Lifespan

Why we age and why we don’t have to

health
science
longevity

1 Listen to Lifespan Summary

2 Book Summary: Lifespan by David A. Sinclair

2.1 The Information Theory of Aging: A Loss of Information

David Sinclair proposes a revolutionary idea: ageing is not caused by the loss of genetic (digital) information, like mutations in our DNA. Instead, ageing is a loss of epigenetic (analog) information.

Imagine your genome is a DVD containing the perfect blueprint for a youthful you. Your epigenome is the laser reader that tells the cells which parts of the DVD to play. Over time, the DVD gets scratched. The digital information is still there, but the laser struggles to read it correctly.

  • Digital Information (Genome): The DNA code itself. It is robust and remains largely intact even in old age. Cloning an old animal into a young one proves this data isn’t lost.
  • Analog Information (Epigenome): The system of proteins (like histones) and chemical marks that package the DNA and control which genes are turned on or off. This system is fragile and degrades over time, like scratches on a DVD. This “epigenetic noise” is the primary cause of aging.

2.2 The Survival Circuit: Why We Age

All life inherited a primordial genetic survival circuit. This circuit’s purpose is to shift a cell’s energy from reproduction to repair during times of adversity.

  1. DNA Damage is Constant: Our DNA is constantly being broken by radiation, chemicals, and even normal cell division.
  2. Sirtuins are the Repair Crew: Longevity genes called sirtuins are key epigenetic regulators. Their main job is to maintain cell identity by keeping certain genes silenced.
  3. Distraction Causes Noise: When DNA breaks, sirtuins are called away from their normal duties to help with repairs.
  4. Cells Lose Their Way: Over time, sirtuins don’t always find their way back to their original positions. This relocation causes genes that should be off to turn on, and vice versa. Cells lose their identity, leading to malfunction, senescence (zombie cells), and the diseases we associate with ageing.

This trade-off: short-term survival for long-term functional decline, is the root cause of aging.

Sinclair argues that we should classify ageing itself as a disease. It is the single greatest risk factor for nearly every major illness, from cancer and heart disease to dementia. By treating the root cause (epigenetic information loss), we can prevent and reverse the downstream symptoms (the diseases of ageing).

2.3 Activate Your Longevity Genes: What You Can Do Now

We can activate our body’s natural defences against ageing by introducing beneficial stress, a concept known as hormesis. This puts our longevity genes (like sirtuins) to work without causing lasting damage.

  1. Eat Less Often (Intermittent Fasting): Calorie restriction is one of the most potent ways to boost longevity pathways. Intermittent fasting achieves similar benefits without constant hunger. This activates sirtuins and another pathway called AMPK while suppressing the mTOR pathway, which promotes growth at the expense of longevity.

  2. Eat Stressed Plants (Xenohormesis): Plants produce defence molecules (like resveratrol in red wine) when they are stressed. Consuming these plants can activate our own cellular defences. A diet rich in colourful, slightly stressed vegetables is beneficial.

  3. Exercise, Especially High-Intensity: High-intensity interval training (HIIT) creates a state of low oxygen (hypoxia), which powerfully turns on longevity genes. This boosts NAD levels, improves mitochondrial function, and grows new blood vessels.

  4. Expose Yourself to Cold and Heat: Spending time in temperatures outside your comfort zone activates sirtuins and stimulates the creation of healthy brown fat, which is metabolically active and declines with age.

  5. Avoid Damaging Your DNA: Minimise exposure to unnecessary radiation (X-rays, CT scans), UV light, and chemicals in plastics, smoke, and charred food. Every DNA break is an event that contributes to epigenetic noise.

  • 16:8 Protocol: Restrict your eating to an 8-hour window each day (e.g., 12 PM to 8 PM).
  • 5:2 Diet: Eat normally for 5 days a week and significantly restrict calories (e.g., to 500-600) for 2 non-consecutive days.
  • Skip a Meal: The simplest way to start is by regularly skipping breakfast or lunch.

2.4 Emerging Therapies: The Future of Longevity

  1. NAD Boosters (NMN & NR): Sirtuins require Nicotinamide Adenine Dinucleotide (NAD) as fuel. NAD levels decline by about 50% by middle age. Supplementing with NAD precursors like Nicotinamide Mononucleotide (NMN) or Nicotinamide Riboside (NR) has been shown to reverse aspects of aging in mice, improving endurance, vascular health, and mitochondrial function.
  2. Metformin: This common diabetes drug activates the AMPK pathway, mimicking some effects of calorie restriction. Large-scale studies show it reduces the risk of cancer, heart disease, and dementia.
  3. Rapamycin: Inhibits the mTOR pathway, which is heavily involved in cell growth and aging. It has consistently extended lifespan in every organism tested, from yeast to mice.
  4. Resveratrol: A molecule found in red wine that activates the SIRT1 sirtuin. It improves metabolic health and protects against diseases of aging in animal models.

As we age, some cells enter a “zombie” state called senescence. They stop dividing but refuse to die, instead secreting inflammatory signals that damage surrounding healthy tissue and accelerate ageing. Senolytics are a new class of drugs designed to seek out and destroy these senescent cells, which has been shown to rejuvenate tissues and extend healthspan in mice.

The most groundbreaking frontier is the ability to reset the epigenetic clock. Using a cocktail of genes known as Yamanaka factors, scientists can reprogram adult cells back to a youthful state. In a landmark experiment in Sinclair’s lab, this technology was used to:

  • Regrow damaged optic nerves in mice.
  • Restore vision in old mice with glaucoma.

This demonstrates that the youthful information is not lost, only scrambled. We may one day be able to safely reset the age of our tissues and organs.

2.5 Key Longevity Pathways to Target

  • Sirtuins: Activate with calorie restriction, exercise, NMN/NR, and resveratrol.
  • AMPK: Activate with calorie restriction and metformin.
  • mTOR: Inhibit with calorie/protein restriction and rapamycin.

3 Summary Video

4 Practise

Design your own simple “Longevity Protocol” for one week. The goal is not perfection but experimentation with hormesis.

  1. Fasting: Choose one day to try a 16:8 fasting window. Simply skip breakfast and don’t eat until lunch.
  2. Exercise: On one day, incorporate a short HIIT session. For example: 30 seconds of high-intensity effort (sprinting, burpees, fast cycling) followed by 90 seconds of rest. Repeat 5-8 times.
  3. Temperature: End one of your showers with 30-60 seconds of cold water.
  4. Diet: For one meal, consciously replace an animal protein source with a plant-based one.

Reflect on how you felt. What was easy? What was challenging? This small practice can build the foundation for sustainable lifestyle changes.

5 Learn More

Back to top