, Hilde

AU - Bohr, Vilhelm A

N1 - Published by Elsevier Inc.

PY - 2016/10/11

Y1 - 2016/10/11

N2 - 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.

AB - 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.

U2 - 10.1016/j.cmet.2016.09.004

DO - 10.1016/j.cmet.2016.09.004

M3 - Journal article

C2 - 27732836

VL - 24

SP - 566

EP - 581

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 4

ER -

ID: 169440364