Can measuring ‘biological noise’ tell us our true biological age?

Generation Lab founders on the science of biological noise and harnessing its potential to prevent the onset of age-related diseases.

Last week, we brought you the news of a new player entering the biological age testing market. Co-founded by renowned aging researcher, UC Berkeley professor Irina Conboy, and backed by the likes of George Church, the launch of Generation Lab caught the eye with its approach of measuring something called “biological noise” to calculate biological age.

Longevity.Technology: The bold claim made by Generation Lab is that its approach measures “actual” biological age, rather than biological clocks, which it says are mathematical model predictors of aging and disease trained on comparing a group people with each other. To put some more meat on the bones of the company’s approach, we caught up with Conboy and one of her co-founders, Alina Rui Su.

Su, who studied longevity at Harvard Medical School and in Conboy’s lab at Berkeley, has some strong views when it comes to biological aging clocks.

“There are a lot of biological clocks out there, and the majority are using a linear prediction model, which is basically guessing your biological age based on a mathematical model,” she says. “Their model is based on aging happening in a linear way, which is not biologically true, so they’re using a model that’s not biologically compliant.”

The art of biological noise

To explain what she means, Su goes back to the early 2000s and Conboy’s seminal paper on heterochronic parabiosis, and more recent research in plasma exchange in mice and dilution of plasma in both mice and humans.   

“By exchanging blood between a young mouse and an old mouse, it was established that the aging process can be reversed, including sustainable changes in proteomics and DNA methylation,” she says. “And that tells us aging is not happening a linear way. If it was, you’d be getting one grey hair per day throughout your life!”

“Rather than predicting like everybody else, our approach is based on biological evidence – we’ve developed the first ever measurement tool to measure biological noise in your body.”

Can measuring ‘biological noise’ tell us our true biological age?
Generation Lab founders (L-R) Michael Suswal, Irina Conboy and Alina Rui Su.

Generation Lab’s approach uses a “noise detector” to measure changes in a group of cytosines (a component of our DNA) that are expected to remain unchanged throughout our lives. The dysregulation of these cytosines – or noise – is hypothesized to be an accurate biomarker of aging and disease, and Conboy’s research in this area was the cover story in the September issue of Aging last year.

“Essentially, biological noise is a predictor of health,” says Su. “Before your body enters a disease stage, like Alzheimer’s or diabetes, it starts sending out signals indicating that the expression of specific genes is becoming noisier. These signals can be detected through defined molecular changes and that’s why we believe that biological noise is a key biomarker of aging and disease.”

The relevance of biological noise in aging is not new. It had been observed for many years in different experimental systems that organisms, tissues, cells, and sub-cellular processes become stochastically dysregulated – noisier – as they age. However, Conboy says that, before the discovery made in her lab at UC Berkeley, it was not known how to accurately quantify the noise, or to use it to detect disease or as a biomarker of aging.

Measuring noise throughout the body

The noise detector developed by the Conboy Lab, and employed by Generation Lab, is looking for noise across multiple mechanisms in the body.

“It could be that your epigenetics and DNA methylation and/or proteome, metabolome become noisier,” says Conboy. “Basically, there are molecular disbalances in your body – gene expression, enzymes and proteins, which precipitate tissue degeneration and loss of function that can be identified by specific changes in specific pathways related to aging.”

“We can measure those signals and see if you are on a trajectory of becoming unhealthy – or if you are stable or even improving.”

Can measuring ‘biological noise’ tell us our true biological age?
Generation Lab’s biological age test measures aging risk factors across 20 biological systems in your body.

From a simple cheek swab sample, Su says that Generation Lab can observe the health trajectories of multiple organs and biological systems in the body, with the aim of being able to help you take action before disease potentially sets in.

“Our noise detector detects the biological noise in your body, which directly reflects the molecular disbalance at that point, for both the body as a whole and for specific functions,” she adds. “And if you are going in a direction that might become a problem, let’s try to correct it.”

Enabling informed actions

The output of a Generation Lab test essentially provides a risk score for around 20 different biological systems, measuring everything from the respiratory, cardiac, and digestive systems to things like inflammation, metabolism, and tissue regeneration. Each system is given a “biological age” as well as an overall score for the individual, but Su explains that the age number isn’t the important thing to focus on.

“The main thing is to understand what your main aging risk factors are, and this will be different from person to person,” she says. “Where are you aging, where are you performing better, and, most importantly, what do you need to do based on this? The goal is to avoid accelerated aging and keep all your systems in a stable, healthy state for as long as possible.”

When it launches next month, Generation Lab will offer a yearly subscription-based model, starting at around $400, with packages including either three or six tests per year. In addition to consumers, the company is also targeting longevity clinics and concierge health providers.

“Our tool can help doctors understand more about how the data can provide actionable insights – are the things that they’re prescribing actually working?” says Su, who reveals that Generation Lab already has 12 clinical partners signed up, including New York regenerative medicine clinic Eterna Health.

“We can provide a clear indication of the trajectory of one intervention compared to another.”

After taking a test, users will receive a telehealth session with their clinic to go over the results. Su explains that, while the initial advice provided to people who take the test will be relatively simple, this will become more specific and personalized over time.

“I’m not saying that we’ll be able to tell you how to reverse aging right away,” she says. “But, as the clinics accumulate more and more proprietary innovative data sets, the suggestions will be tailored better for everyone.”

“We’re agnostic about what is happening on the prescription side of things,” adds Su. “It’s up to the clinician to decide what interventions to suggest, if any. But what we can provide is a standard measurement to know the changes in biological noise of specific functions of the body, so the clinician can act having better information.”

Building a biobank for aging

Looking to the future, Generation Lab aims to build something akin to a biobank for aging that will be made available to all.

“Anyone working in longevity will be able to use this dataset to predict more precisely what is working and what’s not, and what are the potential targets for antiaging medicines,” says Su. “We want to help the entire industry by building this center of measurement – whether for companies trying to develop medicines or insurance companies trying to develop plans based on health rather than disease.”

This data could become available as early as 2025, after the company has assembled enough datasets to provide a longitudinal sample base.

“Generation Lab data are the numbers of person’s actual (not predicted) biological age,” says Conboy. “When quantified for different individuals over time this allows informed directionality on the fundamental process of aging, and enables designing safe and feasible approaches for aging reversal and disease prevention.”