Aeon goals

Humans are somewhat like semelparous species – species that perish after reproducing. Instead of dying immediately, we begin to decline.

Here's the basic life cycle:

- Development: This is when humans are growing up, from babies to young adults.
- Adult Phase (Sexual Maturity): After growing up, humans reach a point where their bodies are mature and can have children. During this phase, the body doesn't grow much anymore and tries to maintain its functions.
- Senescence: Eventually, the body begins to experience age-related decline, marked by a deterioration in its functions and changes in certain biological markers.

By looking at specific biomarkers in our bodies, we should be able to tell when each of these transitions occur. These transitions are the foundation of the nature of aging and are the most important thing to understand.

We can use the natural variance in human biomarker data to understand the nature of aging. If 20% of the people go through these transitions at a slower rate, our initial hypothesis is that those 20% have delayed sexual maturation which will show up in sexual maturation biomarkers. We should be able to use sliders to ‘chop off’ causal biomarker sections of the population and see a significant shift in the start of senescence.

How do we determine sexual maturation biomarkers?
By first coming up with a panel for reproductive aging biomarkers.

But there is a challenge – observe the estradiol graph below.

Estradiol is a hormone that varies too much during a woman's menstrual cycle to be a clear indicator of where she is in the aging process. This makes it tough to use this hormone to understand aging using currently available data. There are ways of fixing this graph to be more like a curve than a field of dots.

The goal for Aeon Biomarkers is to develop a set of these biological signs that can help track the aging process more accurately. The first step toward curing human senescence is to have solid data for a panel of reproductive aging biomarkers.

Aging is not a disease.

When we are young children, we age to become healthy adults. To declare aging as a disease essentially declares life itself as a disease.

But later in life, for reasons that we still don’t fully understand, our bodies deteriorate, decline, and as time passes, this decline worsens.

I was ready to invent new terminology for this stage when I remembered that we already have a scientific word to describe it, and that word is 'senescence,' introduced in 1891 by Charles Sedgwick Minot at the Physiological Laboratory of Harvard Medical School in a paper titled 'Senescence and Rejuvenation.'

But there is a paradox here.

Senescence also plays a crucial role in wound healing and other beneficial processes. When cells become senescent in response to damage or stress, they often aid in tissue repair and wound healing. So, an organism might have cells undergoing senescence for beneficial reasons, like wound healing, while still being generally healthy and not in a state of overall deterioration. Without a nuanced understanding, treatments aimed at combating senescence could inadvertently impair beneficial processes.

Over the last century, senescence has become more associated with cells rather than whole organisms. This perspective shift has left a void in the effort to understand senescence at the level of the organism. Under what conditions would one declare a person to be senescent?

The differentiation between aging, beneficial senescence, and detrimental senescence is a longstanding problem in longevity. Our mission is to recognize and distinguish these different motifs using biomarker information.

Defining aging biomarkers

At Aeon, our first step in the process is to define what constitutes an aging biomarker. We follow two simple rules to guide our approach toward identifying them:

- Anything that changes with age is a part of aging.

- Aging happens to everyone.

These two simple rules will set the tone for the company’s approach toward aging biomarkers. Consider the following scatterplots of HDL vs LDL cholesterol for a population of roughly 100,000 individuals.

These two graphs clearly show different patterns of age related change. HDL cholesterol appears to stay at the same level across the entire human lifespan while LDL cholesterol changes. HDL cholesterol is not an aging biomarker – LDL cholesterol is.

The fact that everyone ages makes it easier to declare which biomarkers are associated with aging. Age related changes must be happening across the entire human population. The way Aeon determines this is through floating point mean and median values.

The black dots represent floating point median values for every age, while red dots represent floating point mean. The close association of these two values to each other at every age indicates these changes are happening for everyone, not just a pathogenic subpopulation. Any biomarkers that change with age for everyone are aging biomarkers.

Announcing Aeon Biomarkers

Today we are announcing Aeon Biomarkers, a recently formed company with the mission to redefine aging. Our goal is to identify and analyze aging biomarkers, helping preventative healthcare companies measure and enhance the effectiveness of their therapies/interventions in the fight against aging.

Here is how everything started:

I’ve been in the longevity space for quite a long time, and the field is evolving rapidly. But even though so many companies are discovering new therapies to fight aging and diseases altogether, I noticed that we still couldn’t answer a simple question: Which biomarkers change with age?

If we don’t know the answers to why things happen, how can we possibly solve the aging problem at a systemic level? I first built Agerank with publicly available data about biomarkers. Even with these data, the findings were astonishing. There are so many secrets yet to be revealed and explained about why our body ages and why diseases develop as we get older.

More questions began to emerge from the findings - why doesn’t HDL cholesterol change with age, but LDL cholesterol does? Why does Diastolic blood pressure change differently than Systolic blood pressure? Why do Cystatin, a kidney damage biomarker, and Troponin, a heart damage biomarker, have the exact same life-change pattern? There is a large gap in basic knowledge about the fundamental nature of aging.

A few months ago, I met Katerina Stroponiati at a longevity conference and discussed this gap, and we agreed that If we don’t know what to measure, how can the field move to the next level?

Katerina became the first investor, and Aeon Biomarkers was formed.
In the coming weeks, we will unveil more details about it.