From rapalogs to anti-aging formula

Blagosklonny, Mikhail V.

doi:10.18632/oncotarget.18033

Cited by 77 publications

(62 citation statements)

References 246 publications

(215 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rapamycin, a specific inhibitor of mechanistic target of rapamycin (mTOR) signalling with many effects, including anti-inflammatory activity 265 , has an important role in longevity regulation 266 in both animals and humans 267 , and improves survival and healthspan in animal models 268–272 . Aspirin improves lifespan in mice 273 , whereas metformin, which is known to have direct anti-inflammatory effects beyond its canonical glucose-lowering activity 274 , improves lifespan and healthspan in animal models 275 .…”

Section: Inflammageing Is a Pillar Of Gerosciencementioning

confidence: 99%

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

2018

View full text Add to dashboard Cite

Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty — which affect clinical manifestations, prognosis, and response to treatment — and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.

show abstract

Section: Inflammageing Is a Pillar Of Gerosciencementioning

confidence: 99%

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

2018

View full text Add to dashboard Cite

show abstract

“…Lupus and Sjogren's syndrome occur when mTOR is activated, and its blockade with rapamycin is therapeutically effective [70]. Recent investigations have demonstrated that both mTOR and rapamycin have pivotal roles of antiaging, development, various diseases such as cancer, diabetes, obesity and also tissue injury [71][72][73][74][75][76]. Aging is a continuation of developmental growth [75], and rapamycin slows aging by inhibitory effects on mTOR driving conversion from quiescence to senescence (geroconversion) [76,77].…”

Section: Discussionmentioning

confidence: 99%

Role of the mTOR signalling pathway in salivary gland development

et al. 2019

View full text Add to dashboard Cite

Development of the salivary gland is characterized by extensive branching morphogenesis. Although various molecules have been implicated in salivary gland development, the role of the mammalian target of rapamycin (mTOR) signalling pathway, including both mTOR complexes 1 and 2 (mTORC1 and 2), in salivary gland development is unknown. Here, we examined protein expression levels related to the mTOR signalling pathway using an ex vivo submandibular salivary gland (SMG) organ culture. We showed that branching buds in the salivary glands were substantially decreased and phosphorylation of mTORC1 signalling pathway related proteins (mTOR, p70 ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E‐binding protein 1) was inhibited by rapamycin (an mTOR inhibitor). In addition, AKT, which is an upstream protein kinase of mTORC1 and is downstream of mTORC2, is inhibited by LY294002 (a phosphatidylinositol 3‐kinase inhibitor), but not by rapamycin. Moreover, rapamycin‐treated ICR neonatal mice exhibited a reduction in both body weight and salivary glands compared with vehicle‐treated neonatal mice. The present data indicate that the mTOR signalling pathway, including both mTORC1 and mTORC2, plays a critical role in salivary gland development both in ex vivo SMG organ culture and ICR neonatal mice in vivo.

show abstract

“…Besides activation of the survival kinase Akt, activation of the growth kinase mTOR kinase has been shown to be crucial for geroconversion. In that regard, the establishment of the senescent phenotype is accompanied by an increase in the activity of mTOR, which is considered as a hallmark of organismal aging . mTOR inhibition extends life span and improves age‐related pathologies in a variety of species .…”

Section: Oxidants and Cellular Senescence Beyond Cell Cycle Arrestmentioning

confidence: 99%

“…In that regard, the establishment of the senescent phenotype is accompanied by an increase in the activity of mTOR, which is considered as a hallmark of organismal aging. [104][105][106] mTOR inhibition extends life span and improves age-related pathologies in a variety of species. [80,[106][107][108] Interestingly, a recent report established that mTOR is activated through a PI3K/Akt/mTOR pathway during replicative senescence in vascular smooth muscle cells.…”

Section: Oxidants and Geroconversionmentioning

confidence: 99%

Organismal Aging and Oxidants beyond Macromolecules Damage

Clément

Luo

2020

Proteomics

View full text Add to dashboard Cite

The relationship between oxidants and organismal aging was first articulated through the free radical theory of aging. One of the major predictions of the free radical theory of aging is that oxidative stress shortens organisms’ lifespan because of an increased level of oxidants, which are damaging to macromolecules. However, challenging the role of oxidants in age‐related diseases, there is now sufficient evidence that antioxidant supplements do not provide significant health benefits. Interestingly, in addition to an increase in oxidant‐mediated macromolecules damage, there is convincing experimental data to support the role of senescent cells in the process of aging. Here, the current knowledge regarding the role of oxidants and cellular senescence in organismal aging is reviewed and it is proposed that, in addition to the role of oxidants as inducers of macromolecular damage, oxidants may also function as regulators of signaling pathways involved in the establishment of cellular senescence. If this role for oxidants is established, it may be necessary to modify the free radical theory of aging from “Organisms age because cells accumulate reactive oxygen species‐dependent damage over time” to: “Organisms age because cells accumulate oxidants’‐dependent damage and oxidants’‐dependent senescent characteristics over time.”

show abstract

From rapalogs to anti-aging formula

Cited by 77 publications

References 246 publications

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Role of the mTOR signalling pathway in salivary gland development

Organismal Aging and Oxidants beyond Macromolecules Damage

Contact Info

Product

Resources

About