The History Behind the Science of Aging

Ever since the first human saw their reflection in water, we've sought to reverse—or at least hide—the effects of aging. Our efforts over the centuries to thwart aging have led us to some rather scary methods. The ancient Egyptians basically invented cosmetics, developing hair growth serums for men and night creams for women. Some even turned to leeches and crocodile dung as elaborate topical treatments designed to make them appear healthier and younger. Regularly self-poisoning with ammonia, arsenic, mercury, and lead were all part of many Victorian women’s daily routine. In the 15th century, a Hungarian noblewoman named Countess Elizabeth Báthory de Ecsed went so far as to bathe in human blood in a vain attempt to restore her youth.

While focusing on outward appearances may seem to be the easier way to combat aging, those attempts almost never address the root cause of what’s going on underneath our skin. Let's investigate the history behind the science of aging to better understand the aging process.

Chapter 1: Understanding aging as a biological process.

Age may be nothing but a number, but aging is a biological process. Also called “senescence,” aging is the gradual deterioration of our most basic functions. You don’t need to be a biogerontologist (a scientist who studies biological aging) to know that that deterioration goes much deeper than the skin.

The symptoms we associate with aging, like wrinkles, loose skin, and stiff joints, are all just outward signs of what is happening inside our bodies at a microscopic level. Our cells are, in fact, failing. Today, researchers are beginning to study just how much of that failure is due to the decay of strangely shaped organelles known as the mitochondria. 

Chapter 2: Exploring the work behind the mitochondria.

As the “powerhouses” of the cell, the mitochondria generate 90% of the energy our cells need to survive. They function like miniature, self-contained organs living and dying all while inside of our cells. But like any organism, the mitochondria rely on a power source to keep them charged. That source is an essential molecule known as NAD+ (nicotinamide adenine dinucleotide).

The story of NAD+’s discovery begins with beer. In the mid-19th century, Louis Pasteur collaborated with French brewers to study the microscopic forces at work during the brewing process. He identified “diseases” of beer—microbes that could cause the beer to spoil—as well as the important role that yeast played in the process of alcoholic fermentation.

In 1906, Arthur Harden and William John Young expanded Pasteur’s discovery of fermentation by investigating the process that yeast used to turn sugar into alcohol. To get under the hood, they cracked open yeast cells and separated the cellular components into two mixtures.

One mixture contained the enzymes needed for fermentation and the other contained several small molecules. Though they didn’t know it at the time, this small molecule mixture contained NAD+. And it was vital for the process of alcoholic fermentation to proceed.

While this discovery helped establish NAD+’s essential role in beer making, it was not quite an anti-aging breakthrough. A deeper understanding of just how crucial NAD+ is to our mitochondria wouldn’t begin for another 40 years. Because like most great discoveries or innovations, understanding the role healthy cells play in aging was a long and non-linear process, with many bumps in the road along the way. 

Chapter 3: Discovering the properties of NAD+.

In 1929, a former art student continued Harden and Young’s work. Hans von Euler-Chelpin studied the details of the reactions that happened during yeast fermentation. In his work, he was actually able to separate the components of this process into their individual parts, essentially “purifying” NAD+. Euler-Chelpin is also credited with uncovering the first insights about NAD+’s chemical shape and properties, laying the foundation for all future research surrounding this vital molecule.

By 1936, Otto Heinrich Warburg had uncovered that NAD+ was an essential part of yet another crucial chemical reaction: hydride transfer. Warburg was also studying fermentation when he realized the hydride transfer process, which is essential to cellular metabolism, used NAD+. Hydride transfers happen any time there’s an exchange of a hydrogen atom and its accompanying electrons. Warburg’s research showed that the N (nicotinamide) which accepts the hydride in NAD+’s molecular makeup was the primary reason this process was able to occur and move forward in the first place. 

Pellagra had disrupted the nation since the early 1900s. This disease, also known as “the black tongue” in dogs, caused symptoms such as dermatitis, diarrhea, and dementia in people of all ages. Although Joseph Goldberger had identified pellagra as a nutritional deficiency, his experiments leading to that discovery were more than controversial. In 1938 Conrad Elvehjem continued this research by conducting his own somewhat controversial experiments and found that nicotinic acid, a form of vitamin B3, cured pellagra in dogs.

Nicotinic acid, also known as niacin, would eventually be used as a vitamin supplement to cure pellagra in humans. But it’s only one example of how vitamins would enhance healthy aging for years to come.

Chapter 4: Connecting vitamins to NAD+.

Today, there are plenty of lists online about the kinds of foods, drinks, or supplements we can take to help our cells acquire these essential vitamins that are vital for preventing diseases like pellagra, scurvy, and rickets. These vitamins prevent these deficiencies by acting as “precursors" for essential cellular molecules.

A precursor is a compound that can create another compound through a biochemical reaction. Vitamin K begins the chain reaction in our cells so our blood can clot, vitamin A kick-starts the nervous system response that gives us sight, and vitamin B begins the process of turning food and drinks into energy. Without these vitamin precursors, our cells can’t perform those basic everyday functions we sometimes take for granted. 

In 1940, Arthur Kornberg drew on the research of those before him to narrow down exactly which vitamins served as precursors to NAD+. He combined Euler-Chelpin’s work of “purifying” NAD+ to its most basic form and Conrad Elvehjem’s discovery that nicotinic acid cured pellagra. He separated NAD+ and recombined it with other isolated components to replicate the chemical reaction he hypothesized was already taking place in our cells. And as such, discovered the first known vitamin precursor to NAD+. 

Chapter 5: Investigating NAD+ more seriously.

After replicating the creation of NAD+, Kornberg’s predecessors attempted to breakdown the process even more. The Preiss–Handler pathway was discovered by two guys named, Jack Preiss and Philip Handler. These two showed that nicotinic acid is converted into NAD+ in three steps, and identified the proteins and enzymes responsible for them.

In 1963, Paul Mandel of the University of Strasbourg’s Institute of Biochemistry further advanced this quest. His work identified a reaction that actually broke NAD+ into two separate parts: nicotinamide and ADP-ribose. Mandel’s findings led biochemists to better understand just how essential NAD+ is to energy metabolism in the cell, and therefore to the mitochondria themselves.

All of these studies may seem rather arbitrary, but each discovery fed into and informed those that followed. These findings would eventually draw modern researchers to the mitochondria as a way to better understand healthy aging. Especially once a group of “longevity proteins” got involved.

Chapter 5: Using sirtuins to study longevity.

At the start of the 21st century, scientists were studying yeast fermentation again. They found some of these seven proteins known as sirtuins were responsible for extending lifespan in yeast. Researchers began to wonder, if sirtuins could expand the life of yeast cells, would they be able to do the same for humans?

Although they still don’t have the clinical trials to support this hypothesis yet, researchers see a lot of promising results in the past studies surrounding yeast and mice. They found some sirtuins affect longevity because they use NAD+ to help keep certain genes “silent,” or non-functional. When sirtuins are active and thriving, these “gene silencers” encourage cellular health in yeast and mice.

Sirtuins and NAD+ work together to:

• Regulate circadian rhythm: The Sirt1 affects gene function, which in turn can help the body’s many circadian rhythms stay in sync.

• Increase energy metabolism: Sirt1 deals in energy metabolism and Sirt3 is an essential part of the citric acid (or Krebs) cycle. Both of which are an integral part of turning food and drinks into energy.

• Maintain a healthy nervous system: NAD+ supports the body’s normal response to inflammation by activating Sirt1.

Whenever we stress our bodies to the point where they need sirtuins, NAD+ goes into overdrive. If we do too many of those things at once or without replenishing those NAD+ levels first, there might not be enough NAD+ to go around. Meaning sirtuins may not have full access to all their resources in order to help us stay healthy. 

Chapter 6: The future of healthy aging.

Age itself is inevitable. Defects are written into our DNA before we’re born. There’s nothing wrong with turning to trustworthy topical treatments to address the outward effects of aging. But if we really want to figure out what’s going on, it helps to remember why we see those signs in the first place: our cells.

Scientists now know that our cells use NAD+. But they’ve also learned that NAD+ levels decline over time and under stress. So everyday things like eating too much and drinking alcohol can deplete our body’s natural NAD+ resources. Basic cellular functions are left to fight over a dwindling supply of NAD+ that only gets smaller as we age.

According to research published in Slate, lifespans have been on the rise for decades. So what are we supposed to do with all this extra time we’re accumulating? With NAD+ supplements in our arsenal, the real question is what are we going to do with all this newly restored health and vitality? The answer from our bodies is clear: Thrive.