Hallmarks of Aging: An Autophagic Perspective

Barbosa, María Carolina; Grosso, Rubén Adrián; Fader, Claudio Marcelo

doi:10.3389/fendo.2018.00790

Cited by 204 publications

(174 citation statements)

References 144 publications

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“…Ideally, evidence consistently shows that autophagy also plays an important role in cell differentiation and development. Beclin-1 and microtubule-associated light chain 3 (LC3) are the major autophagic proteins involved in the formation of autophagosomes (18,19). Early changes in these proteins may affect our further study of bone development.…”

Section: Discussionmentioning

confidence: 99%

Puerarin promotes the viability and differentiation of MC3T3‑E1 cells by enhancing LC3B‑mediated autophagy through downregulation of miR‑204

et al. 2019

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Puerarin is a bioactive substance extracted from Pueraria lobata. It is known to promote the viability, differentiation and mineralization of osteoblasts. However, the molecular mechanisms involved in these activities are not well understood. The present study was conducted with the aim of elucidating the effect of puerarin on osteoblasts and to explore the underlying mechanism. CCK-8 analysis showed that puerarin (0.1, 1 and 10 µM) promoted the viability of osteoblastic MC3T3-E1 cells, with 1 µM of puerarin exhibiting the strongest effect. Moreover, 1 µM puerarin significantly increased the activity of alkaline phosphatase (ALP) and the formation of mineralized nodules in the MC3T3-E1 cells. Treatment with 1 µM puerarin for 72 h led to a significant upregulation in the expression level of microtubule-associated light chain 3 (LC3)B and Beclin1 proteins. This treatment was more effective in promoting LC3B expression than what was observed following treatment with rapamycin (overexpression for autophagy). The bilayer membrane structure of autophagosomes was observed by electron microscopy. Conversely, 3-methyladenine (3-MA, inhibitor of autophagy) reduced the cell viability as well as the activity of alkaline phosphatase (ALP) in MC3T3-E1 cells, although, there was no significant influence on mineralization. Prediction results of the biological information showed that LC3B could be a direct target of . In the present study, the expression level of miR-204 was decreased by puerarin. miR-204 mimics significantly decreased LC3B expression and inhibited auotophagosome formation, while the miR-204 inhibitor had the opposite effects. To conclude, the results of the present study suggest that puerarin promotes the viability and differentiation of MC3T3-E1 cells through autophagy, which is possibly associated with miR-204-regulated LC3B upregulation.

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Section: Discussionmentioning

confidence: 99%

Puerarin promotes the viability and differentiation of MC3T3‑E1 cells by enhancing LC3B‑mediated autophagy through downregulation of miR‑204

et al. 2019

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“…It is now apparent that the principle of SCV, and related machine learning approaches (50), will be essential to understand the role of the client and their associated PN network in managing protein folding in response to aging and to environmental stress related challenges (9). SCV principles will also be critical to understand the functionality of the proteome in the context of genome design and transcriptome responses that generate the protective barriers (3,35) and CARE, as shown herein, that limit or attempt to limit the impact of aging-and pathology-associated stress to achieve a more sustainable level of lung function over a lifespan (13,(89)(90)(91)(92).…”

Section: Discussionmentioning

confidence: 99%

Proteostasis and Energetics as Proteome Hallmarks of Aging and Influenza Challenge in Pulmonary Disease

Loguercio

Hutt

Campos

et al. 2019

Preprint

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Aging is associated with an increased risk for the development of many diseases. This is exemplified by the increased incidence of lung injury, muscle dysfunction and cognitive impairment in the elderly following influenza infection. Because the infectious cycle of flu is dependent upon the properties of the host, we examined the proteome of alveolar macrophages (AM) and type 2 cells (AT2) obtained from young (3 months) and old (18 months) naïve mice and mice exposed to influenza A. Our proteomics data show that there is a maladaptive collapse of the proteostasis network (PN) and changes in mitochondrial pathways in the aged naïve AM and AT2 proteomes. The mitochondrial imbalance and proteostatic collapse seen in aged cells places an excessive folding burden on these cells, which is further exacerbated following exposure to influenza A. Specifically, we see an imbalance in Hsp70 co-chaperones involved in protein folding and Hsp90 co-chaperones important for stress signaling pathways that are essential for cellular protection during aging. The acute challenge of influenza A infection of young and aged AM and AT2 cells reveals that age-associated changes in the chaperome affect the ability of these cells to properly manage the infection and post-infection biology, contributing to cytotoxicity. We posit that proteomic profiling of individual cell type specific responses provides a high impact approach to pinpoint fundamental molecular relationships that may contribute to the susceptibility to aging and environmental stress, providing a platform to identify new targets for therapeutic intervention to improve resiliency in the elderly.

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“…(1) CR will not enhance longevity in long-lived species, including primates, because metabolic stability determines longevity, and different species have dif-ferent life history adaptations (Demetrius 2005), (2) any beneficial effect of CR on longevity stems from the lowering of oxidative stress and the attenuation of inflammation (Yu 2006), (3) CR can work through the inhibition of mTOR (Blagosklonny 2010) and 4the effects of CR on health might be partly attributed to the stimulation of autophagy (Terman et al 2007;Barbosa et al 2019). Unlike evolutionary explanations, points (2-4) refer to the mechanistic causes and have important limitations as they fail to provide a comprehensive understanding of CR effects on health and longevity in different species with different life history adaptations.…”

Section: Can Calorie Restriction Delay the Onset Of Age-related Disease?mentioning

confidence: 99%

The dynamic nature of ageing: novel findings, therapeutic avenues and medical interventions

Chmielewski

2020

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Ageing is one of the most complex and difficult problems for humans to face and for science to solve. Although human senescence was viewed as a passive and uncontrollable process of deterioration over time with little or no genetic regulation, the concept that ageing is caused by both genetic and environmental factors is now generally accepted, even though it remains difficult to distinguish between ageing sensu stricto and the effects of age-related diseases. Empirical data show that mechanisms of ageing are highly conserved during evolution. Moreover, it has been established that there are specific molecular ‘instructions’ for ageing, which suggests that a better understanding of the molecular biology of ageing will open new possibilities regarding future interventions. The complexity of ageing diminishes the possibility that any general theory will completely explain this metaphenomenon. Likewise, it is highly unlikely that any medication can stop or reverse human senescence. Nevertheless, ageing as a dynamic and malleable metaphenomenon can be modulated by a variety of influences. The concept of the shrinkage of the homeo-dynamic space with age, i.e. homeostenosis, is especially interesting and intriguing as it shows that novel therapeutic approaches and rational strategies can help delay the onset of the ageing-associated pathologies by enhancing the homeodynamic capabilities of the body. The aim of this article is to present current data from evolutionary and molecular gerontology and discuss them within the ambit of this review which is devoted to the dynamic, emergent and plastic nature of human ageing and implications for future interventions.

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Hallmarks of Aging: An Autophagic Perspective

Cited by 204 publications

References 144 publications

Puerarin promotes the viability and differentiation of MC3T3‑E1 cells by enhancing LC3B‑mediated autophagy through downregulation of miR‑204

Puerarin promotes the viability and differentiation of MC3T3‑E1 cells by enhancing LC3B‑mediated autophagy through downregulation of miR‑204

Proteostasis and Energetics as Proteome Hallmarks of Aging and Influenza Challenge in Pulmonary Disease

The dynamic nature of ageing: novel findings, therapeutic avenues and medical interventions

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