Verapamil extends lifespan in by inhibiting calcineurin activity and promoting autophagy.

08:00 EDT 24th March 2020 | BioPortfolio

Summary of "Verapamil extends lifespan in by inhibiting calcineurin activity and promoting autophagy."

Previous evidence has revealed that increase in intracellular levels of calcium promotes cellular senescence. However, whether calcium channel blockers (CCBs) can slow aging and extend lifespan is still unknown. In this study, we showed that verapamil, an L-type calcium channel blocker, extended the () lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in as reflected by several age-related physiological parameters, including locomotion, thrashing, age-associated vulval integrity, and osmotic stress resistance. We also found that verapamil acted on the α1 subunit of an L-type calcium channel in . Moreover, verapamil extended worm lifespan by inhibiting calcineurin activity. Furthermore, verapamil significantly promoted autophagy as reflected by the expression levels of LGG-1/LC3 and the mRNA levels of autophagy-related genes. In addition, verapamil could not further induce autophagy when , calcineurin gene, was knocked down, indicating that verapamil-induced lifespan extension is mediated via promoting autophagy processes downstream of calcineurin. In summary, our study provided mechanistic insights into the anti-aging effect of verapamil in .


Journal Details

This article was published in the following journal.

Name: Aging
ISSN: 1945-4589


DeepDyve research library

PubMed Articles [13778 Associated PubMed Articles listed on BioPortfolio]

Effect of verapamil on the pharmacokinetics of hydroxycamptothecin and its potential mechanism.

Hydroxycamptothecin (HCPT) has antitumor activity in various cancers, but its poor bioavailability and efflux limit its clinical application. Verapamil has been demonstrated to improve the bioavailabi...

Longevity in response to lowered insulin signaling requires glycine N-methyltransferase-dependent spermidine production.

Reduced insulin/IGF signaling (IIS) extends lifespan in multiple organisms. Different processes in different tissues mediate this lifespan extension, with a set of interplays that remain unclear. We h...

Inhibition of autophagy improves resistance and enhances sensitivity of gastric cancer cells to cisplatin.

Autophagy plays critical roles in tumorigenesis, while effects of autophagy on chemoresistance of cancer cells had great disparity. This study aims to explore the impacts of autophagy on the sensitivi...

Impact of NF-κB pathway on the apoptosis-inflammation-autophagy crosstalk in human degenerative nucleus pulposus cells.

The NF-κB pathway has been reported to play a very important role in the process of intervertebral disc degeneration (IVDD). Our results demonstrated that knockdown of NF-κB with P65-siRNA can signi...

Insulin impedes osteogenesis of BMSCs by inhibiting autophagy and promoting premature senescence via the TGF-β1 pathway.

The dysfunction of bone marrow stromal cells (BMSCs) may be a core factor in Type 2 diabetes mellitus (T2DM) associated osteoporosis. However, the underlying mechanism is not well understood. Here, we...

Clinical Trials [5056 Associated Clinical Trials listed on BioPortfolio]

Pharmacotherapy of Treatment-Resistant Mania

Verapamil has been found in some but not all studies to have antimanic activity. Therefore, we investigated the use of verapamil, alone or as an adjunctive treatment, in manic patients wh...

Bioequivalence Study Of Verapamil

The purpose of this study is to demonstrate bioequivalence of single doses of two verapamil formulations

Verapamil and Catamenial Epilepsy

One in 3 epilepsy patients have refractory seizures. This drug resistance is likely related to the over expression of multidrug resistance proteins (MDR). Progesterone is a known inhibitor...

Study to Evaluate the Value of the Follow-up of CALCIneurin Activity to MOdulate Calcineurin Inhibitors-induced Immunosuppression in Lung Transplantation

The study is an interventional, multicentre, prospective, randomized, controlled, single-blind, comparative trial of two processes for adjusting the inhibitor of calcineurin (CNI) dosage i...

Drug-Drug Interaction Between Colchicine and Verapamil ER

Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Verapamil hydrochloride is a potent inhibitor of cytochrome P450 (CYP) 3A4 and P-gp. This study ...

Medical and Biotech [MESH] Definitions

Compounds that inhibit or block the PHOSPHATASE activity of CALCINEURIN.

A CALCIUM and CALMODULIN-dependent serine/threonine protein phosphatase that is composed of the calcineurin A catalytic subunit and the calcineurin B regulatory subunit. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including HISTONES; MYOSIN LIGHT CHAIN; and the regulatory subunits of CAMP-DEPENDENT PROTEIN KINASES. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes.

Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.

Proteins and enzymes that function, often as components of MULTIPROTEIN COMPLEXES, to assemble AUTOPHAGOSOMES and carry out AUTOPHAGY.

An autophagy related protein that is similar to UBIQUITIN-ACTIVATING ENZYME E1. It functions in CYTOPLASM to VACUOLE transport (Cvt) and AUTOPHAGY by activating ATG12 PROTEIN for its conjugation with ATG5 PROTEIN, as well as the conjugation of ATG8 FAMILY PROTEINS with phosphatidylethanolamine for ATG8 association to Cvt vesicles and AUTOPHAGOSOME membranes. It is also required for the nitrogen starvation response in yeast, MITOPHAGY; and autophagic cell death induced by CASPASE 8 inhibition.

Quick Search

DeepDyve research library

Relevant Topics

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...

Searches Linking to this Article