NAD+ and Glutathione: Your Cells' Best Defense Against Aging?

Mitochondria are often called the powerhouses of your cells because they produce the energy your body needs to function. But they're also one of the body's largest sources of free radicals, unstable molecules that can damage cells when they build up faster than your body can remove them.

This imbalance, known as oxidative stress, gradually damages mitochondria and other cellular structures. Over time, it’s been linked to many of the changes we associate with aging, including declining energy production and an increased risk of age-related diseases.

Fortunately, your body has a built-in antioxidant network designed to help keep oxidative stress in check. NAD+, glutathione, and ergothioneine are three of its most important players.

NAD+, Glutathione, and Ergothioneine: Better Together

Each has a distinct role, but none works alone.

NAD+ Powers the Network

Your body's antioxidant network can't function without energy. Every time your cells respond to oxidative stress or carry out the thousands of processes needed to stay healthy, they rely on NAD+ to help produce the energy that makes it possible.

As NAD+ levels naturally decline with age, cells become less efficient at producing energy and maintaining healthy mitochondrial function. Researchers believe this decline may accelerate many of the cellular changes associated with aging.

Maintaining healthy NAD+ levels may help your body stay more resilient as you age, supporting a longer healthspan, or the years spent in good health. 

Glutathione Protects the Network

Glutathione is often called the body's “master antioxidant” because it's involved in many of the systems that protect cells from oxidative stress. In addition to neutralizing free radicals, it also helps regenerate other antioxidants after they've been used, keeping your body's entire antioxidant network working efficiently.

Like NAD+, glutathione levels naturally decline with age. As that happens, cells become less equipped to manage oxidative stress and the damage that accumulates over time. This may help explain why lower glutathione levels have also been linked with faster biological aging.

Ergothioneine Strengthens the Network

Ergothioneine is a powerful antioxidant that helps neutralize free radicals before they can damage cells. Unlike most antioxidants, it has a specialized transporter, OCTN1, that helps deliver it to cells exposed to higher levels of oxidative stress. Ergothioneine even accumulates in the mitochondria, where researchers believe it plays an important protective role.

Studies suggest ergothioneine can also help maintain and increase healthy glutathione levels, strengthening your body's overall antioxidant network.

Like NAD+ and glutathione, ergothioneine levels decline with age. Lower levels have been associated with frailty, faster cognitive decline, and several age-related diseases. Increasing evidence suggests higher ergothioneine levels are associated with healthy aging and longevity.

Support the Network that Supports You

The stronger your antioxidant network, the more resilient your cells are to withstand the everyday wear and tear that comes with aging.

Aerobic exercise, fasting, and a low-sugar diet have all been shown to support healthy NAD+ levels. A nutrient-rich diet that includes adequate protein and plenty of colorful fruits and vegetables provides the building blocks your body needs to produce glutathione. And although mushrooms are the richest dietary source of ergothioneine, research suggests that most Americans don't get enough through diet alone, so targeted supplementation may provide additional support.

Aging well isn't about relying on one molecule. It's about strengthening the network that protects you every day.

Devan Ciccarelli is a NASM-Certified Personal Trainer, Nutrition Coach, and Women's Fitness Specialist who writes on health and lives in Florida with her two kids.