David A. Sinclair Quotes

We'd die quite quickly without amino acids, the organic compounds that serve as the building blocks for every protein in the human body. Without them — and in particular the nine essential amino acids that our bodies cannot make on their own — our cells can't assemble the life-giving enzymes needed for life.

The tragedy of the commons is that humans are not very good at taking personal action to solve collective problems. The trick to revolutionary change is finding ways to make self-interest align with the common good. For people to accept widespread biometric tracking in a way that could help us get ahead of fast-moving deadly viruses, they'll need to be offered something they have a hard time seeing themselves without.

In the same way that genetic information is stored as DNA, epigenetic information is stored in a structure called chromatin.

Analog data are superior for this job because they can be changed back and forth with relative ease whenever the environment within or outside the cell demands it, and they can store an almost unlimited number of possible values, even in response to conditions that have never been encountered before.25 The unlimited number of possible values is why many audiophiles still prefer the rich sounds of analog storage systems. But even though analog devices have their advantages, they have a major disadvantage. In fact, it's the reason we've moved from analog to digital. Unlike digital, analog information degrades over time — falling victim to the conspiring forces of magnetic fields, gravity, cosmic rays, and oxygen. Worse still, information is lost as it's copied. No one was more acutely disturbed by the problem of information loss than Claude Shannon, an electrical engineer from the Massachusetts Institute of Technology (MIT) in Boston.

Here's the important point: there are plenty of stressors that will activate longevity genes without damaging the cell, including certain types of exercise, intermittent fasting, low-protein diets, and exposure to hot and cold temperatures (I discuss this in chapter 4).

One of the best ways to visualize this is to think of our genome as a grand piano.13 Each gene is a key. Each key produces a note. And from instrument to instrument, depending on the maker, the materials, and the circumstances of manufacturing, each will sound a bit different, even if played the exact same way. These are our genes. We have about 20,000 of them, give or take a few thousand.14 Each key can also be played pianissimo (soft) or forte (with force). The notes can be tenuto (held) or allegretto (played quickly). For master pianists, there are hundreds of ways to play each individual key and endless ways to play the keys together, in chords and combinations that create music we know as jazz, ragtime, rock, reggae, waltzes, whatever. The pianist that makes this happen is the epigenome.

Youth → broken DNA → genome instability → disruption of DNA packaging and gene regulation (the epigenome) → loss of cell identity → cellular senescence → disease → death.

Today, I can read an entire human genome of 25,000 genes in a few days for less than a hundred dollars on a candy bar–sized DNA sequencer called a MinION that I plug into my laptop. And that's for a fairly complete readout of a human genome, plus the DNA methyl marks that tell you your biological age.

I eat a lot of plants and try to avoid eating other mammals, even though they do taste good. If I work out, I will eat meat. • I don't smoke. I try to avoid microwaved plastic, excessive UV exposure, X-rays, and CT scans. • I try to stay on the cool side during the day and when I sleep at night. • I aim to keep my body weight or BMI in the optimal range for healthspan, which for me is 23 to 25.

Like rapamycin, metformin mimics aspects of calorie restriction. But instead of inhibiting TOR, it limits the metabolic reactions in mitochondria, slowing down the process by which our cellular powerhouses convert macronutrients into energy.20 The result is the activation of AMPK, an enzyme known for its ability to respond to low energy levels and restore the function of mitochondria. It also activates SIRT1, one of my lab's favorite proteins. Among other beneficial effects, metformin inhibits cancer cell metabolism, increases mitochondrial activity, and removes misfolded proteins.21

How does the SIR2 gene actually turn off genes? SIR2 codes for a specialized protein called a histone deacetylase, or HDAC, that enzymatically cleaves the acetyl chemical tags from histones, which, as you'll recall, causes the DNA to bundle up, preventing it from being transcribed into RNA.

What's the upward limit? I don't think there is one. Many of my colleagues agree.14 There is no biological law that says we must age.15 Those who say there is don't know what they're talking about. We're probably still a long way off from a world in which death is a rarity, but we're not far from pushing it ever farther into the future.

WE ARE ANALOG, THEREFORE WE AGE. According to the Information Theory of Aging, we become old and susceptible to diseases because our cells lose youthful information. DNA stores information digitally, a robust format, whereas the epigenome stores it in analog format, and is therefore prone to the introduction of epigenetic "noise." An apt metaphor is a DVD player from the 1990s. The information is digital; the reader that moves around is analog. Aging is similar to the accumulation of scratches on the disc so the information can no longer be read correctly. Where's the polish?

prompting the United States in 1935 to join about twenty other countries that had already instituted a social insurance program. Social Security made moral sense. It made mathematical sense, too. At that time, just over half of men who reached their 21st birthday would also reach their 65th, the year at which most could begin to collect a supplemental income. Those who reached age 65 could count on about thirteen more years of life.32 And there were a lot of younger workers paying into the system to support that short retirement; at that time only about 7 percent of Americans were over the age of 65. As the economy began to boom again in the wake of World War II, there were forty-one workers paying into the system for every beneficiary. Those are the numbers that supported the system when its first beneficiary, a legal secretary from Vermont named Ida May Fuller, began collecting her checks. Fuller had worked for three years under Social Security and paid $24.75 into the system. She lived to the age of 100 and by the time of her death in 1975 had collected $22,888.92. At that point, the poverty rate among seniors had fallen to 15 percent, and it has continued to fall ever since, owing largely to social insurance.33 Now about three-quarters of Americans who reach the age of 21 also see 65. And changes to the laws that govern the US social insurance safety net have prompted many to retire — and begin collecting — earlier than that. New benefits have been added over the years. Of course, people are living longer, too; individuals who make it to the age of 65 can count on about twenty more years of life.34 And as just about every social insurance doomsdayer can tell you, the ratio of workers to beneficiaries is an unsustainable three to one.

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