Premature aging and reduced cancer incidence associated with near-complete body-wide Myc inactivation

Huabo Wang; Jie Lu; Taylor Stevens; Alexander Roberts; Jordan Mandel; Raghunandan Avula; Bingwei Ma; Yijen Wu; Jinglin Wang; Clinton Van t. Land; Toren Finkel; Jerry E. Vockley; Merlin Airik; Rannar Airik; Radhika Muzumdar; Zhenwei Gong; Michel S. Torbenson; Edward V. Prochownik

doi:10.1016/j.celrep.2023.112830

Premature aging and reduced cancer incidence associated with near-complete body-wide Myc inactivation

Huabo Wang, Jie Lu, Taylor Stevens, Alexander Roberts, Jordan Mandel, Raghunandan Avula, Bingwei Ma, Yijen Wu, Jinglin Wang, Clinton Van t. Land, Toren Finkel, Jerry E. Vockley, Merlin Airik, Rannar Airik, Radhika Muzumdar, Zhenwei Gong, Michel S. Torbenson, Edward V. Prochownik

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

Abstract

MYC proto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction and maintenance. Although Myc^+/− mice are healthier and longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe the chronic consequences of body-wide Myc inactivation initiated postnatally. “MycKO” mice acquire numerous features of premature aging, including altered body composition and habitus, metabolic dysfunction, hepatic steatosis, and dysregulation of gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have extended lifespans that correlate with a 3- to 4-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans also downregulate Myc and gradually alter many of the same Myc target gene sets seen in MycKO mice. Normal aging and its associated cancer predisposition are thus highly linked via Myc.

Original language	English (US)
Article number	112830
Journal	Cell reports
Volume	42
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2023.112830
State	Published - Aug 29 2023

Keywords

CP: Cancer
aging

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2023.112830

Cite this

Wang, H., Lu, J., Stevens, T., Roberts, A., Mandel, J., Avula, R., Ma, B., Wu, Y., Wang, J., Land, C. V. T., Finkel, T., Vockley, J. E., Airik, M., Airik, R., Muzumdar, R., Gong, Z., Torbenson, M. S., & Prochownik, E. V. (2023). Premature aging and reduced cancer incidence associated with near-complete body-wide Myc inactivation. Cell reports, 42(8), Article 112830. https://doi.org/10.1016/j.celrep.2023.112830

Wang, H, Lu, J, Stevens, T, Roberts, A, Mandel, J, Avula, R, Ma, B, Wu, Y, Wang, J, Land, CVT, Finkel, T, Vockley, JE, Airik, M, Airik, R, Muzumdar, R, Gong, Z, Torbenson, MS & Prochownik, EV 2023, 'Premature aging and reduced cancer incidence associated with near-complete body-wide Myc inactivation', Cell reports, vol. 42, no. 8, 112830. https://doi.org/10.1016/j.celrep.2023.112830

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abstract = "MYC proto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction and maintenance. Although Myc+/− mice are healthier and longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe the chronic consequences of body-wide Myc inactivation initiated postnatally. “MycKO” mice acquire numerous features of premature aging, including altered body composition and habitus, metabolic dysfunction, hepatic steatosis, and dysregulation of gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have extended lifespans that correlate with a 3- to 4-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans also downregulate Myc and gradually alter many of the same Myc target gene sets seen in MycKO mice. Normal aging and its associated cancer predisposition are thus highly linked via Myc.",

keywords = "CP: Cancer, aging",

author = "Huabo Wang and Jie Lu and Taylor Stevens and Alexander Roberts and Jordan Mandel and Raghunandan Avula and Bingwei Ma and Yijen Wu and Jinglin Wang and Land, {Clinton Van t.} and Toren Finkel and Vockley, {Jerry E.} and Merlin Airik and Rannar Airik and Radhika Muzumdar and Zhenwei Gong and Torbenson, {Michel S.} and Prochownik, {Edward V.}",

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doi = "10.1016/j.celrep.2023.112830",

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AU - Wang, Huabo

AU - Lu, Jie

AU - Stevens, Taylor

AU - Roberts, Alexander

AU - Mandel, Jordan

AU - Avula, Raghunandan

AU - Ma, Bingwei

AU - Wu, Yijen

AU - Wang, Jinglin

AU - Land, Clinton Van t.

AU - Finkel, Toren

AU - Vockley, Jerry E.

AU - Airik, Merlin

AU - Airik, Rannar

AU - Muzumdar, Radhika

AU - Gong, Zhenwei

AU - Torbenson, Michel S.

AU - Prochownik, Edward V.

PY - 2023/8/29

Y1 - 2023/8/29

N2 - MYC proto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction and maintenance. Although Myc+/− mice are healthier and longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe the chronic consequences of body-wide Myc inactivation initiated postnatally. “MycKO” mice acquire numerous features of premature aging, including altered body composition and habitus, metabolic dysfunction, hepatic steatosis, and dysregulation of gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have extended lifespans that correlate with a 3- to 4-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans also downregulate Myc and gradually alter many of the same Myc target gene sets seen in MycKO mice. Normal aging and its associated cancer predisposition are thus highly linked via Myc.

AB - MYC proto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction and maintenance. Although Myc+/− mice are healthier and longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe the chronic consequences of body-wide Myc inactivation initiated postnatally. “MycKO” mice acquire numerous features of premature aging, including altered body composition and habitus, metabolic dysfunction, hepatic steatosis, and dysregulation of gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have extended lifespans that correlate with a 3- to 4-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans also downregulate Myc and gradually alter many of the same Myc target gene sets seen in MycKO mice. Normal aging and its associated cancer predisposition are thus highly linked via Myc.

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KW - aging

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Premature aging and reduced cancer incidence associated with near-complete body-wide Myc inactivation

Abstract

Keywords

ASJC Scopus subject areas

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