2017
DOI: 10.18632/aging.101319
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Abstract: Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort t… Show more

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Cited by 70 publications
(62 citation statements)
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References 186 publications
(227 reference statements)
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“…We performed an interaction-based similarity analysis and found that the genotoxic compounds cluster separately from the other drugs, suggesting that they have a similar mechanism of action (S2 text). Similarities were also identified regarding the mechanisms of action of sorafenib and regorafenib, bexarotene and GW-501516, and sirolimus and ECGC, in agreement with previous studies [36].…”
Section: Resultssupporting
confidence: 90%
“…In the present study, we show that ISLQ treatment increases cellular ROS, and that this is involved in mediating the cytotoxic effects of ISLQ on human NB cells. It is also worth noting that a recent study identified ISLQ as a natural mimetic of rapamycin [68], which is an FDA-approved mTOR inhibitor that has anti-carcinogenic effects in NB cells [69]. Treatment of NB cells with rapamycin for 24 h has been shown to increase cellular levels of ROS [70], which is consistent with the increases in cellular oxidative stress in MYCN-amplified SK-N-BE(2) cells induced by ISLQ treatment for 24 h, found in our study.…”
Section: Discussionmentioning
confidence: 99%
“…One of the most impactful applications of DL in biomedicine was in the applications of generative models to de novo molecular design [32][33][34][35][36] . In the context of aging research, these new methods can be combined for geroprotector discovery [37][38][39][40][41] . Indeed, since 2013, many aging clocks have been developed in both humans and other model organisms.…”
Section: Introductionmentioning
confidence: 99%
“…Similarly, W. somnifera decreased MDA (a secondary product of LPO) levels in patients with type‐2 diabetes (Usharani, Fatima, et al, ; Usharani, Kishan, et al, ). The observed antioxidant activities of W. somnifera might be, majorly, attributed to its active constituent withaferin A—a steroidal lactone (Aliper et al, ; Lee et al, ) as well other bioactive elements—steroidal alkaloids/lactones such as withanine, somniferine, withanone sitoindosides VII–X and withanolide A, D and G (Durg et al, ; Mirjalili, Moyano, Bonfill, Cusido, & Palazón, ).…”
Section: Discussionmentioning
confidence: 99%
“…W. somnifera also showed glucose lowering activity through insulinotropic effects which improves insulin sensitivity by reducing hyperinsulinemia and insulin resistant besides improving glucose tolerance (Anwer et al, ). The recent in ‐ silico screening revealed that withaferin A mimics the anti‐aging properties of mTOR inhibitors, that is, metformin and rapamycin (Aliper et al, ); the two FDA‐approved drugs which tops the list of drugs mimicking caloric restriction (Ingram et al, ). Further, Lee et al demonstrated withaferin A as a potential leptin sensitizer with great anti‐diabetic effects in mice (Lee et al, ).…”
Section: Discussionmentioning
confidence: 99%