#010 Dr. Aubrey de Grey and Dr. Rhonda Patrick Talk Aging
Dr. Aubrey de Grey, founder of SENS Research Foundation and biomedical gerontologist, discusses preventing and reversing aging by repairing molecular and cellular damage. The conversation covers epigenetics, inflammation, parabiosis, CRISPR, and stem cell technologies.
Deep Dive Analysis
15 Topic Outline
Introduction to SENS Research Foundation and Aging Philosophy
Understanding Aging as Accumulation of Damage
Role of Epigenetics in Cellular Aging and Adaptation
Steve Horvath's Epigenetic Clock and its Implications
Challenges in Translating Aging Research to Therapies
Inflammation as a Double-Edged Sword in Aging
Addressing Inflammatory Damage by Targeting its Causes
Glymphatic System and Molecular Garbage Clearance
Parabiosis Research and Factors in Young Blood
Limitations of Lifestyle Factors in Extending Lifespan
Impact of CRISPR/Cas9 Technology on Gene Therapy
Advances in Induced Pluripotent Stem Cells (iPSCs)
Epigenetic Memory in iPSC Reprogramming
Trade-offs in Aging: Cancer vs. Other Functions
SENS Research Foundation's Mission and Upcoming Conference
7 Key Concepts
Damage (in aging)
Damage refers to the accumulation of various molecular and cellular changes in the body that are inevitable consequences of life. Initially harmless, this damage eventually exceeds the body's tolerance, leading to physical and mental decline, and the diseases of old age.
Epigenetics
Epigenetics is the study of changes in cells that affect which genes are turned on or off, without altering the underlying DNA sequence. These changes can involve DNA methylation, histone modifications, or higher-level chromatin packing, influencing protein expression and cell function.
Epigenetic Noise
Epigenetic noise refers to the amount of variation in epigenetic changes happening at the individual cell level without specific genetic direction. This is contrasted with coordinated epigenetic responses, which are considered adaptations to minimize pathogenic consequences of other age-related changes.
Immunosenescence
Immunosenescence describes the age-related decline in immune system function, where immune cells (like T cells) no longer divide or function optimally. These senescent cells can become detrimental, producing inflammatory substances that damage other cells and contribute to aging.
Glymphatic System
The glymphatic system is a recently discovered brain waste clearance pathway that becomes active during sleep. It involves cerebral spinal fluid flushing out extracellular aggregates, such as amyloid plaques, and other buildup from the brain.
Parabiosis
Parabiosis is a scientific technique where the circulatory systems of two animals (typically a young and an old one) are surgically joined. This allows for the exchange of blood factors, and has shown potential to reverse some biomarkers of aging in older organisms.
Induced Pluripotent Stem Cells (iPSCs)
iPSCs are a type of stem cell that can be generated directly from adult cells, such as skin cells, through genetic reprogramming. These cells are 'pluripotent,' meaning they have the ability to differentiate into any cell type in the body, offering potential for regenerative medicine.
10 Questions Answered
The SENS Research Foundation aims to prevent and reverse aging by developing technologies that can periodically repair the various types of molecular and cellular damage that accumulate and drive the aging process.
The decline in repair capacity is caused by the accumulation of damage that the body cannot repair even when young. This unrepaired damage accelerates the creation of new damage and impedes existing repair mechanisms, leading to an overall decline in function.
Epigenetic changes observed in aging are primarily adaptations, genetically programmed responses by cells to minimize the pathogenic consequences of other non-genetic damage accumulating in the body.
Steve Horvath's epigenetic clock can identify a person's age with 96% accuracy (plus or minus four years) by looking at specific methylation patterns across multiple tissues, though the R-squared is lower (around 70%) when focusing on the adult part of life (23-70/80 years).
Inflammation is a double-edged sword; it is essential for surviving infections and is therefore good for us. However, in aging, the inflammatory response can become maladaptive, exacerbating the accumulation of non-infection-related damage like oxidized cholesterol.
Research using parabiosis (joining circulatory systems of young and old animals) shows that factors in young blood can reverse some biomarkers of aging in multiple organs of older animals, though the specific causal factors are still being identified.
While optimal diet and lifestyle can significantly improve health expectancy and prevent early death (e.g., from obesity), the epidemiological data suggests that even the best lifestyle choices might only extend maximum lifespan by a few years (e.g., around two years, or a four-year difference between USA and Japan's average life expectancy).
CRISPR has dramatically advanced gene therapy by offering incredibly high site specificity and fidelity, meaning it can precisely target and modify genes without significant off-target effects. This allows for higher concentrations of engineered DNA to be used, increasing the proportion of cells modified safely.
Yes, methods have been perfected to induce pluripotency without viruses, such as using messenger RNA or electroporating proteins. While efficiency can be low, these non-viral methods are continually improving.
Standard methods for creating iPSCs do not 100% erase the original epigenetic state, leading to some 'epigenetic memory.' However, refined techniques using more factors can significantly reduce this memory, and research is ongoing to determine how much elimination is necessary for specific therapeutic purposes.
8 Actionable Insights
1. Prioritize Sleep for Brain Health
Ensure adequate sleep to allow the brain’s glymphatic system to actively clear out waste products like amyloid plaques and other extracellular aggregates, which accumulate during aging.
2. Optimize Micronutrient Intake
Consume optimal amounts of essential micronutrients, including minerals and vitamins, as they are crucial for running your metabolism and enabling enzymes that repair damage.
3. Maintain Healthy Lifestyle
Adopt a good diet, specifically eating your greens, and engage in regular exercise. Additionally, avoid excessive drinking and smoking to support overall health, which may extend lifespan by a couple of years.
4. Avoid Obesity
Prevent obesity, as it is strongly associated with a significant reduction in lifespan, potentially ranging from a 7-year to a 14-year reduction.
5. Cautious Inflammation Modulation
In older age (60s-70s), be cautious about dampening or excessively boosting your inflammatory response. A strong inflammatory response is necessary to fight infections, and altering it could increase risks like pneumonia.
6. Support FoundMyFitness
Consider contributing $5 a month to FoundMyFitness via patreon.com/foundmyfitness or foundmyfitness.com to help fund production and enable the creation of more in-depth content.
7. Explore SENS Research
Visit SENS.org (S-E-N-S.org) to learn more about the SENS Research Foundation and its work on preventing and reversing aging through damage repair technologies.
8. Attend SENS Conference
Consider attending the SENS Research Foundation conference in Burlingame from August 19th-21st. Registration is open, and it will cover all aspects of rejuvenation biotechnology with academic and industry participation.
5 Key Quotes
The best way to deal with this is to find a best-of-both-world solution, to let people have the strong inflammatory response that they need in order to be protected well against infections, but to fix the problem of maladaptive activation of the immune response.
Aubrey de Grey
Aging is, you know, it's a side effect of being alive. It's like, it's the consequence of the accumulation in the body of various molecular and cellular changes that are inevitable consequences of what the body does to keep us alive from one day to the next.
Aubrey de Grey
The only way that we're going to bring them under control is by developing a panel of interventions that we can use to periodically repair those various types of damage and thereby leave the overall abundance of damage in the body below that threshold, such that it's harmless.
Aubrey de Grey
When you see a change late in life, you always have to ask yourself, is this change happening as part of aging or is it happening as an adaptation to part of aging?
Aubrey de Grey
CRISPR, on the other hand, started out being pretty good at its site specificity and better than that, as time's gone on, very rapid advances have been made such that now it's just out of site, site specific. It's incredibly high fidelity.
Aubrey de Grey