STEP ONE
Discover the clinical importance of epigenetic age testing.
START LEARNING HERE
THE RATIONALE BEHIND TESTING BIOLOGICAL AGE
OR CONTINUE TO STEP TWO
Is AGE a
DISEASE ?
OUR THOUGHTS
At TruDiagnostic, we think that the definition of aging as a disease is important for regulatory processes. For instance, Loyal, a company focused on aging interventions for dogs, recently received the first ever FDA formal acceptance that a drug can be developed and approved to extend canine lifespan.
This means that a regulatory pathway with defined criteria might be possible for humans. However, ultimately, whether aging is classified as a disease or not, we irrefutably know that it is a huge risk factor for other recognized illnesses.
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The neighboring graph, for example, shows the top three causes of death in the U.S. in 2020. The relative risk of death caused by aging far exceeds factors like smoking and obesity. Thus, we think quantifying age, especially on a molecular basis, is important regardless.
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What is
BIOLOGICAL
AGING ?
When you think of aging, you may think of some common, outward expressions (phenotypes), such as wrinkles, gray hair, health issues, or limited physical mobility.
These visible traits are reflective of complex, biological processes occurring in your body; processes that are interconnected and occurring at molecular levels all the way down to your DNA.
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The difference in each of our biological "mileage" is the reason why we may look and feel significantly older or younger than others who share the same birth year as us.
Your Chronological Age, or calendar
age, is the number of years that have passed since your birth. This number is fixed and does not change to reflect improvements or declines in health and physical capabilities.
Your Chronological Age, or calendar
age, is the number of years that have passed since your birth. This number is fixed and does not change to reflect improvements or declines in health and physical capabilities.
Your Biological Age, or cellular age, is a calculation of the toll that life has taken on your body, and is a number that can fluctuate based on various lifestyle, environmental, and/or medical influences.
Your Biological Age, or cellular age, is a calculation of the toll that life has taken on your body, and is a number that can fluctuate based on various lifestyle, environmental, and/or medical influences.
Biological Age
EXTENT OF DAMAGE
Chronological Age
EXTENT OF TIME
Biological Age
EXTENT OF DAMAGE
Chronological Age
EXTENT OF TIME
EXPERT
EXPLANATIONS
Dr. Morgan Levine
YALE SCHOOL OF MEDICINE
Dr. Levine investigates the mechanisms of aging, while recognizing that aging processes do not happen at a uniform pace for everyone. Central to her exploration is the concept of epigenetics — the factors that influence gene activity without changing the DNA sequence.
Dr. Levine investigates the mechanisms of aging, while recognizing that aging processes do not happen at a uniform pace for everyone. Central to her exploration is the concept of epigenetics — the factors that influence gene activity without changing the DNA sequence.
Levine focuses on DNA methylation, a significant epigenetic change that occurs with aging, and the development of models called 'clocks' that can be used to predict biological age.
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While she acknowledges that it might be possible to reverse aging at a cellular level, Levine clarifies that the ultimate goal is not to “cure” aging or death, but to delay disease onset and improve healthspan.
How do you
MEASURE
biological aging?
Weight has kilograms, distance has meters, but what unit of measurement captures the extent of cellular aging within your body? There isn't (just) one!
From musculoskeletal to inflammatory biomarkers, there are many phenotypic and microscopic indications of age within the human body.
Aging is extremely complex and is not easily captured by any single diagnostic tool. This means that quantifying aging requires an accumulation, analysis, and interpretation of multi-omic snap shots, in order to see the bigger picture.
In order to quantify the multi-layered, biological 'toll of time' throughout one's body, scientists must...
1. Link chronological age to different biological patterns that can already be quantified (such as telomere length in kilobases, or clinical lab values)
2. Develop a mathematical equation (an algorithm or 'age clock') that examines, filters, and weighs those various age-related measurements, in order to determine the overall, biological age of one's body.
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When it comes to biological patterns that are most predictive of age-related health outcomes, epigenetics has emerged as the strongest biomarker for the job.
Why is
EPIGENETICS
the best?
If it is important to determine biological age to preventatively treat age-related diseases, then it is important that one's biological age calculation is accurately predicting those risks.
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All epigenetic algorithms (clocks) used by TruDiagnostic have the strongest predictive values linked to outcomes of aging and disease, compared to other clocks that are currently in use across the research and diagnostic fields.
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Results generated by our age clocks reflect the impacts of validated aging interventions such as lifestyle, medical, and environmental changes.
Why not measure
by TELOMERE
LENGTH ?
Over the years, telomere length has been the most commonly used biomarker when it comes to testing for biological age. While extensively validated by more than 1,000 studies, the major pitfall of telomere testing rests in its inability to predict age-related disease outcomes.
​
Other disadvantages of telomere testing include:
- Cell types can be confounded.
- Results yield the WORST hazard ratios
(predicted risk of occurrence) to disease.
- Correlation to age is poor.
- The two methods of telomere testing
(qPCR vs FISH) produce very different
results.
- Reliability and consistency of
measurements are poor, with ICC values
(Intraclass Correlation Coefficient)
between 0.6-0.8.
What is DNA
METHYLATION ?
It's the epigenetic biomarker we use to measure biological aging! There are several ways that DNA regulation (epigenetics) can occur in the cells throughout your body, with one of the most prominent methods being DNA Methylation.
DNA methylation is a process where molecules (methyl molecules) attach to sections of your DNA. This process can be thought of as the "turning off" or dimming of the instructions at that gene location.
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Broadly speaking, methylation is not considered good or bad as it pertains to your health and wellness because every gene has a specific function and might need to be turned off or turned on according to individual circumstances.
Understanding
CLOCKS &
ALGORITHMS.
An age clock tells you how old you really are (your biological age), without using your date of birth to make a determination.
Scientists began developing and using mathematical formulas in the early 2010s in order to quantify the various aging processes occurring within the human body. These algorithms are what epigeneticists and researchers call clocks (or epigenetic aging clocks), and they have significantly evolved in recent years.
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It is important to note that not all clocks are equal when it comes to telling you the right time (a precise biological age with accompanying, precise risks of death and disease).
What makes a
DNAm AGE CLOCK reputable & reliable?
01
What generation is the clock, and what was it programed to measure?
A good DNA methylation (epigenetic based) age clock is specifically trained to calculate biological age-based health outcomes; using 2nd or 3rd generation algorithms that account for aging phenotypes.
02
How validated (researched, peer-reviewed, published) and transparent is the clock?
DNA methylation age clocks have 1,500+ validation studies to support the scientific significance of their results generated. Algorithms that use other biomarkers, such as proteomic clocks, have only a handful of validation studies.
03
How precise is the clock?
A good DNA methylation age clock will have a high ICC VALUE (Intra-Class Correlation). A high ICC value (closest to one, on a scale of 0-1) shows that the measuring technique itself is reliable and consistent.
04
How extensively is it correlated with age related health outcomes?
A good DNA methylation age clock will have a significant HAZARD RATIO, aka a highly accurate prediction of disease occurrence in relation to death.
05
Do results respond to validated aging interventions?
We believe that valuable insights should be actionable! A good DNA methylation clock will reflect the results of lifestyle, environmental, or medical changes when a patient retests following the implementation of such aging interventions.
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At TruDiagnostic, we use SIX, peer-reviewed &
PUBLISHED ALGORITHMS (2nd & 3rd generation) to determine your results.
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No competing laboratories currently use any published, 2nd generation algorithms to determine biological aging.
Horvath
(1st Generation)
Hannum
(1st Generation)
GrimAge
(2nd Generation)
PhenoAge
(2nd Generation)
DunedinPoAm
(3rd Generation)
DunedinPACE
(3rd Generation)
Algorithm Trained and Developed to Detect...
Biomarker Criteria #1
Feasible for use in a clinical trial in older adults?
Biomarker Criteria #2
Robustly associated with chronological age across independent cohorts?
Biomarker Criteria #3
Predict age-related change in function, chronic disease, or death?
Biomarker Criteria #4
Responsive to interventions that beneficially affect the biology of aging?
Chronological Age
Chronological Age
Biomarkers, Smoking, Death
Phenotypic Age
Pace of Aging (Change)
Pace of Aging (Change)
When examining HAZARD RATIOS, (the accuracy of prediction of disease occurrence in relation to death), our exclusively licensed DunedinPACE algorithm is worth noting.
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In the charts below, you can see a 64% increased risk prediction when using the DunedinPACE clock, compared to the 2% increase reflected when using the original Horvath algorithm.
