Talk:Glucosepane

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The comment(s) below were originally left at Talk:Glucosepane/Comments, and are posted here for posterity. Following several discussions in past years, these subpages are now deprecated. The comments may be irrelevant or outdated; if so, please feel free to remove this section.

The problem with this page is that it doesn't suggest anything about what to do about it. I want to live longer than 90 years, and I don't want the proteins in my skin cross-linked. Can I limit this by avoiding the same things that increase AGEs? What about PABA and DMAE? What about heavy exercise that causes perspiration, is it volatile and removed in perspiration? I have a more general question: Why doesn't the medical establishment and big pharma discuss and work on things like this? Tens of thousands of their customers die every day from aging.138.88.163.46 20:42, 23 October 2007 (UTC)Tom Schaefer[reply]

Last edited at 20:42, 23 October 2007 (UTC). Substituted at 16:24, 29 April 2016 (UTC)

Recent work from SENS.

Since about 2013, SENS has been funding relevant research, and there seem to have been some results. This isn't my field, so I'll proceed cautiously, but here's a timeline; much of this isn't published journal work, but rather SENS fanworks like "Fight Aging", but it should give a sense of how this happened. Notes not directly involving glucosepane are indented.

June 1999: An article in Bioorganic & Medicinal Chemistry first identifies glucosepane.
April 2002: Journal of Biological Chemistry publishes "Identification and Quantification of Major Maillard Cross-links in Human Serum Albumin and Lens Protein: EVIDENCE FOR GLUCOSEPANE AS THE DOMINANT COMPOUND", declaring that glucosepane "represents the dominant in vivo cross-link".

November 2005: Johns Hopkins Medicine reports "DRUG COMPOUND RESTORES YOUTH TO AGING ARTERIAL CELLS IN ELDERLY HYPERTENSIVES", citing unpublished data about alagebrium, noting that "Alagebrium has been under investigational study since 1999, originally as a treatment for hypertension. While clinical studies have demonstrated the drug's ability to loosen up stiff arteries, two larger studies in older people with hypertension have not shown significant results in lowering blood pressure."
2006: Alteon Inc. files its 10-K, describing its attempts to research and develop alagebrium.

2007: Aubrey de Grey writes in Ending Aging that "Glucosepane is the single most important contributor to the body's AGE burden known to date", and that it was first identified in 1999 (though the endnote isn't included in the preview).
2008: a chapter in Collagen: Structure and Mechanics says that "The significance of the major glycation cross-link, believed to be glucosepane, remains to be confirmed."

February 2009: Fight Aging reports that alagebrium/"ALT-711", despite promising results in rodents, did not show the same results in humans, as our AGEs are different from those in rodents.

October 2010: Fight Aging reports that SENS and InnoCentive offered a $20,000 prize (archived) for a proposal to break glucosepane links.
March 2013: Fight Aging reports that glucosepane has been identified as the primary AGE target in humans, and SENS is funding work on it, specifically in the SENS Research Foundation Laboratory in Cambridge, and David Spiegel's group at Yale.
January 2014: a review article in Clinical Chemistry and Laboratory Medicine says that "overall little biological and clinical information is available on glucosepane" and calls for more data.
October 2015: Spiegel's group publishes "Concise total synthesis of glucosepane" in Science; the abstract notes that "comprehensive biological investigations of this metabolite have been hindered by a scarcity of chemically homogeneous material available for study". (Fight Aging blurb, SENS blurb (archived), ACS Molecule of the Week.)
September 2017: SENS press release announces the formation of a research program dedicated to developing monoclonal antibodies against glucosepane, supervised by David Spiegel.
July 2018: Spiegel's group publishes "Identification of Glucosepane Cross-Link Breaking Enzymes" in Diabetes, describing "the first demonstration that glucosepane can be broken down enzymatically".
March 2019: SENS reports that Revel Pharmaceuticals has been founded (Jason Crawford, from Spiegel's team, is leading it).
April 2019: Spiegel's group publishes "Biocatalytic Reversal of Advanced Glycation End Product Modification" in ChemBioChem; from the abstract: "we show that MnmC, an enzyme involved in a bacterial tRNA‐modification pathway, is capable of reversing the AGEs carboxyethyl‐lysine (CEL) and carboxymethyl‐lysine (CML) back to their native lysine structure."
September 2020: Spiegel's group publishes "Generation and Characterization of Anti-Glucosepane Antibodies Enabling Direct Detection of Glucosepane in Retinal Tissue", describing "the development of the first polyclonal anti-glucosepane antibodies using a synthetic immunogen that contains the core bicyclic ring structure of glucosepane", which both "demonstrate[d] for the first time accumulation of glucosepane within the retinal pigment epithelium, Bruch’s membrane, and choroid: all regions of the eye impacted by age-related macular degeneration" and successfully imaged glucosepane. (SENS blurb, Lifespan.io blurb.)

I'll try to turn this into a proper edit on the page itself. grendel|khan 02:19, 14 October 2020 (UTC)[reply]