Insulin and aging – a disappointing relationship (Paper)

Experimental studies in animal models of aging such as nematodes, fruit flies or mice have observed that decreased levels of insulin or insulin signaling promotes longevity. In humans, hyperinsulinemia and concomitant insulin resistance are associated with an elevated risk of age-related diseases suggestive of a shortened healthspan. Age-related disorders include neurodegenerative diseases, hypertension, cardiovascular disease, and type 2 diabetes. High ambient insulin concentrations promote increased lipogenesis and fat storage, heightened protein synthesis and accumulation of non-functional polypeptides due to limited turnover capacity. Moreover, there is impaired autophagy activity, and less endothelial NO synthase activity. These changes are associated with mitochondrial dysfunction and oxidative stress. The cellular stress induced by anabolic activity of insulin initiates an adaptive response aiming at maintaining homeostasis, characterized by activation of the transcription factor Nrf2, of AMP activated kinase, and an unfolded protein response. This protective response is more potent in the long-lived human species than in short-lived models of aging research resulting in a stronger pro-aging impact of insulin in nematodes and fruit flies. In humans, resistance to insulin-induced cell stress decreases with age, because of an increase of insulin and insulin resistance levels but less Nrf2 activation. These detrimental changes might be contained by adopting a lifestyle that promotes low insulin/insulin resistance levels and enhances an adaptive response to cellular stress, as observed with dietary restriction or exercise.

Open Access Paper:


In know that many “dream” of having a continuous insulin meter and think Peter Attia has said that he’d see that as more valuable than continuing our glucose meters.

In that context, it was very interesting to see that what causes insulin spikes is not always the same thing as causes glucose spikes…

See for instance

The insulin index of food represents how much it elevates the concentration of insulin in the blood during the two-hour period after the food is ingested. The index is similar to the glycemic index (GI) and glycemic load (GL), but rather than relying on blood glucose levels, the Insulin Index is based upon blood insulin levels. The Insulin Index represents a comparison of food portions with equal overall caloric content (250 kcal or 1000 kJ), while GI represents a comparison of portions with equal digestible carbohydrate content (typically 50 g) and the GL represents portions of a typical serving size for various foods. The Insulin Index can be more useful than either the glycemic index or the glycemic load because certain foods (e.g., lean meats and proteins) cause an insulin response despite there being no carbohydratespresent, and some foods cause a disproportionate insulin response relative to their carbohydrate load.

Holt et al.[1] have noted that the glucose and insulin scores of most foods are highly correlated,[2] but high-protein foods and bakery products that are rich in fat and refined carbohydrates “elicit insulin responses that were disproportionately higher than their glycemic responses.” They also conclude that insulin indices may be useful for dietary management and avoidance of non-insulin-dependent diabetes mellitus and hyperlipidemia.


Above from: Insulin index - Wikipedia

Might be worth looking into / discussing this more.

1 Like

It seems like many lifespan extending interventions target insulin in some way:

    1. Acarbose: anti-diabetic
    1. Metformin (weak effect and only in male mice): anti-diabetic
    1. Canagliflozin: anti diabetic
    1. 17 alfa estradiol: improves glucose control
    1. Caloric restriction: lower insulin because of not eating
    1. Glycine: improves glucose control
    1. Taurine: improves glucose control

Also, in male mice anti diabetics work much better than in female mice (where it has almost no effect)


I understood the insulin effect of protein was related in part to opening the doorway of cells to amino acids. But since insulin also triggers uptake of blood glucose, the pancreas also releases glucagon to cause the liver to release glucose to keep blood sugar stable.

Thanks for posting! It’s not a “disappointing relationship” for me. Luckily, I have a very low insulin level. My insulin level after an eggs & bacon breakfast was only 2.
The downside is that I find I eat a lot, and at very exact times, or I become very irritable.
The other downside I read about was that people with low insulin are more prone to develop dementia. :scream_cat::scream_cat:
So not all good news…


“Experimental studies in animal models of aging such as nematodes, fruit flies or mice have observed that decreased levels of insulin or insulin signaling promotes longevity. In humans, hyperinsulinemia and concomitant insulin resistance are associated with an elevated risk of age-related diseases suggestive of a shortened healthspan.”
And that is why we never really know, without extensive trials, that the mouse data will transfer to humans.
I am of course a believer in rapamycin, but even that might be hopemium.


Sorry I don’t understand how the part you cited leads to this statement, can you help me understand?

Yeah, I think you read it wrong “decreased levels of insulin or signaling promotes longevity” Then about humans “hyperinsulinemia and insulin resistance shortens healthspan”. They say the same thing.

1 Like

DrT, mine is pretty low too at 1.7 fasting per my last labs. I’m a little overdue for repeat labs so I’ll check it again. You are the first person to describe my exact experience of feeling like I need to eat often/regularly and it seems like I require quite a bit of food for my size. I’d love to understand this better!

Hi blsm,

As I understand it, insulin is what transports glucose from the blood into the cells. If your insulin levels are very low, there simply may not be enough to go around and, if blood glucose levels decline, you get symptoms of low glucose (weakness, sweaty, spots on vision, headache etc).
Basically, people like us are very close to Type-1 diabetic territory, without actually being Type-1 diabetics. I have always been this way and so is my sister, (she carries barley sugar in her handbag) so I suspect it has a genetic basis.


Thank you so much sir, that makes perfect sense. I’ve had times in the past when I ate more refined carbs (ex.white rice) or even a bowl of instant oatmeal by itself and I’d often have reactive hypoglycemia. I seem to be good now as long as my carbs are from fibrous veggies or dairy. It’s fortunate yet odd that figured out what worked for me years ago but never understood why until now. Thanks again!

@blsm and @DrT your (and my) low fasting insulin might actually be good from a longevity / almost CR like phenotype

if you have concerns, have you tried wearing a continuous glucose meter (CGM) for a few weeks and see whether you have abnormal glucose spikes?

your fasting insulin does not say whether your pancreases is able to ramp up insulin to modulate (and your bodies muscles take in) glucose from food

for that a CGM or for the direct insulin response curve a oral glucose tolerance tests (OGTT) is needed
Glucose tolerance tests: What exactly do they involve? - - NCBI Bookshelf(OGTT,enough%20by%20the%20body’s%20cells.


Yeah. I tried intermittent fasting for 5 years. 1 meal per day on 3 days per week. It was horrible! I was constantly irritable, weak, grouchy; you name it.
I realise now that I’m probably always near the edge of CR and trying IF on top just about pushed me over!
I’ve never been a smoker nor drug addict…but I think for me, food comes close! LOL.


@Neo, thank you for the CGM suggestion. You are the second person to mention that to me so I should probably take it seriously! I have a glucometer that I’ve been using for several months doing waking, pre and post meal checks as part of a class I’m taking called Data Driven Fasting. All is good except for when I eat something like beans and rice together which will spike me into the 160’s. I’ve been learning more about how I personally need to eat to avoid large spikes and rapid drops but I still get hungry and need to eat every 3-5 hours. Thank you again for pointing me toward using a CGM to get more data.

1 Like

That’s only true if your body does not produce ketones as a substitute for the lack of sugar.
I always run in the morning in a fasted state and sometimes on long trail runs (15k to half marathons) the glucose goes as low as 50mg/dl or less and I only notice it when I look at the GCM.
Took me 6 months to 1 year to be totally adapted to a low carbs diet but it has been worthwhile for me.
I don’t need any of those gels and race nutrition planning at all. Just burning my own fats.

When I start the run the glucose goes up as the liver makes more of it.
After 15 to 20 minutes the muscles have warmed up, capillaries are dilated, mitochondria are producing energy, etc. and the glucose goes down to between 50 and 80 ml/dl
Finally after the reaching a glucose low, the liver makes more of it and the glucose level goes up to 90~100 mg/dl.

I definitively recommend using a GCM. Each person is different and some of the findings with a GCM were surprising to me.