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
PY - 2022/4/29
Y1 - 2022/4/29
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.
U2 - 10.20517/jca.2022.13
DO - 10.20517/jca.2022.13
M3 - Article
C2 - 35801078
VL - 2
JO - The journal of cardiovascular aging
JF - The journal of cardiovascular aging
SN - 2768-5993
ER -