Aging-US: ALDH2 protects naturally aged mouse retina09-08-2021
Aging-US published a Special Collection on Eye Disease which included "ALDH2 protects naturally aged mouse retina via inhibiting oxidative stress-related apoptosis and enhancing unfolded protein response in endoplasmic reticulum" which reported that during the process of aging, the retina exhibits chronic oxidative stress damage.
These authors' preliminary experiment showed that acetaldehyde dehydrogenase 2 could alleviate retinal damage caused by OS. Retinal function and structure in vivo and in vitro were examined in aged ALDH2+ overexpression mice and ALDH2 agonist Alda1-treated aged mice.
Levels of ALDH2, endoplasmic reticulum stress, apoptosis and inflammatory cytokines were evaluated. Moreover, aged ALDH2+ overexpression mice and aged Alda1-treated mice exhibited better retinal function and structure. Increased expression of glucose-regulated protein 78 and ERS-related protein phosphorylated eukaryotic initiation factor 2 and decreased expression of apoptosis-related protein, including C/EBP homologous protein, caspase12 and caspase9, and retinal inflammatory cytokines were detected in the retina of aged ALDH2+ overexpression mice and aged Alda1-treated mice.
Dr. Tao Chen and Dr. Wei Ge said, "The aging process is characterized by a decline in systematic tissue function and the onset of serious of age-related disease."
Figure 11. The expression of apoptosis related proteins in aged ALDH2 overexpression and aged Alda1-treated mice. (A) A typical WB image of CHOP, caspase9 and caspase12 in aged ALDH2 overexpression mice; (B–D) The expression of CHOP, caspase9 and caspase12 in aged ALDH2 overexpression mice; (E) A typical WB picture of CHOP, caspase9 and caspase12 in aged Alda1-treated mice; (F–H) The expression of CHOP, caspase9 and caspase12 in aged Alda1-treated mice. All analyses were performed in duplicate. Values are presented as the mean ± SD, n = 4 mice per group. *P<0.05: aged (WT) and aged (ALDH2+) vs young (WT) or Aged (DMSO) and aged (Alda1) vs young; **P<0.01: aged (WT) and aged (ALDH2+) vs young (WT) or Aged (DMSO) and aged (Alda1) vs young; ***P<0.001: aged (WT) and aged (ALDH2+) vs young (WT) or Aged (DMSO) and aged (Alda1) vs young; #P<0.05: aged (ALDH2+) vs aged (WT) or aged (Alda1) vs aged (DMSO), ##P<0.01: aged (ALDH2+) vs aged (WT) or aged (Alda1) vs aged (DMSO).
However, it remained elusive that the potential mechanisms accounting for these phenomena and strategies to intervene to improve cell functions. Recently, the imbalance of protein homeostasis was proposed to be responsible for aging and age-related diseases.
Furthermore, eukaryotic translation initiation factor 2, a protein translation component, is the downstream of PERK. When endoplasmic reticulum stress happens, eIF2 is phosphorylated to slow down protein production and reduce the unfolded and misfolded proteins.
Nevertheless, the underlying mechanisms of UPRER related to aged retinal behaviour remain largely unclear, and effective therapies to intervene in aging-related injury to the retina by targeting the UPRER have not been developed. Mitochondrial aldehyde dehydrogenase 2 is essential for the catabolism of exogenous and endogenous toxic aldehydes associated with oxidative stress-induced lipid peroxidation and adducts with DNA, RNA and protein.
The Chen/Ge Research Team concluded in their Aging-US Research Output, "overexpression of ALDH2 and treatment with the ALDH2 agonist Alda1 in aging mice could both result in good retinal function and structural integrity via attenuating oxidative stress and apoptosis, and enhancing UPRER. Therefore, an increasing expression of ALDH2 could serve to preserve retinal function during the normal aging process or the onset of age-related retinal disease."
Full Text - https://www.aging-us.com/article/202325/text
Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.