TY - JOUR
T1 - Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications
AU - Banerjee, Priyanka
AU - Olmsted-Davis, Elizabeth A.
AU - Deswal, Anita
AU - Nguyen, Minh Th
AU - Koutroumpakis, Efstratios
AU - Palaskas, Nicholas L.
AU - Lin, Steven H.
AU - Kotla, Sivareddy
AU - Reyes-Gibby, Cielito
AU - Yeung, Sai Ching J.
AU - Yusuf, Syed Wamique
AU - Yoshimoto, Momoko
AU - Kobayashi, Michihiro
AU - Yu, Bing
AU - Schadler, Keri
AU - Herrmann, Joerg
AU - Cooke, John P.
AU - Jain, Abhishek
AU - Chini, Eduardo
AU - Le, Nhat Tu
AU - Abe, Jun Ichi
N1 - Funding Information:
This work was partially supported by grants from the National Institutes of Health (NIH) to Drs. Abe (AI156921), Cooke (HL-149303), Chini (AG26094, AG58812, and CA233790), Le (HL-149303), and from Cancer Prevention and Research Institute of Texas (CPRIT) to Drs. Abe and Schadler (RP190256). This work is supported in part by the MD Anderson Cancer Center Support Grant CA016672. Dr. Deswal is supported in part by the Ting Tsung and Wei Fong Chao Distinguished Chair. The Glenn Foundation for Medical Research via the Paul F. Glenn Laboratories for the Biology of Aging, Calico Life Sciences LLC to E.N.C.
Publisher Copyright:
© The Author(s) 2022. Open Access.
PY - 2022/7
Y1 - 2022/7
N2 - Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family that is not only a kinase but also a transcriptional co-activator) were vital signaling events that played crucial roles in linking mitochondrial dysfunction, nuclear telomere dysfunction, persistent SASP induction, and atherosclerosis. In this review, we will discuss the role of NAD+ depletion in instigating SASP and its downstream signaling and regulatory mechanisms that lead to the premature onset of atherosclerotic cardiovascular diseases in cancer survivors.
AB - Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family that is not only a kinase but also a transcriptional co-activator) were vital signaling events that played crucial roles in linking mitochondrial dysfunction, nuclear telomere dysfunction, persistent SASP induction, and atherosclerosis. In this review, we will discuss the role of NAD+ depletion in instigating SASP and its downstream signaling and regulatory mechanisms that lead to the premature onset of atherosclerotic cardiovascular diseases in cancer survivors.
KW - ERK5
KW - NAD
KW - cardiovascular diseases
KW - p90RSK
KW - senescence-associated secretory phenotype (SASP)
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U2 - 10.20517/jca.2022.13
DO - 10.20517/jca.2022.13
M3 - Review article
C2 - 35801078
SN - 2768-5993
VL - 2
JO - The journal of cardiovascular aging
JF - The journal of cardiovascular aging
IS - 3
M1 - 28
ER -