TFEB is a central regulator of the aging process and age-related diseases

Abokyi, Samuel; Ghartey‐Kwansah, George; Tse, Dennis Y.

doi:10.1016/j.arr.2023.101985

Cited by 11 publications

(5 citation statements)

References 193 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are a variety of natural compounds able to induce autophagy that are not extensively studied. Trehalose, a disaccharide sugar, stimulates autophagy independently of mTOR by activating transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy-related gene expression [ 162 , 163 ]. Preclinically, trehalose clears misfolded and aggregated proteins in cells and a mouse neurodegeneration model, reducing brain atrophy [ 164 , 165 ].…”

Section: Current Targets Of Aging Interventionsmentioning

confidence: 99%

Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks

Yusri,

Kumar,

Fong

et al. 2024

IJMS

View full text Add to dashboard Cite

Aging is a complex and time-dependent decline in physiological function that affects most organisms, leading to increased risk of age-related diseases. Investigating the molecular underpinnings of aging is crucial to identify geroprotectors, precisely quantify biological age, and propose healthy longevity approaches. This review explores pathways that are currently being investigated as intervention targets and aging biomarkers spanning molecular, cellular, and systemic dimensions. Interventions that target these hallmarks may ameliorate the aging process, with some progressing to clinical trials. Biomarkers of these hallmarks are used to estimate biological aging and risk of aging-associated disease. Utilizing aging biomarkers, biological aging clocks can be constructed that predict a state of abnormal aging, age-related diseases, and increased mortality. Biological age estimation can therefore provide the basis for a fine-grained risk stratification by predicting all-cause mortality well ahead of the onset of specific diseases, thus offering a window for intervention. Yet, despite technological advancements, challenges persist due to individual variability and the dynamic nature of these biomarkers. Addressing this requires longitudinal studies for robust biomarker identification. Overall, utilizing the hallmarks of aging to discover new drug targets and develop new biomarkers opens new frontiers in medicine. Prospects involve multi-omics integration, machine learning, and personalized approaches for targeted interventions, promising a healthier aging population.

show abstract

Section: Current Targets Of Aging Interventionsmentioning

confidence: 99%

Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks

Yusri,

Kumar,

Fong

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…A growing number of experimental results show that transcription factors (TFs) are involved in the modulation of age-related disorders, including cancer and neurodegenerative diseases. They play a crucial role as regulators of many important cellular processes, including mitochondrial biogenesis, energy metabolism, oxidative stress, DNA repair, inflammation, nutrient homeostasis, vascular development, and cell regenerative capacity [56]. For example, transcription factor EB (TFEB) participates in the regulation of DNA damage and epigenetic modifications, inducing autophagy and proteostasis, regulating mitochondrial quality control, and linking nutrient sensing to energy metabolism.…”

Section: Transcription Factorsmentioning

confidence: 99%

“…TFEB also modulates pro-and anti-inflammatory pathways, suppresses senescence, and stimulates cell regeneration. Safe and effective strategies for activating TFEB might be considered 6 of 18 as a therapeutic approach for cancer and neurodegenerative disease treatment and for extending longevity [56].…”

Section: Transcription Factorsmentioning

confidence: 99%

Association between Parkinson’s Disease and Cancer: New Findings and Possible Mediators

Surguchov,

Surguchev

2024

IJMS

View full text Add to dashboard Cite

Epidemiological evidence points to an inverse association between Parkinson’s disease (PD) and almost all cancers except melanoma, for which this association is positive. The results of multiple studies have demonstrated that patients with PD are at reduced risk for the majority of neoplasms. Several potential biological explanations exist for the inverse relationship between cancer and PD. Recent results identified several PD-associated proteins and factors mediating cancer development and cancer-associated factors affecting PD. Accumulating data point to the role of genetic traits, members of the synuclein family, neurotrophic factors, the ubiquitin–proteasome system, circulating melatonin, and transcription factors as mediators. Here, we present recent data about shared pathogenetic factors and mediators that might be involved in the association between these two diseases. We discuss how these factors, individually or in combination, may be involved in pathology, serve as links between PD and cancer, and affect the prevalence of these disorders. Identification of these factors and investigation of their mechanisms of action would lead to the discovery of new targets for the treatment of both diseases.

show abstract

“…A direct effect of CR on expression of macroautophagy-related genes has also been demonstrated recently in different tissues from old rats ( 36 ). Other macroautophagy regulators shown to be impacted by CR include the PI3K/AKT/MTOR and ERK1/2 MAPK signaling pathways ( 37 ), protein kinase CK2 ( 38 ), and the transcription factor TFEB ( 39 ). The regulatory effect of CR on macroautophagy involves, in part, the reversion of age-dependent changes in acetylation of important macroautophagy proteins ( 40 ).…”

mentioning

confidence: 99%

Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy

Jafari,

Macho-González,

Diaz

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Chaperone-mediated autophagy (CMA) is part of the mammalian cellular proteostasis network that ensures protein quality control, maintenance of proteome homeostasis, and proteome changes required for the adaptation to stress. Loss of proteostasis is one of the hallmarks of aging. CMA decreases with age in multiple rodent tissues and human cell types. A decrease in lysosomal levels of the lysosome-associated membrane protein type 2A (LAMP2A), the CMA receptor, has been identified as a main reason for declined CMA in aging. Here, we report constitutive activation of CMA with calorie restriction (CR), an intervention that extends healthspan, in old rodent livers and in an in vitro model of CR with cultured fibroblasts. We found that CR-mediated upregulation of CMA is due to improved stability of LAMP2A at the lysosome membrane. We also explore the translational value of our observations using calorie-restriction mimetics (CRMs), pharmacologically active substances that reproduce the biochemical and functional effects of CR. We show that acute treatment of old mice with CRMs also robustly activates CMA in several tissues and that this activation is required for the higher resistance to lipid dietary challenges conferred by treatment with CRMs. We conclude that part of the beneficial effects associated with CR/CRMs could be a consequence of the constitutive activation of CMA mediated by these interventions.

show abstract

TFEB is a central regulator of the aging process and age-related diseases

Cited by 11 publications

References 193 publications

Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks

Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks

Association between Parkinson’s Disease and Cancer: New Findings and Possible Mediators

Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy

Contact Info

Product

Resources

About