Thread by @gregmushen

Longevity is a game of avoiding chronic disease for as long as possible. The more diseases you accumulate over time, the shorter you will live.

Subsistence populations are largely free of chronic disease, and despite wildly different diets, there’s one metric they share 👇

Most chronic diseases are flux issues. If our inputs exceed our outputs, that’s when we start developing disease.

Insulin resistance

For example, insulin resistance (except in genetic disorders) occurs when we are in a chronic energy surplus.

Over time, fat build up in cells (primarily ceramides).

This can happen in muscle, our liver, our fat, etc. but the pattern is the same.

Insulin resistance is therefore mostly a flux problem.

Our inputs are too high relative to clearance.

We don’t clear enough glucose, this gets stored as fat, and over time, we become insulin resistant.

Atherosclerosis is largely the same.

When we ingest lipids, we increase our absolute secretion (there are exceptions).

We clear through reducing secretion and increasing clearance through LDL-R.

This is primarily done with movement, although, statins work the same way.

And once again, there are many genetic patterns that can impair this, such as APOE, APOB R3500Q, etc.

But outside of genetic clearance issues, the rule prevails.

The longer the lipids hang around (residence time), the higher the exposure, and lifetime exposure drives the risk.

The primary reason why subsistence populations are free of chronic disease is due to having flux balance.

The inputs are roughly equal to the output.

This ensures proper clearance, and less storage, so they have extremely low rates of insulin resistance, and heart disease.

This is even true of populations that have extremely high clearance thresholds, such as the Maasai.

They eat up to 100-200g of saturated fat, which increases their clearance requirements.

But they walk 12-16 miles per day, so they can clear most of it.

Despite this, they have some atherosclerosis. It’s just not at a level where their frequently die from it.

The Tsimane on the other hand, have diets lower in saturated fat.

They walk 18k steps per day through hilly jungle terrain.

This is enough for them to meet lipid clearance requirements, and they have the lowest recorded CAC levels ever recorded in a population.

So it’s not that diet doesn’t matter. It does.

It’s just that when diet elements exceed clearance, that’s when people get into trouble.

This can be roughly approximated by a metric called PAL, which stands for physical activity level.

It is a metric of TEE / BMR

TEE = total energy expenditure
BMR = base metabolic rate

Once this ratio is around 2.0, that’s when we see chronic disease drop dramatically.

When members of subsistence populations are moved to cities, we see this ratio drop.

Once it goes below 1.6, that’s when we start to see chronic disease rear its head: insulin resistance, higher blood pressure, etc.

Move them back, these start disappearing.

And we can see this in the chart.

TEE is remarkable consistent amongst populations.

But it’s the physical activity that will drive high PAL.

But this chart is somewhat misleading.

For example, Japan can have a higher PAL despite moderate movement because they have a high protein diet and smaller stature. So they can hit 1.8-1.9 just with this combo.

People in the US on the other hand have higher BMR because they are larger, but are sedentary, which lands them in the 1.6 range.

The larger you are, the more movement you will need to hit clearance requirements.

I’m 184 lbs, so to hit PAL = 2, I’ll need roughly 20k steps a day and a strength training workout because my BMR is higher.

Does it matter how you get there? Probably not.

Elite endurance athletes for example, can maintain an average PAL of 2.5 for the year. This likely is the upper human limit driven by the limits of training load and digestion itself.

But for us mortals, any combo of calorie burn will likely be sufficient.

The physical activity required to achieve this ratio is upstream from popular longevity metrics:

- Low resting inflammation
- High HDL/low ApoB
- Excellent endothelial function
- Vo2max in the upper quartile
- Low fasting insulin and glucose
- Low visceral fat

Outside of genetic issues, if you hit that PAL ratio, it’s almost certain you will hit the ideal metrics for all of these over time.

In my opinion, if you want a simple and single longevity metric, this is the one to track.

Give it a year, and watch your markers improve.

Health = clearance >= input

Longevity = sustained flux balance (PAL ~ 2.0)