Autophagy in aging and longevity Wong, Shi Q.; Kumar, Anita V.; Mills, Joslyn ...
Human Genetics,
03/2020, Letnik:
139, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Our understanding of the process of autophagy and its role in health and diseases has grown remarkably in the last two decades. Early work established autophagy as a general bulk recycling process ...which involves the sequestration and transport of intracellular material to the lysosome for degradation. Currently, autophagy is viewed as a nexus of metabolic and proteostatic signalling that can determine key physiological decisions from cell fate to organismal lifespan. Here, we review the latest literature on the role of autophagy and lysosomes in stress response and longevity. We highlight the connections between autophagy and metabolic processes, the network associated with its regulation, and the links between autophagic dysfunction, neurodegenerative diseases, and aging.
Efficient proteostasis is crucial for somatic maintenance, and its decline during aging leads to cellular dysfunction and disease. Selective autophagy is a form of autophagy mediated by receptors ...that target specific cargoes for degradation and is an essential process to maintain proteostasis. The protein Sequestosome 1 (p62/SQSTM1) is a classical selective autophagy receptor, but it also has roles in the ubiquitin-proteasome system, cellular metabolism, signaling, and apoptosis. p62 is best known for its role in clearing protein aggregates via aggrephagy, but it has recently emerged as a receptor for other forms of selective autophagy such as mitophagy and lipophagy. Notably, p62 has context-dependent impacts on organismal aging and turnover of p62 usually reflects active proteostasis. In this review, we highlight recent advances in understanding the role of p62 in coordinating the ubiquitin-proteasome system and autophagy. We also discuss positive and negative effects of p62 on proteostatic status and their implications on aging and neurodegeneration. Finally, we relate the link between defective p62 and diseases of aging and examine the utility of targeting this multifaceted protein to achieve proteostatic benefits.
•The extended Theory of Planned Behaviour l model to test young adults’ Intention to Recycle e-waste cross-culturally indicated a strong fit (R2 0.572, p < 0.001).•Attitude (moderated by a Sense of ...Duty), Perceived Control, Subjective Norm and Individual Responsibility constructs had significant influence on the model fit whereas Convenience and Consequences Awareness constructs had no influence.•Cross-cultural differences were also evident as stronger relationships were witnessed for Perceived Control and Subjective Norm constructs for the Chinese sample.•The reverse was found to be true for Attitude (moderated by a Sense of Duty) and Individual Responsibility constructs where stronger relationships were observed in the Indian sample.
The objective of this research is to explore young adults’ e-waste recycling behaviour cross-culturally using an extended Theory of planned Behaviour (TPB) model. The results of a survey involving respondents from the two culturally-distinct emerging markets showed that the key influencing factors that influenced e-waste recycling behaviour amongst young adults were: Attitude (moderated by a Sense of Duty), Perceived Control, Subjective Norm and Individual Responsibility whereas Convenience and Consequences Awareness constructs did not have significant influence. Cross-cultural differences were also evident as stronger relationships were witnessed for Perceived Control and Subjective Norm constructs for the Chinese young adults’ intention to recycle e-waste. The reverse was found to be true for Attitude (moderated by a Sense of Duty) and Individual Responsibility constructs where stronger relationships were observed in the Indian sample. This research makes a valuable theoretical contribution as it is positioned at the intersection of cross-cultural studies, sustainability and reverse supply chain management areas. This study has practical implication at two levels: the individual actor level and the supply chain level as consumers’ intentions to recycle, underpinned by responsibility towards environment, directly impact the performance of reverse supply chains.
Spermatogenesis occurs in the seminiferous epithelium that shows the presence of estrogen receptors alpha (ERα) and beta (ERβ), both of which regulate gene transcription by binding to the DNA. ...Estrogen responsive phases of spermatogenesis are well documented; however, the genes regulated remain inexplicit. To study the regulation of genes by estrogen in male germ cells, we performed chromatin immunoprecipitation (ChIP) sequencing for ERα and ERβ under normal physiological conditions. A total of 27 221 DNA binding regions were enriched with ERα and 20 926 binding sites with ERβ. Majority of the peaks were present in the intronic regions and located 20 kb upstream or downstream from the transcription start site (TSS). Pathway analysis of the genes enriched by ChIP-Seq showed involvement in several biological pathways. Genes involved in pathways whose role in spermatogenesis is unexplored were validated; these included prolactin, GnRH, and oxytocin signaling. All the selected genes showed the presence of estrogen response elements (EREs) in their binding region and were also found to be significantly enriched by ChIP-qPCR. Functional validation using seminiferous tubule culture after treatment with estrogen receptor subtype-specific agonist and antagonist confirmed the regulation of these genes by estrogen through its receptors. The genes involved in these pathways were also found to be regulated by the respective receptor subtypes at the testicular level in our in vivo estrogen receptor agonist rat models. Our study provides a genome-wide map of ERα and ERβ binding sites and identifies the genes regulated by them in the male germ cells under normal physiological conditions.
In this paper, an early childhood teacher educator and researcher describes the experience of facilitating and enacting a practice-focused course design for preservice early childhood teachers. The ...course utilized video analysis, practice records, rehearsal pedagogies and a focus on teacher-child interactions. The author reflects on the structure and facilitation used to help preservice teachers in engaging with these course elements. The facilitation processes employed around the practice-focused teaching-learning activities helped the PSTs engage with representations, decomposition, and approximations of practice to learn about effective teacher-child interactions, a core practice in early childhood education. Implications for early childhood teacher education are discussed.
The novel coronavirus, SARS-CoV-2, has caused a global pandemic with high morbidity and mortality. It was first observed to cause a severe acute respiratory syndrome. However, gastrointestinal and ...hepatic manifestations have been increasingly recognized. Gastrointestinal symptoms include diarrhea, epigastric pain, nausea, and vomiting. Diarrhea is the most common GI manifestation of SARS-CoV-2 and can present without or without respiratory symptoms. Patients with GI symptoms have been associated with longer duration of illness and may be associated with more severe illness. Mechanism of diarrhea is thought to be related to direct viral cytotoxicity occurring when the SARS-CoV-3 enters GI cells via the ACE-2 receptor. Inflammatory response and cytokine release likely contributes to symptoms. SARS-CoV-2 can cause hepatic injury. Studies have shown mild to moderate elevation of liver enzymes. The pattern of liver abnormalities can be hepatocellular, cholestatic or mixed. Patients with severe infection have significantly higher rates of liver injury and worse outcomes. Proposed mechanisms for injury include immune mediated systemic inflammatory response, direct cytotoxicity from viral replication and hypoxia-reperfusion dysfunction. Recent data suggests that GI and hepatic injury may be under-recognized manifestation of SARS-CoV-2 infection. Patients with diarrhea and liver disease may have a worse prognosis. The rapidly evolving literature continues to reveal a growing body of information which enables updated guidance for management. More investigation is needed which focuses on vulnerable patients, including the elderly, those with underlying illness, as well as, racial and ethnic minorities.
PDF
