What is aging?
We all know what aging is, as we experience it firsthand in ourselves and those around us. But what is aging, scientifically speaking?
Aging occurs when physiological changes take place that result in a decline of the cells’, organs’, and by extension, organism’s biological functions and its ability to adapt to its environment and its metabolic processes.
The aging process is mediated by twelve biological processes, such as epigenetic alterations, DNA damage and cellular senescence.
Age is just a number.
Recently, scientists have definitively proven what we knew all along: some people age more quickly or slowly than others. Although two people may be the same chronological age, one may be significantly younger – or older – than the other, biologically. Contrary to popular belief, for most of us this difference is predominantly based on lifestyle factors over genetics, by as much as fourfold (80% lifestyle, 20% genetics).
The difference in one’s biological rate of aging is powerfully depicted in the image below. A group of scientists created composites of photographs of people all aged 45 chronologically. However, the first composite for both the male and female is of the 10 biologically youngest 45 year olds (according to the DunedinPACE epigenetic clock; more on this clock below!). The second image is a composite of the 10 subjects who are biologically closest to the mean; these are “average” aging 45 year olds. And, the third image is the 10 biologically oldest, according to DunedinPACE.
The difference between the biologically youngest 45 year olds compared to the biologically oldest is a stark contrast; an external reflection of internal epigenetic, cellular and organismal aging; and a powerful illustration of the power we have when we make a deliberate decision to embark upon a scientifically informed NOVOS Longevity Journey.
Why is biological age important?
Biological age is of greater importance than chronological age because it is the primary risk factor for the majority of chronic illnesses that we’re all susceptible to, ranging from most forms of cancer, to dementia, cardiovascular disease, metabolic disorders, glaucoma, sarcopenia and so on. Further, your biological age is involved in your overall energy levels, cognition, ability to perform physical activities, and how you physically look.
But perhaps what makes biological age most important – and empowering – is that we all have the ability to favorably change it via lifestyle alterations, including diet, supplements and prescriptions, activity, recovery, environment, psychology & relationships. On the other hand, chronological age is immutable.
How can we measure biological age?
When it comes to measuring biological age, dozens of discoveries and technological innovations have taken place over the past decade. In fact, multiple forms of biological age clocks exist, with varying degrees of accuracy and precision, ranging from epigenetic tests, to clocks that measure glycans (note: not glycation), the transcriptome, proteome, metabolome, microbiome, AI that evaluates perceived facial age and more.
Of all the biological age clocks produced to date, one clock within the latest generation of epigenetic tests has proven itself to be the most accurate and promising (more on this below).
What are epigenetic tests?
Epigenetic tests look at the methylation sites of our DNA. Specifically, methylation determines which genes are turned on and off. Patterns emerge in the epigenome as we age, which scientists have been able to leverage for increasingly accurate algorithms that produce biological age clock outputs.
How do epigenetic tests compare to blood tests my doctor orders?
Compared to traditional blood labs that your doctor may run for you to assess deficiencies, excesses or warning signs correlated with diseased states, the latest generation of epigenetic clocks are proving to be more accurate at assessing overall disease and mortality risk across populations.
Whereas blood labs can offer helpful clues for pinpointing specific issues like excess iron or blood glucose, high LDL cholesterol, systemic inflammation or liver or kidney stress, epigenetic tests provide a more holistic view of your overall health, disease and mortality risk, and how you are aging compared to the average person of your chronological age. By offering a single numerical output, they significantly reduce the complexity for assessing your biological state of health when compared with other biomarkers.
Which epigenetic tests exist and which is best?
In 2011, a team of researchers led by Steven Horvath at UCLA produced the first epigenetic clock based on human saliva, which had an average accuracy of 5.2 years. This and other first generation clocks were intent on achieving outputs that were as close to the subject’s chronological age as possible. Since then, second generation clocks have emerged, which incorporate additional environmental variables (e.g., smoking) to be better able to output biological age and by extension, mortality risk.
The latest, third generation of epigenetic clocks includes the DunedinPACE clock, widely considered by industry experts to be the most accurate and actionable of all epigenetic clocks to date.
About the DunedinPACE Epigenetic Clock
A joint effort between researchers at Columbia University and Duke University, DunedinPACE has been calibrated based on blood samples from a cohort of approximately 1,000 participants in a long-term, multi-decade health study known as “The Dunedin Study.”
Using the data obtained from this cohort, the team developed an algorithm named “DunedinPACE” (PACE stands for Pace of Aging Computed from the Epigenome). This algorithm identifies people with an accelerated or slowed rate of aging based on a single blood test.
Whereas all other epigenetic clocks focus on a biological age output, the DunedinPACE clock instead provides a pace of aging: a rate that a person is aging per chronological year (i.e., 0.90 implies 10% slower aging than average, while 1.05 implies 5% faster aging).
The researchers used a machine-learning technique called elastic-net regression to go through data on more than 400,000 different DNA methylation marks to select the ones that were were captured in their Pace of Aging measure. The analysis pulled out a set of 173 methylation marks that, together, measured the rate of aging for individuals at one point in time.
cardiovascular, metabolic, immune, dental, and cognitive biomarkers.
Image: Disparities in the pace of biological aging among midlife adults of the same chronological age
have implications for future frailty risk and policy. Nature Aging, 2021
People with faster DunedinPACE have an increased risk of dying. Specifically, within 7 years from testing, those with a faster than average rate of aging are at a 56% increased risk of death. Further, those with a faster DunedinPACE baseline were at an increased risk for a new chronic disease. Specifically, within 7 years from testing, those with a faster rate of aging are at a 54% increased risk for diagnosis of a chronic disease.
Individuals with faster DunedinPACE experienced higher levels of chronic disease morbidity, which was measured as the count of diagnosed diseases (hypertension, type-2 diabetes, cardiovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and cancer).
The opposite is also true: individuals with slower DunedinPACE results have lower risks of morbidity and mortality.
Why Pace of Aging is the ultimate measure
Determining a precise biological age (note: not a rate of biological aging) for an individual, as opposed to for a population, has proven to be a challenge. When later generation biological clocks are applied to populations (dozens or hundreds of people), the results average out to a relatively accurate biological age across the group. That is, the overestimates are offset by the underestimates. However, when applying the clock and looking at an individual level, the accuracy is not quite as reliable.
Further, a biological age, as opposed to a rate of biological aging, is challenging to change. This makes sense: our biological age is based on decades of accumulated environmental and metabolic damage. Undoing or slowing the rate at which the damage accumulates can take years before showing significant progress.
On the other hand, the DunedinPACE clock’s rate of aging is not only more accurate and precise, it’s also more actionable because it responds to interventions more rapidly. This makes sense: changing your speed is quicker and easier than altering your total distance traveled.
This means that if you make changes to lifestyle factors, including diet, supplements, prescriptions, activities, recovery, stressors, alcohol use, etc., you will be able to see the impact on your aging process more quickly and more precisely with DunedinPACE than alternatives.
How quickly? It can take as little as three months, though we recommend you give it twelve months, for reasons we explain in the section titled, “How do I use NOVOS Age?”
What about telomere length and how does it relate to aging?
Telomere length – the DNA-protective end caps of chromosomes – was once considered to be a promising candidate for determining one’s biological age. Part of the reason for this is that telomere length shortens with each cell division and trends downward with chronological age.
However, researchers have found that the variance for telomere length is too wide when assessed by age and even mortality, and therefore, it’s not considered an accurate biological age clock.
With that said, researchers have found that short telomeres can increase the risk for illnesses including digestive cancers, and when telomeres get too short, mortality rates increase significantly.
Fortunately, there are ways to protect and even lengthen telomeres (via telomerase). In fact, certain supplements can both protect and lengthen telomeres. NOVOS Core includes multiple, safe ingredients that do so, including micro-dosed lithium, magnesium malate and pterostilbene.
Ultimately, telomere length is a relevant biomarker when it comes to holistically tracking your overall health and aging process, it’s just not a reliable biomarker to base an age clock on.
Introducing NOVOS Age
NOVOS Age is the best offering on the market for you to get a firm understanding of your own aging and to equip you on your Longevity Journey. After all, you can’t improve what you can’t measure!
NOVOS Age is composed of three tests:
- DunedinPACE – the primary emphasis of NOVOS Age and your Longevity Journey, this test provides you with your current rate of aging. Created by Columbia University and Duke University researchers, and supported by more than 45 studies at 30 research labs across the world, DunedinPACE is the most accurate epigenetic test available with an ICC score > 0.96. It is also not a corporate “black box” algorithm, as many commercial tests unfortunately are.
- Biological Age – though less accurate and actionable than DunedinPACE, this epigenetic test, collaborated on with Harvard scientists, satisfies a common curiosity: What is my biological age?
- Telomere Length – a biomarker you can use to confirm that your telomeres are not too short, and to track the rate at which they shorten or lengthen based on your interventions
Additionally, NOVOS Age provides in-depth details about the tests as well as actionable insights to improve your score.
NOVOS Age vs. Other Biological Age Clocks
| Attribute | NOVOS Age Clock | Saliva-based Clock by Celebrity Scientist's New Startup | Other tests |
|---|---|---|---|
| Tissue Collection | Blood from a small poke of a finger, a method that is more accurate than via saliva | Saliva from a cheek swab, a method that is generally not very accurate | Blood collection methods that are invasive and far more uncomfortable that via small pokes of fingers |
| Sample Size | Samples from more than 20,000 humans | Samples from more than 8,000 humans | Samples typically from fewer than 2,500 humans |
| DNA Methylation Technology | Built using the modern MethylationEPIC array that measures 850,000 DNA sites and tests your sample on that same technology | Built using the modern MethylationEPIC array that measures 850,000 DNA sites but does not test your sample on that same technology | Built using older arrays that only capture 27,000-450,000 DNA sites |
| Chronological Age Range | 8-102 years | 18-100 years | Less expansive age range often lacking individuals 90+ years of age |
| Diversity | Significant diversity across ethnicity, race, and sex, all supported by many peer reviewed publications | Diversity across ethnicity, race, and sex, but without support of peer reviewed publications | Insufficient representation across ethnicity, race, and sex and without support of peer reviewed publications |
| Test Reliability | Optimized to be reliable across repeat measurements, with published and peer reviewed best-in-class ICC values (accuracy) >.96 for all three algorithms | Claims of being optimized to be reliable across repeat measurements without disclosing ICC values | Exhibit high test-retest error rates |
| Model Type | 3rd generation (latest) clock, the only one trained on longitudinal analysis (people across their lifetimes), the best way to track biological age as shown in publications and tested via peer review | Self-claimed "novel" method-based model that lacks publications, peer review, and head-to-head comparisons against other clocks | 1st generation (oldest) model trained to simply estimate chronological age instead of biological aging |
| Outputs and Analysis | Three: 1) 3rd generation Pace of Aging via DunedinPACE, 2) Biological Age, and 3) Telomere Length | One: A less accurate output of biological age | A single, less accurate output of biological age |
| Creators of Clock | A top team of Duke University and Columbia University scientists with peer reviewed publications | A start up company without publication of the algorithms, thus lacking scientific scrutiny | |
| Number of Studies | 45+ published studies by 30+ longevity scientists' labs across the world | Zero published studies | |
| Immune Cell Controls | Published and Patented Advanced 12-cell immune deconvolution methods (cell changes won't impact accuracy, which is common in saliva and makes blood samples better) | No controls | No controls |
| Studies that prove accuracy in different ethnic groups | Algorithms validated in the Family and Community Health Study of African American Families study, MESA (Multi-ethnic Study of Atherosclerosis), Cebu Longitudinal Health and Nutrition Survey (CLHNS Phillipines), Northern Finland Birth Cohort 1966 Study, Health and Retirement Study, the Normative Aging Study, the Framington Heart cohort, TILDA (the Irish Longitudinal Study of Aging), and many more. | No studies | No studies |
| Studies that show relatonship to outcomes | Algorithms have been validated in the Health and Retirement Study, the Normative Aging Study, the Framington Heart cohort and more. | No studies | No studies |
| Studies that show change with validated anti-aging interventions | The only algorithm proven to respond in a significant way to validated anti-aging interventions such as caloric restriction (Published in Nature) | No studies | No studies |
| Include Clinical Covariates | 21 clinical covariates and telomere length | No clinical covariates | No clinical covariates |
| Comparisons to other algorithms | Comparisons in the FHS study and in the Health and Retirement Study show superior results | No published comparisons | No published comparisons |
| Shares actual data on precision (ICC values) | See ICC values with comparisons in the FHS study. | No data | No data |
You can learn more about what makes NOVOS Age objectively the best biological age clock on the market here.
How do I use NOVOS Age?
We recommend that you first use NOVOS Age at the start of your Longevity Journey. This way, you can track your progress from longevity-minded interventions by testing again after enough time passes.
If you’ve already begun your Longevity Journey, it’s not too late. Benefits from interventions, which are reflected in your epigenome, take time to manifest and can increase with time and self-discipline. Plus, wouldn’t it just be good to know where you currently stand on your pace of aging, biological age and telomere length?
How much time should you wait between tests? DunedinPACE can begin showing changes in as little as three months. Biological age takes longer to show changes beyond the test’s margin of error, possibly twelve months or longer.
We recommend waiting twelve months between tests – no more and no less – not just because of the time it takes to move the needle for biological age results, but for the effects of seasonality on lifestyle.
Our lifestyles change significantly across the span of the year, whether we’re conscious of it or not. Stress, caloric intake, types of foods, alcohol consumption, sun exposure and vitamin D levels, exercise, sleep patterns and circadian rhythms, stress, vacations and more, all differ according to the time of year. For example, many, if not all, of these factors will change for you if you compare your lifestyle during the week preceding the New Year, compared to mid-Summer.
In an effort to reduce confounding factors that can impact your score, we recommend that you take the NOVOS Age test on the same day, week and month as your previous test.
Furthermore, we encourage you to complete the survey that we will email to you after you order NOVOS Age, which is an assessment of your current lifestyle. This will provide a lot of valuable context around your test results when you look back on it and compare it to your future tests’ results.
What else can I do to track my biological age?
To further strengthen your confidence in your results, consider using at-home biotrackers like the Oura Ring, Whoop wristband, Apple Watch, Withings scale and others, to collect age-correlated outputs like pulse wave velocity, heart rate variability, and VO2 max.
You can also track your perceived facial age and how it changes over time, based on an AI technology trained on a dataset of more than 12 million people’s photos. Just make sure you use identical conditions (lighting, angle, camera, etc.).
Finally, you can also track blood biomarkers to make sure they’re all within healthy ranges, especially those related to inflammation (hsCRP, interleukins), metabolism (HbA1c, LDL to HDL ratio), and iron (hemoglobin, ferritin, etc.), which you want as low as possible without going too low.
Get started with NOVOS Age today!
Imagine setting an aggressive weight loss goal, but not having a scale or mirror to track your progress. Although you might be effectively losing weight, you wouldn’t know for certain or to what degree.
A longevity journey is all the more difficult to track. Although you may subjectively look or feel better, biological changes mediated by lifestyle interventions are usually not apparent to us until months or years have elapsed.
NOVOS Age enables you to measure the impact that your lifestyle changes have on your biological health and aging, and equips you with the knowledge needed to confidently continue on your path or make adjustments as needed.
As a once yearly expenditure, we highly recommend that you consider incorporating NOVOS Age into your longevity journey, and complement it with NOVOS Core and Boost – the first set of formulations designed to simultaneously address the 12 causes of aging, backed by world-renowned longevity scientists.
1) Rate of aging via the DunedinPACE epigenetic clock, developed by Columbia University and Duke University scientists. This is the primary emphasis of NOVOS Age
2) Biological age according to an epigenetic clock collaborated on by Harvard scientists
3) Telomere length, which protects your DNA and shortens with age
