Novel strategies for anti-aging drug discovery

Saraswat, Komal; Rizvi, Syed Ibrahim

doi:10.1080/17460441.2017.1349750

Cited by 59 publications

(39 citation statements)

References 130 publications

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“…With the aim of reducing off-target effects, other senolytic therapies now moving toward clinical trials are targeting cellular pathways that have greater specificity to senescent cells (Saraswat and Rizvi, 2017). When cells of our immune system (i.e.…”

Section: Discussionmentioning

confidence: 99%

Engineering mammalian cells to seek senescence-associated secretory phenotypes

Qudrat

Wong

Truong

2017

Journal of Cell Science

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Since the removal of senescent cells in model organisms has been linked to rejuvenation and increased lifespan, senotherapies have emerged to target senescent cells for death. In particular, interleukin-6 (IL6) is a prominent senescence-associated secretory phenotype (SASP) and, thus, seeking IL6 could potentially localize engineered cells to senescent cells for therapeutic intervention. Here, we engineered a chimeric IL6 receptor (IL6Rchi) that generates a Ca signal in response to IL6 stimulation. When IL6Rchi was co-expressed with an engineered Ca-activated RhoA (CaRQ), it enabled directed migration to IL6 in cells that have no such natural ability. Next, the removal of target cells was accomplished by the mechanism of membrane fusion and subsequent death. This work represents a first step towards engineering a cell to target senescent cells that secrete high levels of IL6. For increased specificity to senescent cells, it will likely be necessary for an engineered cell to recognize multiple SASPs simultaneously.

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Section: Discussionmentioning

confidence: 99%

Engineering mammalian cells to seek senescence-associated secretory phenotypes

Qudrat

Wong

Truong

2017

Journal of Cell Science

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“…Studies have found that oxidative stress, DNA damage, and inflammation play pivotal roles in age‐associated decline of physiological, genomic, metabolic, and immunological functions . Therefore, anti‐aging therapy and agents targeting these theories are developed, which have dramatically improved human life expectancy . However, based upon our current understanding, more effective and promising approaches for a successful anti‐aging strategy are still needed.…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus and Bifidobacterium Improves Physiological Function and Cognitive Ability in Aged Mice by the Regulation of Gut Microbiota

Ota

Yang

Zheng

et al. 2019

Molecular Nutrition Food Res

189

185

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Scope Age‐related degeneration is associated with imbalances of gut microbiota and its related immune system, thus gut microbiota dysbiosis is considered to be a key target to improve senescence. The potential roles of probiotics on physiological function and cognitive ability in aged mice are investigated in this study. Methods and results Lactobacillus casei LC122 or Bifidobacterium longum BL986, are orally administrated for 12 weeks, and the anti‐aging effects, as well as the composition and function of gut microbiota, are investigated in aged mice. Probiotics supplementation ameliorates hepatic lipid accumulation, enhances muscle strength and function, attenuates oxidative stress and inflammation in peripheral tissues, and improves gut barrier function. These results are associated with improved learning and memory ability as assessed by behavioral tests and upregulation of neurodegenerative and neurotrophic factors expressions in hippocampus. Moreover, the diversity and composition of gut microbiota are altered in aged mice, and both probiotics treatment display distinguished features of gut microbiota. Comparisons of two probiotic strains reveal significant differences in the taxa at family and genus level, leading to the functional profile change of the microbial community. Conclusion L. casei LC122 and B. longum BL986 might be used as novel and promising anti‐aging agents in human.

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“…Autophagy is a conserved essential cellular metabolic pathway in mammalian cells (Lorincz, Mauvezin, & Juhasz, ; Mathai, Meijer, & Simonsen, ; Saraswat & Rizvi, ). Under starvation, hypoxia and oxidative stress, damaged macromolecules and organelles sequestrated in autophagosomes are degraded and recycled through delivery to lysosomes, which ensures cell survival and growth.…”

Section: Introductionmentioning

confidence: 99%

Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity

Shi

et al. 2018

J Tissue Eng Regen Med

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Dental implants have become a widely accepted and successful treatment for fully and partially edentulous patients. Simvastatin has been applied to improve and accelerate the osseointegration of implants by increasing the quantity and quality of bone tissue. However, its potential mechanism has not been elucidated completely. Here, we found that simvastatin significantly enhanced the autophagy level of jaw-derived bone marrow stromal cells (BMSCs) and alleviated production of reactive oxygen species under unfavourable conditions. Simvastatin promoted osteogenic differentiation of BMSCs via enhanced autophagy. Furthermore, simvastatin inhibited the bone resorption activity of osteoclasts. With the use of a rat model of oral implant osseointegration, we found local injection of simvastatin displayed more new bone formation at the interface of the bone and implant compared with that of oral administration. Fluorochrome labelling histomorphometrical analysis and micro-CT also showed that simvastatin promoted the osseointegration of implants. Notably, fewer activated osteoclasts were observed in the region of osseointegration of implants from the simvastatin treatment groups, especially the local delivery of simvastatin. Collectively, our results revealed that simvastatin can increase osteoblastic differentiation of BMSCs via enhanced autophagy and decreased osteoclast activity. Thus, simvastatin could be a viable and promising drug to improve and even accelerate the osseointegration of a dental implant.

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Novel strategies for anti-aging drug discovery

Cited by 59 publications

References 130 publications

Engineering mammalian cells to seek senescence-associated secretory phenotypes

Engineering mammalian cells to seek senescence-associated secretory phenotypes

Lactobacillus and Bifidobacterium Improves Physiological Function and Cognitive Ability in Aged Mice by the Regulation of Gut Microbiota

Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity

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