Part 2 of Eat broccoli sprouts for your eyes

I was a little bothered by an unreferenced statement in Eat broccoli sprouts for your eyes that:

“Once AGEs are formed, most are irreversible.”

I searched curated 2020 studies for “revers” and found that recent blog studies favored reversibility of epigenetic changes 12-to-2. Do they reflect my selection bias, or is there something different about AGEs?

Let’s start with this statement:

“Although AGEs are irreversible adducts and cross-links in our tissues, these can be removed through different proteolytic capacities:

  • The ubiquitin proteasome system (UPS) – Ubiquitin is a protein that when conjugated to a protein substrate can facilitate degradation of that substrate by the proteasome. Obsolete or damaged proteins are tagged with ubiquitin and these ubiquitinated substrates are degraded by the proteasome. Operates mainly on soluble substrates.
  • Autophagy – Can operate on insoluble substrates, including organelles such as mitochondria. Autophagy requires macromolecular assemblies and organelles to identify, sequester, and eventually degrade substrates via the lysosome.

Unfortunately, the function of both proteolytic pathways declines with extensive glycative stress and upon aging in many tissues, resulting in intracellular accumulation of protein aggregates (also glycated conjugates) and dysfunctional organelles. This thwarts strategies to lower AGEs accumulation by boosting proteolytic capacities.”

https://www.mdpi.com/2076-3921/9/11/1062/htm “Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy”


So humans can remove irreversible AGE epigenetic changes as long as the individual isn’t too stressed or old? Studies from 2008 to 2012 were cited for the above statement and graphic.

Citation 211 Sulforaphane delays diabetes-induced retinal photoreceptor cell degeneration (not freely available) 2020 findings were instructive:

“SF [sulforaphane] can delay photoreceptor degeneration in diabetes. The underlying mechanism is related to:

  • Inhibition of ER [endoplasmic reticulum] stress;
  • Inflammation; and
  • Txnip [thioredoxin-interacting protein] expression through activation of the AMPK [adenosine 5′-monophosphate (AMP)-activated protein kinase] pathway.

Function of the retina in diabetic [DM] mice as determined by ERG [electroretinography].”


This chart demonstrated that preventing diabetes’ retinal effects (non-diabetic control bar) was measurably better than trying to fix them. Are future choices of humans who give themselves this non-communicable disease also limited to addressing symptoms?

The AMPK pathway was mentioned in:

  1. Reversal of aging and immunosenescent trends with sulforaphane:”

    Dihydroxyvitamin D3 and sulforaphane are compounds that safely induce AMPK activation, and may have wide-ranging implications for both normal and pathological aging.”

  2. Part 2 of Reversal of aging and immunosenescent trends with sulforaphane:

    “NQO1 plays a key role in AMPK-induced cancer cell death through the CD38/cADPR/RyR/Ca2+/CaMKII signaling pathway. Expression of NQO1 is elevated by hypoxia / reoxygenation or inflammatory stresses through nuclear accumulation of the NQO1 transcription factor, Nrf2. Activation of the cytoprotective Nrf2 antioxidant pathway by sulforaphane protects immature neurons and astrocytes from death caused by exposure to combined hypoxia and glucose deprivation.”

This first example was vitamin D3’s separate yet connected signaling pathway that acts both additively and synergistically with broccoli sprout compound effects. Followed by signaling pathways becoming cascadingly activated from sulforaphane’s main effect, Nrf2 signaling pathway activation.


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