Introduction
Sirtuins, revered as the guardians of the genome, are a pivotal group of proteins essential for cellular vitality. This family, comprising seven distinct proteins, relies on the coenzyme NAD+ to execute their functions. Acting as metabolic sensors, sirtuins navigate cellular pathways, modulating gene expression and protein activity in response to internal and external cues.
By harnessing the potent properties of Resveratrol and NMN, VaraSpan® effectively activates sirtuins, the guardians of cell health, by elevating NAD+ levels. But that's not all – fortified with essential nutrients like Vitamin D3, K2, and Omega 3, VaraSpan® goes beyond mere activation, providing comprehensive support for cellular health and inflammation reduction. Experience the synergy of these ingredients as they work harmoniously to enhance sirtuin functionality, promoting robust cellular resilience and vitality in the face of various challenges.
Key Takeaways:
- Understanding Sirtuins, the guardians of our genome: A family of seven proteins, are indispensable for human health orchestrating critical cellular functions.
- The dependency of Sirtuins on NAD+: Sirtuins rely on the coenzyme NAD+ for their function, acting as metabolic sensors that decline with age, impacting sirtuin activity.
- Role of Sirtuins in cellular repairing: Among sirtuins, SIRT1 and SIRT3 stand out, showcasing versatile roles in DNA maintenance, chromatin modification, glucose metabolism, mitochondrial function, and cellular energy production.
Related Products:
- VaraSpan® for cellular aging: Meticulously crafted to activate SIRT1 and possibly other Sirtuins, enhancing NAD+ levels with the NAD+ precursor NMN, Resveratrol and other micronutrients while facilitating direct activation.
Delving Into Sirtuin Functions
![Secret Proteins that Help Control Aging: Sirtuins](https://cdn.shopify.com/s/files/1/0827/3995/3959/files/protein2_480x480.webp?v=1711784600)
Explore the diverse functions of sirtuin members across cellular compartments, from SIRT1's role in DNA maintenance to SIRT3's involvement in mitochondrial metabolism. These proteins collectively regulate crucial cellular processes like metabolism and genome maintenance, forming an interconnected network vital for cellular vitality and homeostasis.
SIRTUINS |
CELLULAR LOCATION |
FUNCTION |
SIRT1 |
Nucleus, cytoplasm |
DNA maintenance, chromatin modification, glucose metabolism, differentiation, neuronal function, mitochondrial function |
SIRT2 |
Cytoplasm, nucleus |
Cell cycle |
SIRT3 |
Mitochondria, nucleus, cytoplasm |
Mitochondrial metabolism, mitochondrial biogenesis and protection, ATP production |
SIRT4 |
Mitochondria |
Mitochondrial metabolism |
SIRT5 |
Mitochondria, cytoplasm, nucleus |
Urea cycle |
SIRT6 |
Nucleus |
DNA maintenance, genome maintenance, telomere maintenance, metabolism |
SIRT7 |
Nucleus |
rDNA transcription |
Takes Two to Tango: NAD+ and Sirtuins in Aging/Longevity Control
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NAD+ and Sirtuins' Interdependence:
NAD+ and sirtuins work hand in hand to regulate aging and longevity. Sirtuins, a protein family with enzymatic functions like deacetylase, rely on NAD+ as a co-substrate. This ancient relationship between NAD+ and sirtuins is pivotal in linking energy regulation to aging control. With age, NAD+ levels decrease, diminishing sirtuin activity and impacting cellular and systemic processes. This decline disrupts communication within cells and between tissues, exacerbating aging effects.
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Evolutionary Significance of Sirtuins
Despite controversies in earlier research, recent studies reaffirm sirtuins' significance as evolutionarily conserved aging regulators. For instance, brain-specific SIRT1 overexpression extends lifespan in mice.
In organisms like yeast, worms, and flies, caloric restriction extends lifespan through mechanisms involving sirtuins and NAD+ pathways. Similarly, in mammals, NAMPT-mediated NAD+ biosynthesis is crucial for sirtuin activity regulation, impacting various metabolic functions.
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NAD+ and Sirtuins' Multifaceted Influence
The functional connection between NAD+ and sirtuins operates at multiple levels, including NAD+ biosynthesis regulation, modulation of sirtuin activity by NAD+ substrates, and competitive utilization of NAD+ among various enzymes.
At a cellular level, compromised communication between the nucleus and mitochondria due to NAD+ decline and reduced sirtuin activity contributes to mitochondrial dysfunction, a hallmark of aging. At a systemic level, disruption in inter-tissue communication between the hypothalamus and adipose tissue due to NAD+ decline affects physiological robustness and contributes to age-associated pathophysiology.
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Strategy for Aging Mitigation
Supplementation of key NAD+ intermediates like NMN & Resveratrol emerge as a potential strategy to mitigate age-associated functional decline and diseases of aging. Understanding the intricate connection between NAD+ and sirtuins sheds light on how energy metabolism influences aging processes and lifespan regulation across different organisms.
Embracing Sirtuins' Promise
![Secret Proteins that Help Control Aging: Sirtuins](https://cdn.shopify.com/s/files/1/0827/3995/3959/files/pexels-james-lee-2017089_1_480x480.jpg?v=1711784701)
In conclusion, the intricate relationship between NAD+ and sirtuins is pivotal in regulating aging and longevity. Sirtuins, crucial for cellular functions, depend on NAD+ availability. As NAD+ levels decline with age, sirtuin activity diminishes, affecting both cellular and systemic processes. However, supplementation like VaraSpan®, containing NMN, resveratrol, and essential micronutrients, shows potential in boosting NAD+ levels and activating sirtuins, possibly mitigating age-related decline. Understanding this interplay sheds light on energy metabolism's role in aging and lifespan regulation, offering innovative approaches for promoting cellular vitality and extending health span.
References
- Dang W. The controversial world of sirtuins. Drug Discov Today Technol 2015;12:e9-e17.
- Araki T, Sasaki Y, Milbrandt J. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 2004;305:1010-1013.
- Shindler K, Ventura E, Rex T, et al. SIRT1 activation confers neuroprotection in experimental optic neuritis. Invest Ophthalmol Vis Sci 2007;48:3602-3609.
- Grabowska W, Sikora E, Bielak-Zmijewska A. Sirtuins, a promising target in slowing down the ageing process. Biogerentology 2017;18(4):447-476.
- Gomes P, Fleming-Outeiro T, Cavadas C. Emerging role of sirtuin 2 in the regulation of mammalian metabolism. Trends Pharmacol Sci 2015;36(11):756-768.
- Nogueiras R, Habegger K, Chaudhary N, et al. Sirtuin 1 and sirtuin 3: physiological modulators of metabolism. Physiol Rev 2012;92:1479-1514.
- Min Z, Gao J, Yu Y. The roles of mitochondrial SIRT4 in cellular metabolism. Front Endocrinol 2019;9:783.
- Li Y, Li S, Lin C. Effect of resveratrol and pterostilbene on aging and longevity. Biofactors 2018;44(1):69-82.
- Polletta L, Vernucci E, Carnevale I, et al. SIRT5 regulation of ammonia-induced autophagy and mitophagy. Autophagy 2015;11(2):253-270.
- Huang P, Riordan S, Heruth D, et al. A critical role of nicotinamide phosphoribosyltransferase in human telomerase reverse transcriptase induction by resveratrol in aortic smooth muscle cells. Oncotarget 2015;6(13):10812-10824.
- Lu S, Kato M, Lin S. Assimilation of endogenous nicotinamide riboside is essential for calorie restriction-mediated life span extension in Saccharomyces cerevisiae. J Biol Chem 2009;284:17110-17119.
- Sun Q, Jia N, Wang W. Activation of SIRT1 by curcumin blocks the neurotoxicity of amyloid-β25-35 in rat cortical neurons. Biochem Biophys Res Commun 2014;448(1):89-94.
- Grabowska W, Suszek M, Wnuk M, et al. Curcumin elevates sirtuin level but does not postpone in vitro senescence of human cells building the vasculature. Oncotarget 2016;7(15):19201-19213.
- Kireev R, Vara E, Tresquerres J. Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats. Biogerontology 2013;14(4):431-442.