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Restoring NAD+ is Vital For Healthy Aging

Emerging evidence implicates that elevation of NAD⁺ levels may slow or even reverse the aspects of aging and also delay the progression of age-related diseases.” (1)

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Increase NAD⁺ With Advanced 3-in-1 NAD⁺ Precursor

NAD⁺ Complete is a powerful 3-in-1 NAD⁺ booster with NAD⁺, NMN & NR. NMN & NR are precursors to NAD⁺, and each one utilizes different pathways for uptake in the body. The most effective protocol to increase NAD⁺ is through targeting all of these pathways.

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Energize NAD⁺ and Minimize NAD⁺ Consuming CD38

NAD⁺ Energizer is formulated to increase NAD⁺ levels and fuel your mitochondria, the powerhouse of your cells. This powerful combination of supplements also boosts sirtuins, while reducing the amount of circulating CD38 which consumes NAD⁺.

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Defend Existing NAD⁺ Pool By Minimizing Inflammation

NAD⁺ Defender is a unique combination of supplements formulated to reduce systemic inflammation to minimize NAD⁺ consumption.It prevents cellular senescence, slows age-related DNA methylation, & increases NAMPT, which is responsible for the conversion of nicotinamide to NAD⁺.

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Activate NAD⁺ Production & Destroy Senescent Cells

NAD⁺ Activator is specially formulated with the most powerful senolytics to eliminate senescent cells that increase inflammation and consume NAD⁺. It also contains AMPK activators to increase NAD⁺ production inside cells and throughout the body.

INFLAMMATION DRIVES AGING

“Age-associated chronic inflammation is characterized by unresolved and uncontrolled inflammation with multivariable low-grade, chronic and systemic responses that exacerbate the aging process and age-related chronic diseases.” (2)
Acute, or short-term inflammation is your body’s first line of defense against harmful agents, pathogens, allergens and toxins. It’s a normal process that ideally results in a resolution of the issues, while restoring the body to homeostasis.
If this short-term inflammatory response is unable to resolve the issue, then more defense mechanisms are activated and this can lead to a long-term unresolved immune state known as chronic inflammation.

Inflammation and NAD+ Decline

Chronic inflammation, often referred to as “inflammaging,” is a hallmark of aging. This persistent, low-grade inflammation contributes to the decline in NAD+ levels through multiple pathways.

Role of Inflammation in NAD+ Metabolism

Inflammation triggers the activation of immune cells, which express high levels of CD38. The increased activity of CD38 in these cells leads to accelerated NAD+ degradation. Moreover, inflammatory cytokines, such as TNF-α and IL-6, can upregulate the expression of CD38, further amplifying NAD+ consumption.

Inflammation also impacts the synthesis of NAD+. During chronic inflammatory states, the body’s ability to produce NAD+ through the de novo synthesis pathway is impaired. This pathway, which converts tryptophan into NAD+, is downregulated in the presence of inflammatory signals, leading to reduced NAD+ biosynthesis.

Mechanism of CD38-Induced NAD+ Decline

CD38 is an NAD+-consuming enzyme protein expressed on the surface of many immune cells, including macrophages and lymphocytes. With age, CD38 expression increases, leading to higher NAD+ consumption. This activity diminishes NAD+ availability, impairing functions that rely on this coenzyme, such as mitochondrial function, DNA repair, and cellular energy production.
CD38 also influences other NAD+-consuming enzymes, such as sirtuins and PARPs (poly ADP-ribose polymerases), further driving NAD+ depletion and promoting cellular aging.

NAD⁺, INFLAMMATION, and CD38

In aging, declining NAD⁺levels are associated with increased accumulation of proinflammatory M1-like resident macrophages in the liver and fat, which are characterized by increased expression of CD38.(3)
Thisresearchreview by Dr. Sinclair found increased CD38 responsible for the lower NAD⁺levels as we age.

“Furthermore, this decline in NAD⁺ levels is now known to affect multiple age-dependent cellular processes, including DNA repair, oxidative stress and immune cell function.” (3)

“Furthermore, this decline in NAD⁺ levels is now known to affect multiple age-dependent cellular processes, including DNA repair, oxidative stress and immune cell function.” (3)
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Senescence Speeds Aging Mechanisms

Senescent cells, sometimes called “zombie” cells, are minimally functional. However, they secrete damaging and inflammatory cytokines to surrounding tissues which can cause further damage and accelerate NAD+ depletion and aging.

Senescence Drives Aging

“The number of senescent cells increases with age, and senescent cells are present at sites of age-related pathology.” (4)
Senescence, the process by which cells irreversibly stop dividing and enter a state of permanent growth arrest, accelerate the aging process as these cells accumulate in tissues. While this mechanism initially acts as a protective measure against mutated replication and tissue damage, its accumulation over time leads to cumulative effects that impair cellular function.

Senescence and NAD+ Decline

Senescent cells are metabolically active and exhibit a pro-inflammatory secretory phenotype, known as the senescence-associated secretory phenotype (SASP). This phenotype includes the secretion of inflammatory cytokines, chemokines, and proteases, which contribute to a chronic inflammatory state and further promote tissue aging. (4)

Role of Senescence in NAD+ Metabolism

Senescent cells consume a considerable amount of NAD+ to sustain their altered metabolic state and maintain their secretory functions. This increased NAD+ demand, coupled with the cells’ impaired ability to produce NAD+, leads to a net decline in NAD+ levels. Additionally, the inflammatory environment created by SASP factors upregulates CD38 expression, an enzyme that degrades NAD+, further exacerbating NAD+ depletion. (5)

Mechanisms of Senescence-Induced NAD+ Decline

CD38, highly expressed on the surface of senescent cells, further accelerates the decline of NAD+ levels. As CD38 activity increases, more NAD+ is broken down into nicotinamide and ADP-ribose. This depletion of NAD+ impairs cellular processes such as DNA repair, mitochondrial function, and energy metabolism.
Furthermore, senescent cells contribute to mitochondrial dysfunction, which diminishes the efficiency of NAD+ production and increases its utilization in repair processes. The resulting imbalance accelerates the decline in NAD+ levels, leading to reduced cellular resilience and function.

Interventions Targeting Senescent Cells

Senolytics, compounds designed to selectively eliminate senescent cells, have shown promise in preclinical studies. By reducing the burden of senescent cells, senolytics can mitigate inflammation, improve tissue function, and preserve NAD+ levels. Quercetin, spermidine, and fisetin are examples of senolytic agents that have demonstrated efficacy in reducing senescent cell populations and their associated deleterious effects. (6)