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Stem UP

Reversing aging is no longer sci-fi

Since ancient times, humans have always dreamed of having smooth, supple skin, being quick-witted and youthful even at the age of 80-90. However, aging often comes with a deterioration in physical appearance and health, along with many diseases such as cardiovascular disease, diabetes, and neurological degeneration such as Alzheimer’s and Parkinson’s, and cancer. Today, with the remarkable progress of science, reversing aging is no longer just a thing of science fiction movies.

NMN rejuvenates Stem Cells and Mitochondria by activating the longevity proteins (Sirtuins). Nicotinamide Mononucleotide supplementation improves mitochondrial dysfunction and rescues cellular senescence by the NAD+/Sirt3 pathway in Mesenchymal Stem Cells.

Notably, sirtuins are critical to repairing and maintaining the integrity of our genetic blueprints (DNA), which drive the majority of age-related diseases when compromised. However, sirtuins require NAD+ for activation. Thus, NAD+ precursors like NMN are prime candidates to turn up sirtuin’s health-boosting effects.

NMN’s ability to enhance mitochondrial function and decrease stem cell senescence through Sirt3 regulation demonstrates that NAD+ precursors could restore the therapeutic potential of stem cells and delay aging features by activating sirtuins.

As we age, our skin undergoes several changes. One of the most noticeable changes is the disturbance in skin pigmentation, which causes age spots or hyperpigmentation. Pigmentation is controlled by melanocytes, specialized cells that produce the pigment melanin. Melanin protects the skin from the damaging effects of ultraviolet (UV) radiation, which is one of the leading causes of skin aging.

However, with age, the number of melanocytes in the skin decreases, and the remaining melanocytes become less effective at producing melanin. This can lead to uneven pigmentation and the formation of age spots. Additionally, UV exposure can cause melanocytes to cluster together and produce too much melanin, resulting in dark patches on the skin.

NMN has been shown to improve the evenness of skin pigmentation in mice by increasing the number and function of melanocytes. In addition, NMN has been shown to protect against UV-induced skin damage and improve wound healing in mice. Boosting NAD+ levels with supplements like NMN can promote skin cell health during aging.

One of the most devastating age-related diseases is Alzheimer’s disease, which takes away our memories. NMN is claimed to improve cognition in rodents with Alzheimer’s, reduce brain plaques, and prevent neurodegeneration in Alzheimer’s mouse models. Although Alzheimer’s disease is an end-stage disease, many older adults also suffer from cognitive impairments such as the inability to learn, remember, and think properly.

NMN has also been shown to prevent age-related cognitive impairments in mice. These cognitive impairments are sometimes associated with depression, which NMN has also been shown to alleviate in mice.

As we age, our blood vessels become dysfunctional, leading to impaired blood flow to our brain and resulting in cognitive impairments. As reported in research, NMN can increase blood flow to the brain and improve cognitive function in mice. When the blood vessels in our brain become clogged, we can have a stroke, which damages our brain tissue. Research indicated that NMN can also delay stroke onset, prevent stroke damage, and improve cognition and mitochondrial health after stroke in rodents.

Also, it has been demonstrated that several plant compounds stimulate the division of neural progenitor and neural stem cells as well as neurogenesis, hence boosting brain regeneration and fostering recovery. Astragalosides from astragalus root, proanthocyanidins from grape seeds, and fucoidan from brown algae are examples of such herbal compounds. Yet, animal studies have shown that spirulina algae or the lingzhi fungus also have positive effects.

As we age, our heart becomes increasingly susceptible to irregular beats, which can lead to devastating outcomes such as heart failure. Research on animals indicated that NMN is able to protect against heart failure in mice. 

Unlike other tissues, heart tissue is not known to regenerate and is prone to scarring (fibrosis) after damage, which can lead to heart dysfunction. It also requires large amounts of energy to beat constantly and efficiently, and healthy mitochondria play a crucial role in providing this energy. NMN has been shown to improve heart metabolism, protect against heart failure, and rejuvenate mitochondria.

The heart is a vital part of the cardiovascular system, pumping oxygenated blood to our organs. When the blood vessels surrounding the heart become clogged, the cells nearby can become damaged and die due to a lack of oxygen, resulting in ischemia and often leading to heart attacks. NMN has been shown to protect the heart from ischemic injury in mice. 

Boosting NAD+ levels with NMN can protect the heart and improve cardiac function. In mice, NAD+ boosters have replenished NAD+ levels in the heart and prevented injuries caused by a lack of blood flow. Other studies have shown that NAD+ boosters can protect mice from abnormal heart enlargement.

Our blood vessels transport vital nutrients to all our cells, and as we age, they become more rigid and susceptible to blockages, which can lead to heart attacks or strokes. Reversing vascular aging by restoring blood vessel function in mice is also another effect of NMN on maintaining cardiovascular health.

Senescent cells, which accumulate with aging and contribute to the aging of many organ systems, including the vascular system, contribute to this process. In mice, NMN stops blood vessel aging by reducing senescent cells, leading to the alleviation of hypertension. Senescent cells promote inflammation, which underlies nearly every age-related disease, and NMN has been shown to reverse blood vessel dysfunction by reducing inflammation in mice.

The mitigation of ischemic/reperfusion damage may be supported by vitamin E, coenzyme Q10, and the rutin flavonoid, reducing the deteriorating effect of oxidative stress and pro-inflammatory cytokines.

Vascular wall stem cells and cardiac stem cells could be activated by fucoidan (scientifically known as endothelial and cardiac progenitors). Their respective percentages climbed by 70% and 25%.

When our livers are injured, whether, from chronic alcohol use or the buildup of reactive oxygen species, it can result in scarring or fibrosis. This excessive scarring can lead to life-threatening diseases such as liver cancer and cirrhosis, and currently, there are no effective therapeutic options to prevent it.

However, a recent study published in Free Radical Biology and Medicine by Deng and colleagues has shown promising results. Injecting mice with nicotinamide mononucleotide (NMN) prevented liver fibrosis by inhibiting gene activity that typically promotes liver fibrosis. Additionally, NMN promoted the presence of the protein 15-PGDH, which reduced the levels of PGE2, a lipid that drives liver fibrosis.

Wakino and colleagues investigated the effect of NMN on urine protein levels, which are commonly associated with kidney damage and impaired filtration. To examine this, the research team established a model for glomerulosclerosis by injecting mice with a chemotherapy drug called adriamycin that causes kidney damage. The mice modeling kidney disease had significantly increased levels of urine protein. However, treating these mice with NMN reduced urine protein levels, suggesting a reduction in kidney damage and corrected protein filtration.

Researchers led by Dr. Hongxin Wei investigated the effects of NMN on levels of the proteins p16 and p21, which are associated with aging in mice. These proteins are linked to cell proliferation cessation during senescence and DNA damage accumulation, respectively. The research team found that NMN decreased the levels of both p16 and p21 in mouse lungs. This suggests that NMN can alleviate lung tissue senescence and protect it from aging.

NMN has been demonstrated to increase the number of mitochondria in the livers of obese mice, which may provide protection against obesity. NMN has the potential to aid overweight individuals in burning fat by encouraging the breakdown of fats. In addition, NMN has been shown to enhance the metabolism and health of mice born to obese mothers and the oocyte quality of obese mice.

NMN has been demonstrated to repair mitochondrial dysfunction related to macular degeneration in mice, which is a condition related to age that results in the degeneration of the retina’s central portion, responsible for clear vision. Severe cases of macular degeneration can result in blindness.

Inflammation and dryness are common age-related issues in the eyes. NMN has been shown to decrease inflammation and increase oil production in mice, which could help in treating dry eyes. Moreover, NMN has been found to reduce cell death and wound size after an eye injury.

As we age, our muscles lose their ability to regenerate and grow, leading to an age-related decline in muscle strength and size, a condition called sarcopenia. One of NMN’s transporters has been shown to increase strength and physical endurance in mice. In addition, NMN improves muscle strength and performance in older men and enhances oxygen utilization and exercise endurance in middle-aged runners.

NMN has been shown to improve bone density and reduce the risk of fractures in patients with glucocorticoid-induced osteoporosis by stimulating bone formation through the activation of the protein SIRT1.

Additionally, NMN has been found to increase the number and activity of bone-forming cells called osteoblasts, while reducing the number of bone-resorbing cells called osteoclasts, ultimately leading to an increase in bone mass and strength. These findings suggest that NMN could be a promising therapeutic option for patients with glucocorticoid-induced osteoporosis.

As women age, they experience a decline in the oocyte (egg) quality, which can lead to fertility problems. However, studies have shown that NMN can improve the age-related decline in oocyte quality and number, as well as female fertility in mice. Additionally, NMN has been found to protect oocytes from toxins in pigs, suggesting a potential benefit for women’s reproductive health.

As men get older, their ability to produce sperm, known as spermatogenesis, declines. Research conducted on mice suggests that the reduction in sperm production occurs due to the depletion of NAD+ levels that accompany aging. This has led some experts to suggest that NMN supplementation may improve low sperm counts in aging men by restoring NAD+ levels. Moreover, NMN has been shown to have positive effects that may counteract the negative effects of obesity on sperm quality.

As adults get older the immune system declines, and people get ill more easily. Recent studies have suggested that NAD+ levels play an important role in regulating inflammation and cell survival during the immune response and aging. The study underscored the therapeutic potential of NAD+ for immune dysfunction

There is emerging evidence that NMN may have a beneficial effect on allergies by reducing the release of histamine and IL-6 from mast cells in mice, which are involved in the body’s immune response to allergens (2). Histamine is a chemical compound released by immune cells in response to allergens and is responsible for the symptoms of allergies such as itching, sneezing, and congestion. IL-6 is a proinflammatory cytokine that is also involved in the immune response to allergens. By reducing the release of these proinflammatory proteins, NMN may help to alleviate the symptoms of allergies. However, more research is needed to determine the exact mechanisms by which NMN affects the immune system and whether it can be used as a treatment for allergies in humans.

The Basics

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3 fundamental causes of Aging

  • Shortening of Telomeres: Shortening of telomeres is considered a prognostic factor for aging and age-related diseases. Several studies have shown that protecting telomeres can help prevent age-related diseases, including cardiovascular disease, diabetes, and cancer.
  • Cellular Energy Depletion: In the aging process, NAD+ concentration in cells gradually decreases over time, contributing to the aging process and age-related diseases, and it is related to the decrease of cellular energy production.
  • Decline in Stem Cells: As we age, the number of stem cells decreases, reducing their ability to self-repair and leading to aging. They become less efficient in regenerating and repairing tissues and organs in the body, leading to reduced overall function and health.

NMN and anti-aging

NMN, or nicotinamide mononucleotide, is a molecule that has gained interest in anti-aging research due to its potential ability to boost levels of NAD+. This coenzyme plays a critical role in cellular metabolism and energy production. NAD+ levels decline as we age, which is believed to contribute to many age-related health problems. Supplementing with NMN increases NAD+ levels and promotes cellular health, potentially slowing the aging process.

One way NMN is thought to work is by activating the sirtuin Gene, a family of enzymes that play a role in regulating cellular function, including DNA repair, inflammation, and metabolism. Sirtuins have been linked to increased lifespan in several animal studies. According to the results of clinical trials of human studies, boosting sirtuin activity through NMN supplementation could lead to similar benefits in humans.

While the research on NMN and anti-aging is still in its early stages, there is growing evidence to suggest that NMN may have a range of health benefits beyond just anti-aging, including improved metabolic function, increased exercise endurance, and protection against age-related diseases.