What are the mechanisms behind the anti-aging effects of sirtuins and NAD+ precursors?

Introduction

Sirtuins and NAD+ precursors have garnered significant attention for their potential anti-aging effects. Sirtuins are a family of NAD+-dependent deacetylases that play crucial roles in cellular metabolism, stress resistance, and longevity. NAD+ (nicotinamide adenine dinucleotide) is a vital coenzyme that influences various cellular processes, including those regulated by sirtuins. Understanding the mechanisms behind the anti-aging effects of sirtuins and NAD+ precursors can provide insights into therapeutic strategies for age-related diseases.

Key Insights

Sirtuin Activation and Caloric Restriction:
- Sirtuins, particularly SIRT1 and SIRT3, are activated by caloric restriction, fasting, and exercise, which are known to extend lifespan and confer neuroprotective effects .
NAD+ Levels and Sirtuin Activity:
- NAD+ levels decline with age, leading to reduced sirtuin activity. Supplementing with NAD+ precursors can restore NAD+ levels, thereby enhancing sirtuin function and mitigating age-related cellular dysfunction .
Mitochondrial Function and SIRT3:
- SIRT3, a mitochondrial sirtuin, enhances mitochondrial function by deacetylating and activating enzymes involved in energy metabolism and antioxidant defenses. This action helps prevent mitochondrial deficits associated with aging and neurodegeneration.
DNA Repair and Cellular Metabolism:
- Sirtuins, through their NAD+-dependent deacetylase activity, play a role in DNA repair, cellular metabolism, and mitochondrial biogenesis. These processes are crucial for maintaining cellular health and longevity .
Neuroprotection and Alzheimer's Disease:
- SIRT1 has been shown to reduce amyloidogenic processing of amyloid-β protein precursor (APP) by increasing α-secretase activity, which may have therapeutic potential for Alzheimer's disease.

Conclusion

The anti-aging effects of sirtuins and NAD+ precursors are primarily mediated through their roles in enhancing cellular metabolism, mitochondrial function, DNA repair, and neuroprotection. Sirtuins are activated by increased NAD+ levels, which can be achieved through caloric restriction, exercise, and supplementation with NAD+ precursors. These mechanisms collectively contribute to improved cellular health and longevity, offering promising avenues for therapeutic interventions in age-related diseases.

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What are the mechanisms behind the anti-aging effects of sirtuins and NAD+ precursors?

Summary

Introduction

Key Insights

Conclusion

Sources and full results

The sirtuin pathway in ageing and Alzheimer disease: mechanistic and therapeutic considerations

The sirtuin pathway may play a role in Alzheimer's disease onset and development, and therapeutic upregulation of SIRT1 may potentially improve neuropathology through inhibition of amyloidogenesis.

Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration

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NAD+: a crucial regulator of sirtuin activity in aging

NAD+ supplementation may promote healthy aging by regulating sirtuin function and attenuating age-related functional defects.

Regulatory Effects of NAD+ Metabolic Pathways on Sirtuin Activity.

NAD+ metabolic pathways regulate sirtuin activities, impacting cell physiology and potentially offering novel therapeutic options for aging diseases.

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Sirtuin proteins play a crucial role in regulating premature cellular senescence and accelerated aging, potentially impacting anti-aging mechanisms.

Sirtuins in aging and disease.

Sirtuin genes may extend life span by boosting mitochondrial biogenesis, which may reduce reactive oxygen species production and potentially lead to novel drugs to combat aging diseases.

Sirtuins, aging and diseases

Sirtuins play a crucial role in aging and diseases by regulating metabolism, protein acetylation, and calorie restriction, which extends life span and protects against many aging diseases.

Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1-Dependent Manner.

Nicotinamide mononucleotide (NMN) effectively restores renal SIRT1 activity and NAD+ content in aged mice, potentially offering a precise treatment for acute kidney injury in aged patients.

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