The Role of cGAS-STING in Age-Related Diseases from Mechanisms to Therapies

Abstract

With aging, the incidence of age-related diseases increases. Hence, age-related diseases are inevitable. However, the mechanisms by which aging leads to the onset and progression of age-related diseases remain unclear. It has been reported that inflammation is closely associated with age-related diseases and that the cGAS-STING signaling pathway, which can sense the aberrant presence of cytosolic DNA during aging and induce an inflammatory response, is an important mediator of inflammation in age-related diseases. With a better understanding of the structure and molecular biology of the cGAS-STING signaling axis, numerous selective inhibitors and agonists targeting the cGAS-STING pathway in human age-related diseases have been developed to modulate inflammatory responses. Here, we provide a narrative review of the activity of the cGAS-STING pathway in age-related diseases and discuss its general mechanisms in the onset and progression of agerelated diseases. In addition, we outline treatments targeting the cGAS-STING pathway, which may constitute a potential therapeutic alternative for age-related diseases.

Prolyl 4-hydroxylase subunit beta (P4HB) could serve as a prognostic and radiosensitivity biomarker for prostate cancer patients

“…4 c, d). P4HB was predicted to be potential partner of MTTP, P4HA2 and GPX7 using the GeneMANIA [ 24 ] (Fig. 4 e) and STRING databases [ 25 ] (Fig.…”

“…Globally, aging is posing a severe threat to human health [ 16 ]. The vast majority of PCa cases occurred in elderly people and it is anticipated that this trend will worsen as the world’s population ages [ 4 , 17 – 24 ]. There is growing recognition that genetic variability in PCa encompasses many tumor forms with unique biologic characteristics and clinical behaviors [ 25 ].…”

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“…On the other hand, it is speculated to be related to aging. Cellular functions like proliferation, migration, homing, and differentiation are reduced as a result of stress-induced permanent, irreversible cell cycle arrest known as cellular senescence 99 – 102 . The aging of normal cells is a protective mechanism that helps prevent these cells from continuing to divide and proliferate.…”

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“…Upon the activation of the STING protein, various signaling cascades are initiated, ultimately leading to the activation of interferon regulatory factor 3 (IRF3), nuclear factor-kappa B (NF-κB), and the expression of interferon (IFN) and autophagy [97]. Acting as a vital component of the genomic stability system within the cytosol and endolysosomal compartments, the cyclic GMP-AMP synthase (cGAS) detects double-stranded DNA (dsDNA) and functions as an adenosine monophosphate (AMP) synthase [98].…”

“…On the other hand, the cGAS-STING pathway has also been linked to promoting tumor proliferation. Propionibacterium acnes, a common microorganism in normal prostate tissues and PCa, can activate the cGAS-STING pathway and induce the expression of interferons, which subsequently promotes the growth of PCa [98].…”