Many people are somewhat familiar with the word “senescence” and equate the term as being synonymous with aging. After all, the root of the word is “sen-” meaning old and is also the root of the word “senile” which of course means characteristic of old age.

But when biologists speak about cellular senescence, they do not exactly mean aging the way people usually think about this process. Depending on the type of tissue, cells in your body live varying lengths of time. White blood cells have a lifespan of about 13 days, as compared to the 120 days a red blood cell lives. Fat cells live about eight years and intestinal cells (excluding the lining) live nearly 16 years.

When body cells reach the end of their natural life, they die a preprogramed death via a process called apoptosis (say “a-pop-TOE-sis”) which is designed not to damage any cells nearby. Or perhaps a cell is young or in mid-life and is damaged in some way. Many times this damage can be repaired and the cell resumes its normal function. If the damage is too severe, again the cell undergoes apoptosis and is destroyed.

Normally, cells undergo constant division, both to replace cells that have died and also to aid in repair, as in growing new skin cells to close a wound. Sometimes, when cellular DNA is damaged, these cells become cancerous and get catapulted into unchecked proliferation.

Understanding Cellular Senescence

The other way cells respond to damage that is not so severe as to trigger apoptosis is to become senescent. This means that instead of spiralling into out-of-control proliferation, they simply stop dividing and the normal cell cycle ends. Many scientists believe that this ability to go into a senescent state is the body’s way of trying to prevent these damaged cells from becoming cancerous.

Although these senescent cells are not actively dividing, they are not by any means dead. The senescent cells are still very much metabolically active, secreting an array of proteins and other molecules referred to as the SASP (senescence-associated secretory phenotype) which can cause inflammation. In this way, the senescent cells can signal immune cells to come in to help clean up damage and to help with tissue repair. So far, this looks like a good thing.

But even though the SASP does assist in tissue repair, some of the proteins and molecules which may up this array can have detrimental effects. As you age, senescent cells begin to accumulate in the body, including the brain. These senescent cells all produce the SASP inflammatory molecules and proteins, which can actually accelerate aging itself and worsen age-related conditions such as heart disease and Alzheimer’s. Plus ongoing exposure to the SASP can actually induce senescence in otherwise healthy cells.

Clearing Senescent Cells From The Body

What if these senescent cells could be cleared from the body, along with the toxic inflammatory SASP proteins and molecules they produce? It’s already been shown that in a mouse model of neurodegenerative disease, the clearance of senescent cells has been shown to improve brain function in these animals.

But what was not known is this: could the clearance of senescent cells from the body help to alleviate the brain aging and cognitive decline that comes with normal aging? Recent research spearheaded by scientists at the Mayo Clinic’s Robert and Arlene Kogod Center on Aging published in the January 21, 2021 issue of the journal Aging Cell, attempted to answer this question.

The researchers again turned to a mouse model in their attempt to answer this question. The team used transgenic mice. These mice are specifically bred to be part of medical research and have “foreign” DNA inserted into the nucleus of a fertilized mouse egg. When the mouse develops, the foreign DNA becomes part of every cell. These specially bred mice enabled the team to use a drug that selectively kills cells that express P16ink4a, a protein involved in cell cycle regulation and that slows cell division.

As organisms get older, the expression of the P16ink4a protein increases. This helps the body to reduce the proliferation of stem cells which reduces cancer risk but at the same time makes the body susceptible to the effects of the SASP proteins and other molecules these senescent cells produce. Because this approach could not guarantee the destruction of all senescent cells, the researchers also used a combination drug cocktail to target the remaining senescent cells in the mice. The researchers used several cohorts of aged mice (25 to 29 months) as well as a younger group as a comparison.

The results were quite clear: the removal of senescent cells in the bodies and brains of the aged mice resulted in the alleviation of age-related cognitive impairment, specifically spatial memory dysfunction. The results also showed a reduction in markers of senescence in the neurons of the hippocampus, a part of the brain specifically associated with memory and cognition and which is subject to progressive deterioration with age.

The clearance of the senescent cells also significantly reduced markers of brain inflammation which has been clearly associated with age-related cognitive impairment. While the authors stress that it is still not completely clear exactly how cellular senescence affects brain aging, the results of their study definitively show that therapies directed at clearing senescent cells provide a promising approach to rejuvenation of the aging brain as well as the improvement of memory in older people.

NAD And Cellular Senescence

As we have reported in prior articles, NAD (nicotinamide adenine dinucleotide) which acts in the body as an important coenzyme or cofactor, and naturally declines with age, has shown very promising results in the anti-aging arena, including the area of cellular senescence. Research from the University of Queensland, Australia, published in the February 18, 2020 issue of Cell Reports, showed that relatively low doses of NMN were effective in restoring egg quality in aged mice. Although the initial research was carried out in mice, the researchers are quite optimistic about the promise these agents have in the treatment of human fertility,

Researchers have conclusively shown in mouse models that treatment with NAD bestows powerful anti-aging effects on the neurovascular system, including improved cognitive performance. Furthermore, treatment of vascular cells from aged rats (biological age of 24-month-old mice corresponds to that of approximately 60-year-old humans) which were treated with NMN for five days showed a restoration of youthful NAD levels and return of mitochondrial function. We have also discussed elsewhere that NAD plays a crucial role in the optimal functioning of the sirtuins (say “sir-TWO-ins”), a family of proteins known as the longevity genes, which regulate cellular aging.

Even though practices such as caloric restriction and fasting have been shown to increase NAD levels, taking a high-quality NAD+ supplement daily is the most reliable, practical, and effective way to be certain you are meeting your NAD needs.

You can find complete information on all of our quality NAD+ supplements here, including NAD+ as well as its precursor NMN. Taken daily, NAD+ supplementation will increase your levels of this powerful coenzyme and give you the very best protection against the effects of the aging process, including aging’s detrimental effects on your cognitive health.

References:

1. Ogrodnik, M., Evans, S.A., Fielder, E., Victorelli, S., Kruger, P., Salmonowicz, H., Weigand, B.M., Patel, A.D., Pirtskhalava, T., Inman, C.L., Johnson, K.O., Dickinson, S.L., Rocha, A., Schafer, M.J., Zhu, Y., Allison, D.B., von Zglinicki, T., LeBrasseur, N.K., Tchkonia, T., Neretti, N., Passos, J.F., Kirkland, J.L. and Jurk, D. (2021), Whole‐body senescent cell clearance alleviates age‐related brain inflammation and cognitive impairment in mice. Aging Cell, 20: e13296. https://doi.org/10.1111/acel.13296.

2. Bertoldo et al. NAD Repletion Rescues Female Fertility during Reproductive Aging. Cell Reports, 2020; 30 (6): 1670 DOI: 10.1016/j.celrep.2020.01.058
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3. Tarantini S & Valcarcel-Ares MN et al. Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biol. 2019 Jun;24:101192. doi: 10.1016/j.redox.2019.101192. Epub 2019 Apr 10. PMID: 31015147; PMCID: PMC6477631.

4. Hou Y, Lautrup S, Cordonnier S, et al. NAD+ addition normalizes Alzheimer’s features. Proceedings of the National Academy of Sciences Feb 2018, 115 (8) E1876-E1885; DOI:10.1073/pnas.1718819115.

5. Kiss T, Giles C, Tarantini S. et al. Nicotinamide mononucleotide (NMN) supplementation promotes anti‐aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti‐atherogenic effects. FASEB Journal 18 April 2020 https://doi.org/10.1096/fasebj.2020.34.s1.04769.