Epigenetic Aging: How old is your DNA?
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Time waits for no one. But can we slow it down a bit? Recent discoveries in the field of epigenetics suggest we might be able to. The first hint that such a thing is possible came from the realization that not everyone ages at the same rate. Sure, those dates on the calendar pass at the same rate for everybody, but some people appear to age slower (or faster) than others – with vastly different age-related physical changes and disease risks.
Recognition of this biological quirk has given rise to the concept of biological age – a measure of a person's physiological and functional state. Dr. Steve Horvath, a professor of genetics and biostatistics at UCLA, has found a way to measure biological aging – a "clock" – based on the methylation pattern of an organism's genome. Methylations are biochemical processes that modify the activity of a DNA segment without changing its sequence – a type of epigenetic change.
Episode highlights:
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A person's risk of disease is more dependent on their biological age than their chronological age.
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Epigenetics refers to processes that can affect gene expression without changing the DNA sequence. Methylation is a type of epigenetic change that occurs over a lifetime in a predictable way and can be used to measure biological age.
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The Horvath clock can accurately predict a person's chronological age based on only the epigenetic information in their blood.
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The GrimAge clock can predict the risk and time of onset of cancer, heart disease, and death.
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Certain drugs can reverse a person's epigenetic age, but the effects on biological age are unknown.
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The discovery of an anti-aging drug is on the horizon.
The discovery of a molecular clock, an algorithm called GrimAge, reveals time until death in a statistical fashion.
"As you age, the methylation of your DNA changes in a predictable way — like clockwork. The speed of this ‘epigenetic clock’ is slightly different for everyone — depending on your individual genetics, and to a lesser extent, lifestyle." Click To Tweet
Epigenetic Clocks are based on measuring methyl groups attaching to specific sites along DNA strands, called CpG islands.
But is it the face of the clock or the gears of aging itself? The premise of Dr. Horvath's clocks is truly remarkable: Predict a person's lifespan, based on a set of chemical modifications to their DNA – a sort of molecular "footprint" that reflects the biological life history of the organism. This clock is incredibly versatile, too, accurately predicting a person's chronological and biological ages across multiple cells, tissues, and organs, and even mammalian species. The clocks have widespread application, too, predicting not only the rate at which a person is aging but also their lifespan and healthspan, based on DNA methylation surrogates in their blood.
As it turns out, a person's chronological age and biological age might not match up. The difference between these two ages is known as age acceleration. Evidence suggests that faster epigenetic age acceleration is associated with many age-related diseases.
Findings from a small clinical trial suggest that a cocktail of drugs can reverse methylation, potentially clicking the "undo" button on aging. But the evidence demonstrating that turning back a person's epigenetic age reduces their biological age just isn't there yet. Until it is, we can use epigenetic clocks to learn about how and why we age, especially the processes of aging hidden within our cells.
This video primer explains the basics of epigenetic clocks, the topic of our interview with geneticist and biostatistician Dr. Steve Horvath.
Relevant work
This episode was fiscally sponsored through The Film Collaborative and a grant from a generous anonymous donor.
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A person's risk of disease is more dependent on their biological age than their chronological age.
-
Epigenetics refers to processes that can affect gene expression without changing the DNA sequence. Methylation is a type of epigenetic change that occurs over a lifetime in a predictable way and can be used to measure biological age.
-
The Horvath clock can accurately predict a person's chronological age based on only the epigenetic information in their blood.
-
The GrimAge clock can predict the risk and time of onset of cancer, heart disease, and death.
-
Certain drugs can reverse a person's epigenetic age, but the effects on biological age are unknown.
-
The discovery of an anti-aging drug is on the horizon.
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The physiological age of an organism, a concept based on the observation that similar organisms age at dissimilar rates. Several factors influence biological age, including genetics, lifestyle factors (such as diet and exercise), and environmental exposures. Biological age may differ markedly from one's chronological age, the number of months or years an organism has lived.
A biomarker of aging based on alterations in an organism’s DNA methylation (DNAm) profile. Methylations occur naturally and regulate gene expression. With age, the methylation state of a gene may change. These changes are quantifiable, serving as a means to gauge biological age, which is often different from chronological age. Several variations of epigenetic clocks have been identified. They are generally categorized according to the type and number of tissues used to formulate the calculation, as well as the type of age measured (e.g., epigenetic versus phenotypic). The most widely used clocks include: - HorvathAge, which predicts intrinsic epigenetic age acceleration, a phenomenon in which an organism's aging is influenced by internal physiological factors such as normal metabolism and genetics.[1] - DNAm PhenoAge, which predicts time-to-death among people of the same chronological age, based on biomarkers of age-related disease.[2] - DNAm GrimAge, which predicts lifespan and healthspan, based on DNAm surrogates in blood, including biomarkers of aging and alterations in blood composition.[3]
- ^ Horvath S (2013). DNA methylation age of human tissues and cell types. Genome Biol 14, 10.
- ^ Levine, Morgan E.; Lu, Ake T.; Quach, Austin; Chen, Brian H.; Assimes, Themistocles L.; Bandinelli, Stefania, et al. (2018). An Epigenetic Biomarker Of Aging For Lifespan And Healthspan Aging 10, 4.
- ^ Lu, Ake T.; Quach, Austin; Wilson, James G.; Reiner, Alex P.; Aviv, Abraham; Raj, Kenneth, et al. (2019). DNA Methylation GrimAge Strongly Predicts Lifespan And Healthspan Aging 11, 2.
Genetic control elicited by factors other than modification of the genetic code found in the sequence of DNA. Epigenetic changes determine which genes are being expressed, which in turn may influence disease risk. Some epigenetic changes are heritable.
The process in which information stored in DNA is converted into instructions for making proteins or other molecules. Gene expression is highly regulated. It allows a cell to respond to factors in its environment and involves two processes: transcription and translation. Gene expression can be turned on or off, or it can simply be increased or decreased.
A biochemical process involving the addition or subtraction of a methyl group (CH3) to another chemical group. In epigenetics, a methyl group is added to an amino acid in a histone tail on DNA, altering the activity of the DNA segment without changing its sequence. Under- and over-methylation are referred to as hypomethylation and hypermethylation, respectively.
A chemical that causes Parkinson's disease-like symptoms. MPTP undergoes enzymatic modification in the brain to form MPP+, a neurotoxic compound that interrupts the electron transport system of dopaminergic neurons. MPTP is chemically related to rotenone and paraquat, pesticides that can produce parkinsonian features in animals.
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