Longevity compounds that don’t make the headlines

NAD+, spermidine, and glutathione aren’t household names, but they’re central to how your body repairs itself, manages energy, and slows biological aging. 

Their levels decline steadily with age, long before symptoms show up. 

That decline affects everything from metabolism to memory. Researchers are now finding ways to restore them through fasting, movement, and targeted compounds. 

While some of the results are early, others are already changing how we think about aging.

This molecule declines with age

NAD+ (nicotinamide adenine dinucleotide) is essential for mitochondrial energy production and activating sirtuins, which are longevity-related proteins that regulate cellular repair and inflammation.

NAD+ levels can decline by over 50% by your 40s, reducing your body’s ability to recover and stay metabolically efficient. 

Low NAD+ has been linked to fatigue, neurodegeneration, and metabolic disorders.

You can naturally increase NAD+ through hormetic stressors like fasting, exercise, and heat exposure. Supplements like NMN and NR are designed to boost NAD+ with early human studies showing improvements in insulin sensitivity and muscle function, but research is still catching up to the hype.

Cellular repair and defense

Spermindine

Spermidine supports autophagy, the body’s cleanup system for damaged cells. As we age, this process slows, which can lead to cellular dysfunction and inflammation. Spermidine helps restart it. 

Found naturally in natto, aged cheese, mushrooms, and wheat germ, it’s also available in supplement form. A 2021 human trial showed memory improvements in older adults who supplemented daily. 

It also pairs well with fasting, amplifying autophagy through different pathways. Aim for around 1mg per day when supplementing, using wheat germ-derived sources.

Glutathione

Otherwise known as the master antioxidant, glutathione is critical for detox, immune function, and protecting cells from oxidative stress. 

Glutathione levels will decline with age, especially under chronic inflammation or poor sleep, but you can support it naturally with garlic, onions, cruciferous vegetables, and quality sleep. 

If supplementing, NAC (600–1200mg/day) is a well-researched precursor. Liposomal glutathione is another option, particularly if your detox load is high. Think of it as foundational maintenance, especially if you’re stacking other longevity interventions.

Two streams of assistance

While some longevity supplements are promising, many haven’t been fully validated in human trials. If you’re considering NAD+ boosters, spermidine capsules, or AKG powders, start with trusted brands and look for third-party testing.

That said, the most effective way to boost these compounds comes through natural means:

• exercise

• intermittent fasting

• polyphenol-rich diets

• sleep

• heat/cold exposure. 

All of these protocols have documented effects on NAD+, glutathione, and autophagy. 

As always, consult your healthcare professional before deciding on what supplement works best for you.

Further molecular research

Early NAD+ studies show benefits, including improved muscle strength, better metabolic markers, and increased mitochondrial activity in older adults taking NMN or NR. However, results vary based on dosage and form.

A study on both human cells and mice found spermidine helped grow new blood vessels in areas with poor blood flow, speeding up recovery

NAC supplementation for glutathione has been shown to improve immune function in the elderly and reduce oxidative stress markers.

Although the research is still in its early days for some of these molecules, they all show signs of promise as an additional way to maintain balance within the body.  

As we learn more, longevity is becoming more and more about molecule management. The future of aging may come down to how well we maintain what we typically never measured in the past.

TLDR TRIO

📈 NAD+, spermidine, and glutathione support energy, repair, and detox

✅ All decline with age but can be restored naturally or with targeted support

⌛ Prioritize fasting, movement, and sleep before adding supplements like NMN, NAC, or spermidine