From myth to mitochondria -my top ten longevity strategies
- Dr. S. Rallis DC, ND
- May 12
- 6 min read
Five hundred years have passed since Spanish explorer Juan Ponce de León, discovered the mythological "fountain of youth" in what is now, present day, St. Augustine, Florida. [As an aside, if you ever get the chance to visit St. Augustine, located just 30 minutes south of Jacksonville, Florida, and 30 minutes north of Daytona, I highly recommend it!]
While the Fountain of Youth story may be more legend than fact, it reflects a timeless human tradition: looking for any way to extend not just lifespan, but healthspan — the number of years we stay strong, sharp, and independent. Look no further than the myriad of biohackers on social media.
In the spirit of my recent visit, I'd like to share my top ten strategies for improving health and lifespan, and I'll also share what I believe are the two most promising IV therapies for longevity.
My Top 10 SCIENCE-BACKED Longevity Strategies
1. Caloric Restriction (Without Malnutrition)
Reducing total calorie intake by 10–25%, without nutrient deficiency, has been shown to slow metabolic rate, lower inflammation, and enhance autophagy — cellular "cleanup" — all of which may delay aging and disease onset.
Evidence: Consistent across species (worms, flies, mice, primates). In humans (CALORIE trial), caloric restriction without malnutrition improved markers associated with aging (lowered inflammation, improved insulin sensitivity, slowed metabolic rate).
Mechanism: Reduces mTOR signaling, oxidative stress, and inflammation; improves autophagy.
2. Optimal Physical Activity (Especially Strength + Zone 2 Aerobic Training)
Regular movement, particularly aerobic exercise at a moderate intensity ("Zone 2") and resistance training, supports cardiovascular health, preserves muscle mass, improves insulin sensitivity, and reduces all-cause mortality.
Evidence: Exercise is perhaps the single most powerful non-pharmacological intervention for lifespan and healthspan.
Best type:
Zone 2 aerobic exercise (60–70% max heart rate) improves mitochondrial efficiency.
Strength training prevents sarcopenia, fractures, and frailty.
Meta-analyses show 20–40% reduced mortality risk in physically active people.
3. Protein Intake and Muscle Mass Preservation
Maintaining lean muscle through adequate protein and strength training is one of the strongest predictors of independence and resilience in aging adults, helping prevent frailty, falls, and metabolic decline.
Evidence: Higher muscle mass and strength correlate more closely with longevity than even blood pressure or cholesterol in older adults.
Mechanism: Prevents frailty, maintains insulin sensitivity, reduces inflammatory burden.
4. Avoidance of Tobacco and Minimized Alcohol Use
Eliminating smoking and minimizing alcohol dramatically lowers the risk of cancer, heart disease, and neurodegeneration — and these are among the most modifiable risk factors for premature death.
Evidence: Smoking cessation at any age improves lifespan. Alcohol in moderate-to-heavy use increases all-cause mortality.
Modern shift: Even "moderate" drinking is now associated with subtle brain shrinkage and increased cancer risk.
5. Metabolic Health Maintenance (Especially Insulin Sensitivity)
Keeping blood sugar, insulin, triglycerides, and waist circumference in optimal ranges helps prevent the chronic diseases most associated with aging, including diabetes, cardiovascular disease, and Alzheimer’s.
Evidence: Chronically elevated fasting insulin, glucose, triglycerides, and visceral fat are strongly predictive of early mortality.
Mechanism: Prevents cardiovascular disease, cancer, and neurodegeneration.
Key tactics: Maintain a low fasting insulin, avoid central obesity, periodic metabolic resets (fasting, carb cycling).
6. Adequate and Optimized Sleep (7–9 Hours, Good Quality)
Sleep is essential for cognitive function, hormonal balance, and cellular repair. Poor sleep accelerates biological aging and increases the risk of nearly every age-related disease.
Evidence: Poor sleep (short or fragmented) is associated with increased risk of heart disease, diabetes, Alzheimer’s, and cancer.
Mechanism: Sleep maintains glymphatic clearance (brain detox), hormone regulation, immune function.
Best practices: Consistent schedule, cool dark room, no screens before bed, mindfulness for sleep onset.
7. Targeted Nutritional Optimization (Modified Mediterranean/Personalized nutrition) that optimize antioxidant status, insulin status and reduce inflammation
A diet rich in colorful vegetables, omega-3 fats, fiber, and phytonutrients — like a Mediterranean or personalized anti-inflammatory plan — fuels the body without promoting chronic inflammation or insulin resistance.
Evidence: Diets rich in vegetables, healthy fats (olive oil, omega-3s), fiber, moderate protein, and low glycemic load are associated with lower all-cause mortality.
Key nutrients: Omega-3 fatty acids, polyphenols (berries, dark chocolate, green tea), magnesium, potassium, zinc.
8. Regular Health Screening and Early Risk Detection
Routine screenings (e.g., blood work, imaging, cancer screenings) enable early intervention before diseases become life-threatening, increasing both lifespan and quality of life.
Evidence: Screenings like colonoscopy, mammography (individualized), coronary calcium scoring, metabolic panels can detect disease early when it's most treatable.
Philosophy: Don’t wait for symptoms — early detection = longer life.
9. Social Connection and Psychological Resilience
Strong relationships and psychological resilience lower stress hormones and inflammation, improve immune function, and are strongly correlated with longer lifespan and better aging outcomes.
Evidence: Strong relationships and psychological well-being (low loneliness, low chronic stress) are equally predictive of longevity as biological risk factors.
Mechanism: Reduces stress hormones (like cortisol), inflammation, and supports healthier behaviors.
10. Periodic Hormetic Stressors (e.g., Fasting, Heat, Cold, Hypoxia Training)
Intermittent exposure to controlled stressors like cold plunges, sauna therapy, intermittent fasting, or altitude training can activate pathways linked to cellular renewal, DNA repair, and mitochondrial biogenesis.
Evidence:
Intermittent fasting improves metabolic flexibility and autophagy.
Sauna use reduces cardiovascular and Alzheimer's risk (shown in Finnish longitudinal studies).
Cold exposure improves mitochondrial function, possibly brown fat activity.
Philosophy: “What doesn't kill you makes you stronger” — in small, repeated doses.
IV Therapy for Longevity: The top 2 IV therapies for longevity
While lifestyle foundations like nutrition, exercise, and sleep form the backbone of any longevity strategy, targeted intravenous (IV) therapies offer a powerful way to support cellular health more directly. By bypassing the digestive system and delivering nutrients straight into the bloodstream, IV therapy can rapidly restore critical compounds that decline with age — especially those involved in energy production, detoxification, and oxidative stress defense. Two of the most promising IV therapies in this space are glutathione and NAD+. These compounds don’t just help you feel better in the short term — they’re increasingly being studied for their potential to slow the aging process itself.
1. Glutathione IV
Why it matters for longevity:
Glutathione is the body's master antioxidant.
It neutralizes reactive oxygen species (ROS) and peroxides, which cause cellular damage and accelerate aging (oxidative stress is a core part of the "hallmarks of aging" model).
Glutathione declines naturally with age.
IV advantage: Oral glutathione is poorly absorbed. IV administration gives an immediate and high plasma level.
Evidence:
Lower glutathione levels are consistently associated with shorter lifespan across species.
Clinical studies show glutathione supplementation improves insulin resistance, immune function, and mitochondrial function.
There's also emerging evidence it may help detoxify cellular debris in aging cells.
Bottom Line: IV glutathione is arguably the most important foundational defense against age-related oxidative damage.
2. NAD+ IV
Why it matters for longevity:
NAD+ (Nicotinamide Adenine Dinucleotide) is essential for energy production, DNA repair, sirtuin activation, and cellular resilience.
NAD+ levels plummet with age — by age 50 you may have half the NAD+ you had at 20.
IV advantage: Oral NAD+ supplements (like NMN or NR) have limited and variable bioavailability. IV provides direct bloodstream delivery, bypassing first-pass metabolism.
Evidence:
Boosting NAD+ has been shown to enhance mitochondrial health, DNA repair, and resilience to metabolic stress in multiple animal and early human studies.
NAD+ supplementation increases lifespan in model organisms (worms, mice).
In humans, it shows promise for improving cognitive function, energy, and metabolic health, although long-term survival data is still emerging.
Bottom Line: IV NAD+ is a potent tool to recharge cellular energy and restore youthful resilience at the mitochondrial level.
Important Nuances
Frequency matters.Both glutathione and NAD+ IVs aren't "one-and-done." To have true longevity effects, you'd want periodic, strategic administration — for example:
Glutathione: 1–2 times weekly in high oxidative stress states (illness, post-chemo, toxin exposure), or monthly for baseline support.
NAD+: 1–2 high-dose infusions monthly, or a short course of daily infusions over 4–5 days 2–3 times per year (like a cellular "reset").
Dose matters.For NAD+, slow infusion rates (over 2–4 hours) are critical — fast NAD+ infusions cause nausea, chest tightness, and discomfort.
Synergy matters. In a real "longevity protocol," you would combine glutathione and NAD+ with:
Correcting key nutrient deficiencies (zinc, magnesium, selenium).
Mitochondrial co-factors (like CoQ10, lipoic acid).
Managing insulin/glucose.
Physical activity to force mitochondrial biogenesis.
While the Fountain of Youth may have been a myth, the modern science of longevity is anything but. Today, we understand that aging isn’t just a number — it’s a cellular process shaped by oxidative stress, mitochondrial decline, inflammation, and nutrient depletion. IV therapies like glutathione and NAD+ allow us to target those processes directly, offering a proactive, personalized approach to aging well. When combined with foundational lifestyle strategies — from movement and sleep to nutrition and stress resilience — they become part of a comprehensive plan to not just add years to your life, but life to your years. Longevity isn’t about chasing youth — it’s about investing in your future health, one cell at a time.