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SIRT3, NAD+, and Healthy Aging: What Your Genetics May Mean

Nicotinamide adenine dinucleotide, or NAD+, is a central molecule for cellular energy, DNA repair, and defense against stress. It supports a family of proteins called sirtuins that help regulate cellular health and aging. SIRT3 is a sirtuin that works inside mitochondria, the cell structures responsible for producing energy. SIRT3 depends on NAD+ to activate pathways that improve mitochondrial function, reduce oxidative damage, and support metabolic flexibility.

NAD+ levels decline with age, which can reduce SIRT3 activity and compromise mitochondrial resilience. Lifestyle choices and targeted nutrients can help maintain NAD+ and support SIRT3 function. Below you will find a clear explanation of possible genetic results for the SIRT3 variant rs511744, practical lifestyle and nutrition ideas to support NAD+ and mitochondrial health, and guidance on how to discuss findings with your healthcare provider.

Why SIRT3 and NAD+ Matter

  • Energy production: SIRT3 helps mitochondria run efficiently, which supports stamina, metabolic health, and cellular repair.
  • Antioxidant protection: SIRT3 activates enzymes that lower oxidative stress and protect against cellular damage.
  • Longevity pathways: SIRT3 is linked to biological processes that promote healthy aging when supported by adequate NAD+.

Practical Ways to Support NAD+ and SIRT3

Whether or not your genetics suggest enhanced SIRT3 activity, you can use diet, supplements, and lifestyle strategies to maintain NAD+ and promote mitochondrial health.

Diet and Nutrition

  • Eat foods rich in NAD+ precursors: poultry, fish, eggs, dairy, lean meats, and whole grains provide niacin and tryptophan.
  • Include tryptophan-containing plant foods: nuts, seeds, soy products, and legumes.
  • Support methylation and one-carbon metabolism: eat leafy greens, cruciferous vegetables, legumes, and foods high in folate and B vitamins.
  • Maintain balanced protein intake: amino acids are building blocks for NAD+ precursors and mitochondrial enzymes.

Supplements to Consider

  • Nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN): commonly used to support NAD+ levels. Discuss benefits and risks with your provider.
  • B complex vitamins: support NAD+ synthesis and energy metabolism.
  • Antioxidant support when appropriate: nutrients like vitamin C, vitamin E, and polyphenol-rich foods may complement mitochondrial protection.

Exercise and Movement

  • Regular aerobic exercise increases mitochondrial biogenesis and supports NAD+ turnover.
  • Incorporate resistance training to maintain muscle mass and metabolic health.
  • Short high intensity intervals can stimulate mitochondrial adaptations, but tailor intensity to fitness level and medical status.

Fasting, Meal Timing, and Metabolic Stress

  • Intermittent fasting or controlled calorie reduction may boost NAD+ and sirtuin activity in some individuals.
  • Prioritize consistent meal timing and avoid prolonged overeating that could blunt metabolic benefits.

Sleep, Stress, and Environmental Factors

  • Quality sleep supports metabolic recovery and mitochondrial maintenance.
  • Chronic stress can impair NAD+ metabolism; use stress reduction techniques such as mindfulness, moderate exercise, and social support.
  • Cold exposure such as brief cold showers or cold-water immersion may enhance mitochondrial function for some people. Start gradually and only if medically appropriate.

How to Use This Information

Your genes are one factor among many that influence health. Genetic variants can change how your body responds to environmental factors. Lifestyle choices often have powerful effects that can complement or offset genetic predispositions. If you consider supplements or major diet or exercise changes, consult your healthcare provider, especially if you are pregnant, nursing, taking medications, or have chronic health conditions.

Two effect alleles (TT) — Increased lifespan association

You have the TT genotype for rs511744 in SIRT3, carrying two copies of the effect allele. Research links this variant with increased lifespan in some studies. In practical terms, this genotype may support stronger SIRT3 activity when NAD+ is available. Enhanced SIRT3 activity helps mitochondria produce energy more efficiently and activates cellular antioxidant defenses that reduce oxidative damage.

What you can do to support this advantage

  • Focus on NAD+ precursors in your diet: include poultry, fish, eggs, dairy, and whole grains.
  • Consider NMN or NR supplements after discussing with your provider to help maintain NAD+ as you age.
  • Maintain regular aerobic and resistance exercise to promote mitochondrial biogenesis.
  • Prioritize high quality sleep and consider intermittent fasting or time-restricted eating if appropriate.
  • Use stress management and gradual cold exposure protocols only if safe for you.
One effect allele (CT) — Possible increased lifespan

You have the CT genotype for rs511744, carrying one copy of the effect allele. This variant may be associated with a modest increase in SIRT3 activity in some contexts. Your SIRT3 function may respond well when NAD+ levels are sufficient.

Actions to optimize benefit

  • Eat foods rich in niacin and tryptophan such as poultry, fish, and legumes.
  • Discuss NR or NMN supplements with your healthcare provider to support NAD+ levels as needed.
  • Engage in consistent exercise that includes both aerobic and strength components.
  • Consider intermittent fasting or reduced calorie periods under medical guidance to stimulate SIRT3 and NAD+ pathways.
  • Prioritize sleep and recovery as part of an overall mitochondrial health plan.
No effect alleles (CC) — Typical SIRT3 activity

You have the CC genotype for rs511744, which is associated with typical SIRT3 activity. This does not mean you cannot support healthy aging. Lifestyle and nutritional strategies can help maintain NAD+ and optimize SIRT3 function regardless of genetic baseline.

Steps to support SIRT3 and mitochondrial health

  • Consume a balanced diet with niacin and tryptophan sources: lean protein, whole grains, and plant proteins.
  • Consider discussing NR or NMN supplements with your provider if you are interested in supporting NAD+ levels.
  • Adopt a regular exercise routine with both aerobic and resistance components.
  • Use time-restricted eating or other metabolic interventions cautiously and with clinical guidance.
  • Focus on sleep, stress management, and regular medical checkups to support overall metabolic resilience.

Next Steps and Consultations

Genetic information can guide targeted lifestyle changes, but it is not a diagnosis. Consider discussing your results with a clinician, genetic counselor, or other qualified healthcare professional to tailor recommendations to your medical history, medications, and health goals. If you pursue supplements like nicotinamide riboside or NMN, review safety, dosing, and interactions with your provider.

Important disclaimer: PlexusDx does not provide medical advice. This information is educational and is not a substitute for professional medical guidance. Always consult your healthcare provider before making changes to medications, supplements, diet, or exercise routines.