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Aging and disease    2017, Vol. 8 Issue (5) : 611-627     DOI: 10.14336/AD.2016.1230
Review |
Cancer and Aging - the Inflammatory Connection
Zinger Adar1, Cho William C2, Ben-Yehuda Arie1,*
1Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
2Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
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Aging and cancer are highly correlated biological phenomena. Various cellular processes such as DNA damage responses and cellular senescence that serve as tumor suppressing mechanisms throughout life result in degenerative changes and contribute to the aging phenotype. In turn, aging is considered a pro-tumorigenic state, and constitutes the single most important risk factor for cancer development. However, the causative relations between aging and cancer is not straight forward, as these processes carry contradictory hallmarks; While aging is characterized by tissue degeneration and organ loss of function, cancer is a state of sustained cellular proliferation and gain of new functions. Here, we review the molecular and cellular pathways that stand in the base of aging related cancer. Specifically, we deal with the inflammatory perspective that link these two processes, and suggest possible molecular targets that may be exploited to modify their courses.

Keywords aging      cancer      senescence      inflammation      immunosenescence      autophagy     
Corresponding Authors: Ben-Yehuda Arie   
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These authors contribute equally to the manuscript

Issue Date: 01 October 2017
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Zinger Adar
Cho William C
Ben-Yehuda Arie
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Zinger Adar,Cho William C,Ben-Yehuda Arie. Cancer and Aging - the Inflammatory Connection[J]. Aging and disease, 2017, 8(5): 611-627.
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Figure 1.  Aging-related cancer

Exposure to various endogenous and exogenous stressors throughout life results in multiple cellular and tissue function changes. Accumulation of senescent cells in the tissue is associated with tissue degeneration and SASP-related changes of the microenvironment. Functional changes in aging immune system along with DAMPs-associated immune responses contribute to the ensemble of inflammatory processes that accompanies the aging process, so-called “inflammaging”. This unique inflammatory network joins intracellular processes including changes in chromatin function and reduction in autophagy capacity, and to changes in the microbiome and intestinal barrier dysfunction, to create a pro-tumorigenic environment.

Figure 2.  SASP regulation

SASP is under a regulation of multifactorial singaling networks. The DDR effectors NBS1, ATM and CHK2 upregulate SASP. Importantly, p53 is a negative regulator of SASP and serves to restrain it upon DDR activation. mTOR positively regulates SASP via activation of the MAPK p38 pathway, and upregulation of IL-1α. Chromatin reorganization in senescent cells involves newly activated super enhancer (SE) elements. BRD4 is recruited to the SE and participate in the regulation of key SASP genes. NOTCH1 was indentified as a modulator of SASP composition in oncogene-induced senescent cells.

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