NAD+ and Rapamycin: The Longevity Stack I’ve Been Running For 2 Years (Full Protocol and Bloodwork)

Two Compounds That Changed How I Think About Aging

I’ve experimented with a lot of compounds over the years. Most of them are performance-focused — build more muscle, recover faster, optimize hormones. But about two years ago, I started paying serious attention to the longevity research, and two compounds kept showing up in the data with consistency that I couldn’t ignore: NAD+ precursors and low-dose rapamycin.

This isn’t about living to 150 or some sci-fi nonsense. This is about maintaining high-level physical and cognitive function as I age. I’m not interested in just adding years to my life — I want those years to be spent training hard, building businesses, creating content, and living the way I want to live. That requires my biology to keep up with my ambition.

NAD+: What It Is and Why It Declines

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme present in every cell of your body. It’s essential for energy metabolism, DNA repair, cellular signaling, and the function of sirtuins — a family of proteins that regulate aging at the cellular level.

The problem is that NAD+ levels decline significantly with age. By the time you hit 50, your NAD+ levels can be 50% or lower compared to your 20s. This decline is associated with virtually every hallmark of aging: mitochondrial dysfunction, increased inflammation, impaired DNA repair, metabolic slowdown, and cognitive decline.

The research on NAD+ restoration through precursor supplementation (NMN and NR) has exploded in the last five years. David Sinclair’s work at Harvard brought it into the mainstream, but the underlying science has been building for decades.

My NAD+ Protocol

I use nicotinamide mononucleotide (NMN) as my primary NAD+ precursor. Here’s my current protocol:

NMN: 500mg per day, taken in the morning on an empty stomach.

I’ve tried doses ranging from 250mg to 1000mg. For me, 500mg is the sweet spot where I notice clear benefits without diminishing returns. I take it first thing in the morning because NAD+ plays a role in circadian rhythm regulation, and morning dosing seems to align better with natural energy patterns.

I take it sublingual when possible — held under the tongue for 60-90 seconds before swallowing. Sublingual absorption bypasses first-pass liver metabolism and appears to increase bioavailability based on the limited pharmacokinetic data available.

Trimethylglycine (TMG): 500mg per day, taken with NMN.

This is an important addition that most NMN protocols skip. NMN metabolism consumes methyl groups. If you’re taking NMN long-term without a methyl donor like TMG, you can deplete your methyl pool, which impacts everything from homocysteine levels to DNA methylation. TMG is cheap insurance against that.

What I’ve Noticed From NAD+ Restoration

The most consistent benefit has been energy. Not stimulant-like energy — more like a baseline elevation in my capacity for sustained work, both physical and mental. My workouts haven’t changed in structure, but my ability to maintain intensity through a 90-minute session has noticeably improved.

Sleep quality improved within the first month. I track sleep with an Oura ring, and my deep sleep percentage increased from roughly 15-17% to 20-23% consistently after starting NMN. Deep sleep is when the majority of physical recovery happens, so this has downstream effects on everything.

The cognitive effects are subtler but real. I process information faster, I’m sharper in conversations, and the afternoon fog that used to hit me around 2-3pm has largely disappeared. I can’t isolate NMN as the sole cause since I run multiple compounds, but the correlation with starting NMN was clear.

Rapamycin: The Drug That Scares Most People

If NMN is the feel-good longevity compound, rapamycin is the one that requires some courage. Originally developed as an immunosuppressant for organ transplant patients (at high daily doses), rapamycin has emerged as perhaps the most robust pharmacological intervention for extending lifespan in animal studies.

The data is remarkable: rapamycin has extended lifespan in every organism it’s been tested in — yeast, worms, flies, and mice. In mice specifically, it increased maximum lifespan by 9-14% even when started late in life. No other drug has that track record across species.

The mechanism is mTOR inhibition. mTOR (mechanistic target of rapamycin) is a nutrient-sensing pathway that, when chronically activated, promotes growth at the expense of maintenance and repair. By intermittently inhibiting mTOR, rapamycin essentially shifts your biology from growth mode into repair and maintenance mode — which is exactly what you want as you age. This is a direct application of the Tony Huge Laws of Biochemistry Physics — you’re manipulating a master regulatory pathway to force a systemic shift in cellular priorities.

My Rapamycin Protocol

Rapamycin (Sirolimus): 5mg once per week.

This is the critical distinction from transplant use. Transplant patients take rapamycin daily at doses of 2-5mg to maintain continuous immunosuppression. The longevity protocol uses intermittent dosing — once weekly — which has a fundamentally different effect on the immune system.

Weekly low-dose rapamycin has been shown to actually enhance certain aspects of immune function (particularly the response to vaccines in elderly patients, as shown in the Joan Mannick/resTORbio studies) while still providing the cellular maintenance benefits of intermittent mTOR inhibition.

I take my weekly dose on Friday evenings. mTOR inhibition can temporarily reduce protein synthesis efficiency, so I time it away from my heaviest training days (Monday-Wednesday). By Monday, mTOR signaling has fully recovered, and I train with full anabolic capacity.

Cycling: I do 8 weeks on, 4 weeks off. This cycling approach is based on the available literature suggesting that intermittent exposure is sufficient for the longevity benefits while minimizing any potential for cumulative immunosuppression.

The Bloodwork Evidence

I’ve been tracking comprehensive bloodwork quarterly since starting this protocol. Here’s what the data shows:

Fasting glucose: Dropped from 92-96 mg/dL range to consistently 82-87 mg/dL. Rapamycin can temporarily raise blood glucose (it’s one of the known side effects at higher doses), but at my weekly 5mg dose, the opposite has occurred. Improved glucose regulation is one of the hallmarks of mTOR optimization.

Inflammatory markers: hs-CRP has been consistently below 0.5 mg/L since month 3 of the protocol. Previously it hovered around 1.0-1.5 mg/L. Lower systemic inflammation is one of the most well-supported effects of rapamycin in the literature.

Lipid panel: Total cholesterol essentially unchanged. Triglycerides dropped modestly. HDL increased slightly. The lipid impact of weekly rapamycin at this dose appears to be neutral to mildly positive, which is consistent with the published data on low-dose intermittent protocols.

CBC: White blood cell count, lymphocytes, and neutrophils all within normal range throughout. This is the immunosuppression concern that most people have, and at weekly 5mg dosing, it simply hasn’t materialized in my bloodwork.

Kidney and liver function: All markers (creatinine, BUN, ALT, AST, GGT) consistently normal. No signal of organ stress.

The Synergy Between NAD+ and Rapamycin

These two compounds work through complementary mechanisms that make them particularly effective together.

NAD+ restoration supports mitochondrial function, DNA repair, and sirtuin activation — essentially giving your cells more resources to maintain themselves. Rapamycin, through mTOR inhibition, activates autophagy — the process by which cells clean up damaged proteins and organelles.

Together, you’re simultaneously improving cellular repair capacity (NAD+) and activating the cellular cleanup program (rapamycin). It’s like giving the maintenance crew better tools AND scheduling regular deep-cleaning sessions. One without the other is good. Both together is substantially better.

Interesting Perspectives

Beyond the core longevity benefits, this stack opens up some unconventional angles. The cognitive and sleep improvements from NAD+ precursors suggest potential applications for shift workers or individuals with circadian rhythm disorders, acting as a metabolic reset. The anti-inflammatory effects of rapamycin, distinct from traditional NSAIDs, present a unique angle for managing age-related low-grade inflammation (inflammaging) that underlies many chronic conditions.

From a performance standpoint, the enhanced recovery and mitochondrial efficiency could be leveraged by endurance athletes. The principle of intermittent mTOR inhibition to prioritize repair could be cross-applied to training periodization—structuring de-load weeks to mimic the biological “clean-up” phase induced pharmacologically by rapamycin. This stack represents a move from reactive health management to proactive system optimization, a core tenet of advanced biohacking.

Who Should Consider This

This protocol is most appropriate for men and women over 35 who are serious about long-term health optimization and comfortable with a data-driven, bloodwork-monitored approach.

Rapamycin specifically requires a prescription in the US and most countries. It should be used under medical supervision with regular bloodwork monitoring. This isn’t something you order from a research chemical site and wing it — the pharmacology is serious and deserves serious oversight.

NMN is available over the counter and has an excellent safety profile. It’s a reasonable addition to almost any supplement regimen for anyone over 30.

If you’re already optimizing your hormones, using peptides for recovery and performance, and dialing in your nutrition and training — the longevity stack is the next logical layer. Because what’s the point of building a great physique and a great life if your biology gives out at 65?

I plan to be training, creating content, and running businesses well into my 70s and beyond. This protocol is part of how I intend to make that happen.

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