Published: 2:14 p.m. PST Aug 30, 2022 | Updated: 2:26 p.m. PST Sep 13, 2022
- NMN eliminates senescent cells and drops DNA damage by 50% in a human cell model for macular degeneration — an age-related eye disease.
- Treatment with NMN restores retina structure while reducing senescence in a mouse model for macular degeneration.
Our ability to visualize the fine details of our surroundings depends on a tiny patch of specialized neurons (photoreceptors) called the macula. With age, this region of the retina degenerates as our vision blurs, manifesting in a disease called macular degeneration. Now, scientists from Tongji University in China show that senescent cells — one of the hallmarks of aging — may contribute to macular degeneration.
As reported in Oxidative Medicine and Cellular Longevity, Ren and colleagues exposed human retina cells to a chemical called sodium iodate to establish a model for macular degeneration. They found that the experimentally-induced degenerated retina cells had increased levels of senescence, DNA damage, and harmful molecules called reactive oxygen species (ROS), all of which were reversed by treatment with nicotinamide mononucleotide (NMN). Furthermore, similar results were shown in mice, along with improvements in retina structure upon NMN treatment.
NMN Reduces Retina Damage
The retina is a layer of cells coating the back of the eye, vital for vision. Sodium iodate (NaIO3) is widely used to study age-related macular degeneration because it causes retinal degeneration. Upon exposure to NaIO3, Ren and colleagues showed that human retina cells displayed common characteristics of age-related retinal degeneration, including increased senescent cells, DNA damage, and excessive levels of ROS. By treating the degenerated retina cells with NMN, the percentage of senescent cells dropped, DNA damage was reduced by 50%, and ROS levels were suppressed.
(Ren et al., 2022 | Oxid. Med. Cell. Longev.) NMN Reduces Senescence in Degenerated Human Retina Cells. Relative to normal (control) retina cells, degenerated retina cells (NaIO3 1 mM) have increased senescent cells (β-gal), DNA damage (γ-H2AX), and reactive oxygen species (cytosolic ROS), all of which are lowered by NMN (NMN + NaIO3 1 mM).
One of the hallmarks of aging is a phenomenon known as senescence, whereby normal cells become senescent in response to cellular stressors like DNA damage and excessive ROS. Excessive accumulation of senescent cells stimulates inflammation and promotes the onset of multiple age-related diseases, including macular degeneration.
To paint a more physiological picture of NMN’s effect on retinal degeneration, Ren and colleagues injected mice with NaIO3 and examined their retinas. They found that NaIO3 induced structural changes in the mouse retinas and increased senescence. However, treating the NaIO3-exposed mice with NMN mitigated the structural changes and prevented the propagation of senescent cells.
(Ren et al., 2022 | Oxid. Med. Cell. Longev.) NMN Prevents Degenerated Mouse Retina Structural Changes. Staining of proteins (green, ZO-1) in the retina shows that NaIO3 (10 mg/kg) induces structural alterations relative to normal retinas (control), which is partially reversed by NMN (NMN + 10 mg/kg). NMN also restores NAD+ levels.
The findings of Ren and colleagues suggest that NMN can reverse aspects of retinal degeneration by boosting nicotinamide adenine dinucleotide (NAD+). NAD+ is an important molecule involved in energy metabolism, known to fuel enzymes capable of repairing DNA and reducing ROS. NAD+ content decreases with aging in various tissues including the retina. However, the Shanghai-based researchers showed that NAD+ levels were restored with NMN in their mouse model for macular degeneration.
Can NMN Prevent Age-Related Blindness?
According to the National Eye Institute, macular degeneration can potentially lead to partial blindness. However, by slowing down the degeneration of the retina with supplements, it may be possible to prevent vision acuity loss. These supplements include vitamins and minerals like zinc, vitamin E, and vitamin C. Now, can NMN be added to this list?
NMN has previously been shown to mitigate macular degeneration and protect against retinal detachment in animal models. Additionally, an enzyme important for NAD+ synthesis is depleted in degenerated rodent retinas and grape seed extract has been shown to reverse retina aging by activating another NAD+-related enzyme in mice. This means that the enzymes necessary to generate NAD+ seem to be lost during retinal aging. Since NMN can bypass these enzymes, NMN can potentially protect against retinal aging. Overall, while human studies are needed, these animal studies make NMN a promising candidate for the slowing of macular degeneration and perhaps preventing partial blindness.
Ren C, Hu C, Wu Y, Li T, Zou A, Yu D, Shen T, Cai W, Yu J. Nicotinamide Mononucleotide Ameliorates Cellular Senescence and Inflammation Caused by Sodium Iodate in RPE. Oxid Med Cell Longev. 2022 Jul 18;2022:5961123. doi: 10.1155/2022/5961123. PMID: 35898618; PMCID: PMC9313989.