Sigma and Aging

Published research to date related to Sigma proteins and Aging has been conducted with compounds not developed by Advantx Pharmaceuticals Inc. Our therapeutic candidate ADV127 for Aging is the first truly selective, pharmaceutical-grade compound in development targeting the Sigma-1 receptor with a clean molecule and unambiguous agonist activity, far superior in potency, selectivity, safety, and efficacy to all others tested to date.


Novel compound inhibits glycolysis, proteotoxicity, inflammation, and impairments in animal models of Alzheimer’s, Huntington’s, and stroke: Aging as a consequence of glycolysis

By Rachel Litke, Kun-Hyung Roh, Yonejung Yoon, Sindhu Vangeti, Irene Ramos-lopez, Husnu Kaniskan, Jian Jin, Christopher Kellner, and Charles Mobbs Excerpt from the article published in bioRxiv 2023.06.12, 544352; doi: Editor’s Highlights Abstract Alzheimer’s Disease (AD) and other age-related diseases are increasingly among the most devastating strains on public health systems as the population ages, yet […]

Sigma 1 receptor activation improves retinal structure and function in the RhoP23H/+ mouse model of autosomal dominant retinitis pigmentosa

By Shannon R. Barwick, Haiyan Xiao, David Wolff, Jing Wang, Elizabeth Perry, Brendan Marshall, and Sylvia B. Smith Extract from the article published in Experimental Eye Research, Volume 230, May 2023, 109462, ISSN 0014-4835, DOI: Editor’s Highlights Abstract Retinitis pigmentosa (RP) is a group of devastating inherited retinal diseases that leads to visual impairment and oftentimes complete blindness. Currently no […]

Antipsychotics function as epigenetic age regulators in human neuroblastoma cells

By Jianbin Du, Yutaka Nakachi, Ayaka Fujii, Shinya Fujii, Miki Bundo, and Kazuya Iwamoto Excerpt from the article published in Schizophrenia 8, 69, 29 August 2022. DOI: Editor’s Highlights Schizophrenia is proposed to be a syndrome of accelerated aging in the body, which is partly the cause of the shortened lifespan of patients with schizophrenia. […]

Adenosine A2A receptors control synaptic remodeling in the adult brain

By Xinli Xu, Rui O. Beleza, Francisco Q. Gonçalves, Sergio Valbuena, Sofia Alçada-Morais, Nélio Gonçalves, Joana Magalhães, João M. M. Rocha, Sofia Ferreira, Ana S. G. Figueira, Juan Lerma, Rodrigo A. Cunha, Ricardo J. Rodrigues, and Joana M. Marques Excerpt from the article published in Scientific Reports 12, 14690, 29 August 2022, DOI: Editor’s […]

Mitochondria-Associated Endoplasmic Reticulum Membranes: Inextricably Linked with Autophagy Process

By Chonghao Ji, Zhanwei Zhang, Zechuan Li, Xiao She, Xiaoya Wang, Binyang Li, Xin Xu, Dawei Song, and Dongjiao Zhang Excerpt from the article published in Oxidative Medicine and Cellular Longevity (Hindawi), Volume 2022, 23 Aug 2022, Article ID 7086807, DOI: Editor’s Highlights There is a growing body of evidence indicating Mitochondria-associated membranes (MAMs) act as […]

Activation of the sigma-1 receptor exerts cardioprotection in a rodent model of chronic heart failure by stimulation of angiogenesis

By Xin Zhao, Xin Liu, Xiuhuan Chen, Xueyu Han, Yazhou Sun, Yuhong Fo, Xiukun Wang, Chuan Qu, and Bo Yang Excerpt from the article published in Molecular Medicine volume 28, Article number: 87, 03 August 2022, DOI: Editor’s Highlights With the increase of global aging population, the incidence of Heart Failure (HF) has increased […]

PGRMC1 Regulates Cellular Senescence via Modulating FOXO1 Expression in Decidualizing Endometrial Stromal Cells

By Atsuya Tsuru, Mikihiro Yoshie, Junya Kojima, Ryo Yonekawa, Mana Azumi, Kazuya Kusama, Hirotaka Nishi, and Kazuhiro Tamura Excerpt from the article published in Biomolecules 2022, 12, 1046, 28 July 2022, DOI: Editor’s Highlights The differentiation of endometrial stromal cells (ESCs) into decidual cells is essential for the acquisition of endometrial receptivity for implantation and subsequent […]

Mitochondrial dysfunction in cell senescence and aging

By Satomi Miwa, Sonu Kashyap, Eduardo Chini, and Thomas von Zglinicki Excerpt from the article in Journal of Clinical Investigation 2022;132(13):e158447. Published July 1, 2022, DOI: Editor’s Highlights Mitochondrial dysfunction in aging tissues and senescent cells is a decrease in respiratory capacity per mitochondrion together with a decreased mitochondrial membrane potential (MMP) at steady […]

Proteostasis collapse is a driver of cell aging and death

By Mantu Santra, Ken A. Dill, and Adam M. R. de Graff Excerpt from the article published in PNAS, 116(44) 22173-22178, October 16, 2019, DOI: Editor’s Highlights Aging results from declining protein quality-control systems involved in protein synthesis, degradation, and chaperoning that normally protect the proteins in the cell’s proteome Proteostasis, the decline in protein […]

Protein lifetimes in aged brains reveal a proteostatic adaptation linking physiological aging to neurodegeneration

By Verena Kluever, Belisa Russo, Sunit Mandad, Nisha Hemandhar Kumar, Mihai Alevra, Alessandro Ori, Silvio O. Rizzoli, Henning Urlaub, Anja Schneider, and Eugenio F. Fornasiero Excerpt from the article published in Science Advances, 20 May 2022, Vol 8, Issue 20 DOI: 10.1126/sciadv.abn4437 Editor’s Highlights Physiologically aged brain has revealed only minor alterations in protein abundances in the aged […]

Aging is associated with increased brain iron through cortex-derived hepcidin expression

By Tatsuya Sato, Jason Solomon Shapiro, Hsiang-Chun Chang, Richard A Miller, and Hossein Ardehali Excerpt from the article published in eLife 11:e73456. DOI: Editor’s Highlights Iron is critical for normal cell function, but its excess can lead to cellular damage due to oxidative stress. Iron accumulates in the brain cortex with aging and that this […]

Cellular senescence links mitochondria-ER contacts and aging

By Dorian V. Ziegler, Nadine Martin, and David Bernard Excerpt from the article published in Communications Biology 4, 1323 (2021). DOI: Editor’s Highlights Endoplasmic reticulum (ER) and mitochondria constitute two key organelles involved in macromolecules synthesis and bioenergetics, but also in stress sensing and integration of cell fate signaling. ER and mitochondria interact with each other […]

Aging with Down Syndrome—Where Are We Now and Where Are We Going?

by Melissa J. Alldred, Alessandra C. Martini, David Patterson, James Hendrix, and Ann-Charlotte Granholm Excerpt from the article published in Journal of Clinical Medicine 10, no. 20: 4687. 13 October 2021 DOI: Abstract Down syndrome (DS) is a form of accelerated aging, and people with DS are highly prone to aging-related conditions that include vascular […]

The Unfolded Protein Response in Immune Cells as an Emerging Regulator of Neuroinflammation

By Dominique Fernández, Antonia Geisse, Jose Ignacio Bernales, Alonso Lira, and Fabiola Osorio Excerpt from the article published in Frontiers of Aging Neuroscience, 11 June 2021, Sec. Cellular and Molecular Mechanisms of Brain-aging, DOI: Editor’s Highlights Cells possess regulatory mechanisms that maintain proteostasis in conditions that overload the folding capacity of the organelle (a […]

Interorganelle communication, aging, and neurodegeneration

By Maja Petkovic, Caitlin E. O’Brien, and Yuh Nung Jan Excerpt from the article published in Genes & Dev. 2021. 35: 449-469 PMCID: PMC8015714 DOI: 10.1101/gad.346759.120 Editor’s Highlights Cellular organelles and their associated processes do not function in isolation, but within a robust cellular communication network—the cellular communicome—to maintain homeostasis.  Many proteins participate at multiple distinct contact sites between different […]

Targeting cellular senescence based on interorganelle communication, multilevel proteostasis, and metabolic control

By Maria Cavinato, Corina T. Madreiter-Sokolowski, Sabrina Büttner, Markus Schosserer, Werner Zwerschke, Sophia Wedel, Johannes Grillari, Wolfgang F. Graier, and Pidder Jansen-Dürr Excerpt from the article published in The FEBS Journal, 17 November 2020, DOI: Editor’s Highlights Aging is a complex process driving progressive decline of functionality and regenerative potential of tissues. During aging, […]

Sigma‐1 receptor protects against ferroptosis in hepatocellular carcinoma cells

By Tao Bai, Pengxu Lei, Hao Zhou, Ruopeng Liang, Rongtao Zhu, Weijie Wang, Lin Zhou, and Yuling Sun Excerpt from the article published in Journal of Cellular and Molecular Medicine 2019 Nov; 23(11): 7349–7359.  DOI: 10.1111/jcmm.14594 Editor’s Highlights Hepatocellular carcinoma (HCC) is a common type of cancer that is ranked sixth in prevalence and third in mortality worldwide. […]

Cardiac 11C-Donepezil Binding Increases With Age in Healthy Humans: Potentially Signifying Sigma-1 Receptor Upregulation

By Jacob Horsager, Tatyana D. Fedorova, Nathalie V.D. Berge, Mette W. Klinge, Karoline Knudsen, Allan K. Hansen, Aage K.O. Alstrup, Klaus Krogh, Lars Gormsen, and Per Borghammer Excerpt from the article published in Journal of Cardiovascular Pharmacology and Therapeutics. July 2019:365-370. doi: 10.1177/1074248419838509 Editor’s Highlights Sigma-1 receptors (S1Rs) are upregulated in the heart in response […]

Targeting the Endoplasmic Reticulum Unfolded Protein Response to Counteract the Oxidative Stress-Induced Endothelial Dysfunction

By Giuseppina Amodio, Ornella Moltedo, Raffaella Faraonio, and Paolo Remondelli Excerpt from the article published in Oxidative Medicine and Cellular Longevity, vol. 2018, Article ID 4946289, 13 pages, 14 Mar 2018. DOI: Editor’s Highlights Abstract In endothelial cells, the tight control of the redox environment is essential for the maintenance of vascular homeostasis. The […]