Controlling Your Destiny: Epigenetics and Longevity
Why We Aren't Doomed From Birth
Epigenetics is a term that, at first glance, might seem daunting, but it can be demystified with a simple analogy. Derived from the Greek prefix "epi-", which means "over" or "above," it refers to changes that influence gene activity without altering the underlying DNA sequence. Imagine our DNA as a detailed architectural blueprint for a building. While the blueprint itself doesn't change, epigenetic modifications act as annotations, or post-it notes, stuck onto this plan, providing additional instructions or tweaks.
The intriguing relationship between epigenetics and longevity has been a focus of scientific inquiry for years. The origins of epigenetics can be traced back to observations involving identical twins. Although twins share the same DNA, they often exhibit differences in health, susceptibility to diseases, and even aging patterns. This fascinating phenomenon hinted at the presence of factors beyond mere genetic codes that dictate our biological trajectories.
The twin study, titled Epigenetic differences arise during the lifetime of monozygotic twins, published in Proceedings of the National Academy of Sciences of the United States of America (PNAS) in 2005, explored global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins.
To understand their findings, it's essential to grasp the concepts of methylation and acetylation—two primary mechanisms by which DNA undergoes molecular modification. Methylation, for instance, is pivotal in processes like X-chromosome activation, gene silencing, and genomic imprinting. On the other hand, acetylation, especially of histones, typically facilitates gene expression. This modification is crucial for processes like gene activation, DNA repair, and chromosome condensation. To put it succinctly, while methylation generally downregulates gene expression, acetylation upregulates it.
Recent research has only deepened our understanding of this relationship. Among the various epigenetic markers, DNA methylation patterns stand out in their association with biological age. To clarify, while chronological age refers to the number of years since one's birth, biological age is a more nuanced measure, reflecting how old one's body feels or functions.
Over the course of our lives, certain epigenetic markers, like those methylation patterns, can accumulate. These patterns are akin to a patina that forms on a piece of antique furniture, revealing clues about its age and history. In our bodies, these epigenetic shifts influence how genes are expressed or “read.”
The relationship between epigenetics and human longevity has been an active area of research over the past few decades. Some key findings and research studies have included Dr. Steve Horvath at the University of California, Los Angeles, and his work on DNA methylation age of human tissues and cell types.
Dr. Horvath developed a method to estimate biological age based on DNA methylation patterns. His “multi-tissue predictor,” now known as an “epigenetic clock” proposed that “DNA methylation age measures the cumulative effect of an epigenetic maintenance system,” and that its “age prediction, referred to as DNAm age, can be used as a biomarker for addressing a host of questions arising in aging research and related fields.”
Other research includes Dr. Elizabeth Blackburn’s work, who received the Nobel Prize in 2009 for her work on telomerase (an enzyme that replenishes telomeres), and her colleagues have shown that shorter telomeres are associated with various age-related diseases.
Another study by Melissa A. Suter and and Kjersti M. Aagaard-Tillery entitled Environmental Influences on Epigenetic Profiles “highlight seminal studies that implicate in utero exposures as causative agents in altering not only the epigenome of the exposed gestation, but that of subsequent generations.” We’ve also explored how diet affects epigenetics and longevity in this newsletter. Interventions like caloric restriction have been shown to influence lifespan in various organisms.
The concept of "epigenetic therapy" is also emerging. Epigenetic therapy aims to reverse age-related epigenetic changes. Such interventions might not only target age-related diseases but could potentially extend healthy lifespan. Altos Labs, an innovative research lab funded by Jeff Bezos, is working to transform medicine with cellular rejuvenation therapy.
Epic Bio, a South San Francisco-based startup, is “developing therapies to dynamically control gene expression and treat complex disease,” led by CRISPR pioneer Lei Stanley Qi. While these therapies are still in the early stages of development and still require rigorous testing, they inspire great promise in the minds of the world’s leading biogerontologists.
While these studies and findings offer promising insights into the epigenetic factors influencing human longevity, it's essential to note that much of this research is preliminary. Many findings from animal models might not directly translate to humans due to the complexities of human biology and environment. However, the evolving field of epigenetics holds significant promise for unveiling strategies to promote healthy aging and potentially extend human lifespan.
So, how do these epigenetic changes come about? Various external and lifestyle factors play a role. Diet, for instance, isn't just about caloric intake or maintaining weight. What we consume can influence our epigenetic markers. Stress, too, has a pronounced effect. Chronic stress can expedite certain epigenetic changes, potentially accelerating the aging process. The environment we inhabit—whether we're exposed to pollutants, our level of physical activity, and even our social interactions—can leave epigenetic imprints that influence our longevity.
Biologically, there are also changes to consider related to age, such as DNA methylation patterns that can change predictably with age in many individuals. This is how Dr.s Morgan Levin and Steven Horvath were able to create such accurate predictors of biological and chronological age.
It’s also the case that transcriptional programs related to epigenetic reprogramming are plausible. Over time, certain genes are upregulated while others are downregulated due to both intrinsic and extrinsic factors, and this could be driven by a predetermined transcriptional program. However, the exact mechanisms and the extent to which this is pre-programmed versus driven by environmental factors remain areas of active research.
Continuing with the analogy of genes as a musical instrument, consider our genes as keys on a grand piano. The structure and potential of these keys remain consistent, but the tune they produce can vary based on the pianist's touch and style. Epigenetics, in this case, would be the nuances and styles introduced by the pianist, influencing which keys are pressed, with what intensity, and in which sequence. These variations create a melody, or in biological terms, the expression of our genes and our ensuing health and age.
To understand the importance of epigenetics is to appreciate the intricate balance between nature and nurture in our biological narrative. While we inherit a certain genetic code, the story of our health, aging, and longevity is co-authored by epigenetic influences. This idea is sometimes called The Baldwin Effect, and one to which I’ve come to subscribe. Named after the psychologist James Mark Baldwin, who first discussed this concept in the late 19th century, the Baldwin Effect theorizes a link between individual learning and evolutionary adaptation.
Remember, epigenetics concerns heritable changes in gene expression that don't involve alterations to the underlying DNA sequence. These epigenetic changes can be influenced by environmental factors, experiences, and behaviors. When considering the Baldwin Effect in light of epigenetics, one might speculate that learned behaviors or adaptations that cause epigenetic modifications could eventually influence genetic evolution. Your parents might not necessarily be your destiny.
In conclusion, the tapestry of human life is woven with both genetic threads and epigenetic embroidery. As science continues to explore this relationship, we inch closer to understanding the determinants of a long, healthy life. With the promise of epigenetic research, we may soon have the tools to modify the patterns of aging, providing a clearer path to longevity.