David Sinclair: Extending the Human Lifespan Beyond 100 Years | Lex Fridman Podcast

David Sinclair is a geneticist at Harvard and author of Lifespan.

This Podcast is a repost which originally appeared on lexfridman.com
Podcast notes are a repost which originally appeared on PodcastNotes
Lex Fridman Podcast #189 with David Sinclair - June 6, 2021
Edited for content and readability - Images sourced from Pexels

Key Takeaways

  • Wearables have the potential to revolutionize medicine
  • The goal is doctors being able to look at a dashboard of our body based on swabs, blood tests, and biosensors and make real-time, tailored recommendations
  • Top causes of aging: broken chromosomes, cell stress, smoking
  • Lifestyle methods to slow aging: fasting (skip 1-2 meals per day), eat more vegetables and less red meat, exercise, get good quality sleep (quality more important than quantity)

Introduction

Dr. David Sinclair (@davidsinclair) is a biologist, professor of genetics at Harvard, author, and expert on aging and longevity. His research and biotech companies focus on understanding why we age and how to slow its effects.

In this episode of the Lex Fridman Podcast, Lex and guest David Sinclair discuss the determinants of why we age, solving aging, the trend of wearables and tracking health data, artificial intelligence, social perspectives of lifespan , and death, and lifestyle factors to improve lifespan.

Host: Lex Fridman (@lexfridman)

Book: Lifespan: Why We Age and Why We Don’t Have To by David Sinclair

Artificial Intelligence & Immortality

  • We live in a time we can leverage data to have the pieces of the life of people we can gather using technology, beyond just written books
  • AI makes it possible to bring back people that we love in some way and in essence achieve immortality
  • AI can be used to build experience, thoughts, speech
  • AI uses in aging: generate biological clocks, predict protein folding, assemble genomes, predict longevity in mouse in response to stimuli, diagnosing a virus

David Sinclair Interest And Predictions On Wearables

  • Wearables represent the merging of machines and humans  
  • Wearables help us collect biological data about our bodies
  • We can use data to keep ourselves in optimal shape
  • “Picture a future where you’re monitored constantly so you wouldn’t have a heart attack, you’d know that was coming.” – David Sinclair
  • It’s feasible that wearables and similar technology will indicate what antibiotic or medication to take, what to eat, etc. – and augment physicians who would just need to sign off on the protocol
  • COVID-19 accelerated biological technologies & medical advances
  • There will be day doctor’s use wearable technology to send patients home for monitoring instead of keeping them in the hospital
  • Wearables will revolutionize medicine – it can collect data which can be used to predict sickness, diagnose disease

InsideTracker

  • InsideTracker: David Sinclair co-founded a company that creates personalized and actionable plans to help people optimize their bodies through nutrition, supplements, and lifestyle
  • Connects scientific papers to individual data and make recommendations for lifestyle
  • InsideTracker leverages hundreds of thousands of human data points and thousands of scientific articles to create a formula of what works and what doesn’t for your body
  • Recommendation of food and nutrition was better than leading drug at treating type 2 diabetes
  • Soon, the current model of medicine is going to outdated as machines and data will know us better than our doctor
  • “We wouldn’t drive a car without a dashboard so why would doctors do the same?” – David Sinclair

How And Why We Age

  • Aging is both a feature and bug of evolution
  • We only need to live as long as we need to in order to replace ourselves – some breed slowly and build a body that lasts, some breed quickly and die quickly
  • We can do better at aging
  • Hallmarks of aging include: loss of telomeres, senescent cells, loss of energetics
  • Defining factor of aging: preservation of information and loss of entropy
  • “Loss of information in our bodies is a root cause of aging.” – David Sinclair
  • We have information regulator genes in our bodies – upregulation could preserve health
  • Information in cells = DNA and epigenome
    • DNA is usually intact in animals and humans over time
    • Epigenome: regulators of genetic information
  • Question of importance: is there a repository of information in the body to restore from?
  • Antagonistic pleiotropy: a system built to keep us alive when we’re young but has damaging effects later in life
  • Causes of aging: (1) broken chromosomes and (2) cell stress – smoking also dramatically accelerates biological age
    • It’s hard to repair something that’s constantly breaking: we have 1000 chromosome breaks per day – the break is recognized by proteins and is usually fixed but not always
  • You can slow down aging using three embryonic genes to reset the age of tissues to a certain point – but if you don’t do it right it can cause tumors  

Data Sharing In Biology

  • “We’re living through what’s going to be seen as one of the biggest revolutions in human health through the gathering of data about our bodies.” – David Sinclair
  • Ultimately, we’re all going to be monitored
  • There will be a reversal where blamed will be assigned for not collecting data
  • Decisions are made based on very few tests when we have the opportunity to collect more
  • Consumer health is going in the direction of the patient having access to better data than the doctor (through private lab tests, biotech companies, etc.)
  • Doctors are becoming excited and interested about seeing and using privately collected patient data to make more informed decisions
  • The U.S. currently spends 17% of GDP on healthcare – we can save money by monitoring using wearables and prevention
  • Ideally, we can create a system where we can share data as we’d like and keep what we wouldn’t

Lifestyle Methods To Slow Aging

  • Fasting is one of the oldest ways to improve health – we need to optimize how long and the frequency
  • “If there’s one thing I can recommend to anybody to slow down aging it’s to skip a meal or two a day.” – David Sinclair
  • Note: David Sinclair is a big fan of one meal a day; the carnivore diet has made Lex feel really good
  • When you eat seems to be more important than what you eat
  • Data says plant-based foods are better than meat-based foods
    • People who live longer tend to eat Mediterranean diets with little red meat
    • High meat consumption stimulates mTor
    • Could take rapamycin to counteract effects of meat
    • Meat produces immediate health benefits (muscle, energy) but potentially at the expense of long term effects
  • Eat a diet full of leafy greens, avoid spikes in sugar, possibly explore supplementing with resveratrol
  • Exercise clearly extends longevity
  • You don’t need much exercise to get great benefit – exercise aerobically a few times per week (even 10 minutes) and lift weights a few times per week
  • Sleep is critical for longevity to avoid premature aging and adverse health outcomes
  • Sleep quality seems to matter more than quantity
  • The brain is the center for longevity so we have to take care of stress levels, mental health

Data Collection Methods

  • We’ll likely work to moving away from blood draws for data
  • Currently: swab and ship to the lab to test hormones, stress levels, blood glucose, etc.
  • In the next 10 years: spit on paper and stick in a machine for analysis
  • Home tests are really easy and scalable if they can become democratized (price reduced)

Realistic Goals Of Lifespan

  • If you start eating cleaner in your 20s, that has been shown to improve lifespan in animal models
  • If you are in your 20s, aim to reach 100
  • There’s no maximum limit to human lifespan

Death & Denial

  • We seem to draw meaning from life being rooted in our existence – most of us find it distressing to face our own mortality
  • All living beings have evolved to want to live and survive
  • It’s possible we evolve to naturally deny aging because we need to use our energy and focus for innovation and life instead of death
  • It might be easier to be lazy if you are immortal

Note: Wearable Oura ring was referred to multiple times throughout the show

How mRNA and DNA vaccines could soon treat cancers, HIV, autoimmune disorders and genetic diseases

The idea of using genetic material to produce an immune response has opened up a world of research and potential medical uses far out of reach of traditional vaccines. Deborah Fuller is a microbiologist at the University of Washington who has been studying genetic vaccines for more than 20 years. We spoke to her about the future of mRNA vaccines.

Below are excerpts from that conversation which have been edited for length and clarity.

This article is a repost which originally appeared on The Conversation
Deborah Fuller - January 6, 2022
Edited for content and readability - Images sourced from Pexels

Our Takeaways:

  • Nucleic acid vaccines are based on the idea that DNA makes RNA and then RNA makes proteins.
  • These vaccines are effective at inducing a T cell response.
  • For cancer, the goal is to make your body better able to recognize the very specific neoantigens the cancer cell has produced and destroy it.
  • For autoimmune disorders, the vaccine would suppress the T Cells to keep the immune system from attacking myelin

How long have gene-based vaccines been in development?

This type of vaccine has been in the works for about 30 years. Nucleic acid vaccines are based on the idea that DNA makes RNA and then RNA makes proteins. For any given protein, once we know the genetic sequence or code, we can design an mRNA or DNA molecule that prompts a person’s cells to start making it.

When we first thought about this idea of putting a genetic code into somebody’s cells, we were studying both DNA and RNA. The mRNA vaccines did not work very well at first. They were unstable and they caused pretty strong immune responses that were not necessarily desirable. For a very long time DNA vaccines took the front seat, and the very first clinical trials were with a DNA vaccine.

But about seven or eight years ago, mRNA vaccines started to take the lead. Researchers solved a lot of the problems – notably the instability – and discovered new technologies to deliver mRNA into cells and ways of modifying the coding sequence to make the vaccines a lot more safe to use in humans.

Once those problems were solved, the technology was really poised to become a revolutionary tool for medicine.

What makes nucleic acid vaccines different from traditional vaccines?

Most vaccines induce antibody responses. Antibodies are the primary immune mechanism that blocks infections. As we began to study nucleic acid vaccines, we discovered that because these vaccines are expressed within our cells, they were also very effective at inducing a T cell response. This discovery really prompted additional thinking about how researchers could use nucleic acid vaccines not just for infectious diseases, but also for immunotherapy to treat cancers and chronic infectious diseases – like HIV, hepatitis B and herpes – as well as autoimmune disorders and even for gene therapy.

How can a vaccine treat cancers or chronic infectious diseases?

T cell responses are very important for identifying cells infected with chronic diseases and aberrant cancer cells. They also play a big role in eliminating these cells from the body.

When a cell becomes cancerous, it starts producing neoantigens. In normal cases, the immune system detects these neoantigens, recognizes that something’s wrong with the cell and eliminates it. The reason some people get tumors is that their immune system isn’t quite capable of eliminating the tumor cells, so the cells propagate.

With an mRNA or DNA vaccine, the goal is to make your body better able to recognize the very specific neoantigens the cancer cell has produced. If your immune system can recognize and see those better, it will attack the cancer cells and eliminate them from the body.

This same strategy can be applied to the elimination of chronic infections like HIV, hepatitis B and herpes. These viruses infect the human body and stay in the body forever unless the immune system eliminates them. Similar to the way nucleic acid vaccines can train the immune system to eliminate cancer cells, they can be used to train our immune cells to recognize and eliminate chronically infected cells.

What is the status of these vaccines?

Some of the very first clinical trials of nucleic acid vaccines happened in the 1990s and were for cancer, particularly for melanoma.

Today, there are a number of ongoing mRNA clinical trials for the treatment of melanoma, prostate cancer, ovarian cancer, breast cancer, leukemia, glioblastoma and others, and there have been some promising outcomes. Moderna recently announced promising results with its phase 1 trial using mRNA to treat solid tumors and lymphoma

There are also a lot of ongoing trials looking at cancer DNA vaccines, because DNA vaccines are particularly effective in inducing T cell responses. A company called Inovio recently demonstrated a significant impact on cervical cancer caused by human papilloma virus in women using a DNA vaccine.

Can nucleic acid vaccines treat autoimmune disorders?

Autoimmune disorders occur when a person’s immune cells are actually attacking a part of the person’s own body. An example of this is multiple sclerosis. If you have multiple sclerosis, your own immune cells are attacking myelin, a protein that coats the nerve cells in your muscles.

The way to eliminate an autoimmune disorder is to modulate your immune cells to prevent them from attacking your own proteins. In contrast to vaccines, whose goal is to stimulate the immune system to better recognize something, treatment for autoimmune diseases seeks to dampen the immune system so that it stops attacking something it shouldn’t. Recently, researchers created an mRNA vaccine encoding a myelin protein with slightly tweaked genetic instructions to prevent it from stimulating immune responses. Instead of activating normal T cells that increase immune responses, the vaccine caused the body to produce T regulatory cells that specifically suppressed only the T cells that were attacking myelin.

Any other applications of the new vaccine technology?

The last application is actually one of the very first things that researchers thought about using DNA and mRNA vaccines for: gene therapy. Some people are born missing certain genes. The goal with gene therapy is to supply cells with the missing instructions they need to produce an important protein.

A great example of this is cystic fibrosis, a genetic disease caused by mutations in a single gene. Using DNA or an mRNA vaccine, researchers are investigating the feasibility of essentially replacing the missing gene and allowing someone’s body to transiently produce the missing protein. Once the protein is present, the symptoms could disappear, at least temporarily. The mRNA would not persist very long in the human body, nor would it integrate into people’s genomes or change the genome in any way. So additional doses would be needed as the effect wore off.

Research has shown that this concept is feasible, but it still needs some work.