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 - 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
AN - SCOPUS:85164561304
SN - 2768-5993
VL - 2
JO - Journal of Cardiovascular Aging
JF - Journal of Cardiovascular Aging
IS - 3
M1 - 28
ER -