Nicotinamide Adenine
Dinucleotide

1906-1930

The Coenzyme Discovery

Finding Life's Essential Cofactor

In 1906, Arthur Harden and William Young were studying how yeast converts sugar into alcohol. They found that fermentation required not just enzymes but also a heat-stable factor they couldn't identify.

Harden called this mystery substance a 'cozymase' — what we now know as NAD+. He won the 1929 Nobel Prize for this discovery. Other Nobel Prizes followed as scientists characterized NAD+'s structure and function.

By the mid-20th century, biochemists understood that NAD+ was essential for metabolism. It carried electrons in hundreds of reactions, converting food into cellular energy. Without NAD+, life couldn't exist.

1990s-2000s

The Sirtuin Connection

Linking NAD+ to Aging

In the 1990s, scientists discovered sirtuins — a family of proteins that seemed to protect cells against aging. Organisms with more active sirtuins lived longer. Organisms with less active sirtuins aged faster.

Then came a crucial discovery: sirtuins needed NAD+ to work. They were NAD+-dependent enzymes. When NAD+ levels were high, sirtuins were active and cells stayed healthy. When NAD+ levels dropped, sirtuins couldn't do their job.

Suddenly, NAD+ wasn't just a metabolic coenzyme. It was a potential key to controlling aging itself.

2005-2015

The Decline Problem

NAD+ Falls with Age

Researchers made a troubling observation: NAD+ levels decline dramatically with age. By middle age, humans have perhaps half the NAD+ they had in youth. By old age, levels may drop to a fraction.

This decline correlated with many aspects of aging: reduced energy, impaired DNA repair, accumulation of cellular damage. The sirtuins that protected against aging were running low on the fuel they needed.

David Sinclair at Harvard became NAD+'s most prominent champion. His lab showed that boosting NAD+ in aged mice improved their health markers. Old mice given NAD+ precursors had more energy, better metabolism, and healthier tissues.

2015-2020

The Supplement Era

NMN and NR Go Mainstream

You can't take NAD+ directly — it doesn't survive digestion. But you can take precursors that your body converts to NAD+. Two emerged as leaders: NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside).

Companies began selling these supplements, marketing them as anti-aging compounds. David Sinclair revealed he took NMN himself. Investors poured money into longevity startups. NAD+ became the hottest molecule in anti-aging science.

Skepticism remained. Mouse studies were promising, but mice aren't humans. Clinical trials were just beginning. The supplements were expensive, and evidence for dramatic anti-aging effects in humans was limited.

2020-Present

The Evidence Builds

From Hype to Science

Human clinical trials are finally providing data. Some show that NMN and NR do raise NAD+ levels in people. Some show modest improvements in metabolic markers, muscle function, and cellular health.

But the dramatic anti-aging effects seen in mice haven't clearly translated to humans yet. NAD+ boosting may help, but it's not a fountain of youth. The complexity of human aging resists simple solutions.

Research continues. Scientists are exploring why NAD+ declines (beyond just age) and whether preventing that decline works better than trying to restore it. The molecule discovered in 1906 remains at the center of 21st-century aging science.