Biomarkers of aging

Body temperature would seem to have an almost intuitive connection to lifespan. One of the original theories of aging was a metabolic one: the faster an organism burns, the sooner it burns out. Therefore a higher body temperature would correlate with a lower lifespan. In humans, this turns out to be the case.

Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans

Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women (mean age 53.7±9.4 yrs) consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western diets. The CR and EX groups were significantly leaner than the WD group. Energy intake was lower in the CR group (1769±348 kcal/d) than in the WD (2302±668 kcal/d) and EX (2798±760 kcal/d) groups (P<0.0001). Mean 24-hour, day-time and night-time core body temperatures were all significantly lower in the CR group than in the WD and EX groups (P≤0.01). Long-term CR with adequate nutrition in lean and weight-stable healthy humans is associated with a sustained reduction in core body temperature, similar to that found in CR rodents and monkeys. This adaptation is likely due to CR itself, rather than to leanness, and may be involved in slowing the rate of aging.

The study found that leanness that resulted from calorie restriction – but not leanness that resulted from exercise – was correlated with low body temperature.

The chart above shows the correlation between body fat percent and core temperature. The article also contains this statement: “In the Baltimore Longitudinal Study of Aging (BLSA) men with a core body temperature below the median lived significantly longer than men with body temperature above the median in the absence of CR [8].”

The study referred to is this one: Biomarkers of Caloric Restriction May Predict Longevity in Humans. The study notes three important biomarkers that are associated with longer life in calorie-restricted animals, body temperature (lower), plasma insulin levels (lower), and DHEA levels (higher). Then – here’s the interesting part – they looked at these biomarkers in aging humans, and plotted these against their survival curves. Results below:

biomarkers of aging

What you see here is that in humans, who were not calorie restricted, lower body temperature and insulin, and higher DHEA levels, correlated with survival.

So, calorie restriction changes levels of these three important biomarkers, and in turn these biomarkers are correlated with longevity, even in the absence of calorie restriction.

For longer life, one wants to keep these biomarkers at levels that correlate with longevity. An easier, and probably all around better way to do this than calorie restriction is through intermittent fasting, which has virtually the same effects on these markers as calorie restriction, with the added advantage (and it’s a big one) that you don’t feel like you’re starving yourself all the time. Intermittent fasting will keep insulin levels and body temp lower, and DHEA levels higher.


Leave a Comment:

sabril says November 23, 2014

Eyeballing the charts, it looks to me like if everything works reasonably well, calorie restriction is likely to buy you an extra 3-5 years. Agreed?

    P. D. Mangan says November 23, 2014

    Not sure if you can come to that conclusion from the charts, I’ll have to think about that. No ages are listed for one thing, it’s cumulative survival. However, others have come to your conclusion elsewhere. The amount CR extends life may be related to the amount of life effort put into reproduction, e.g. rodents, who use a great amount of life energy on reproducing might get an extra 40% longer life from CR. That’s very unlikely to be the case with humans.

SJ says November 24, 2014

P. D, great article.

What’s the best email address to get in touch with you? Would like to talk re: your new book.



The Myth says November 24, 2014

Score! I consistently read between 96 and 97.5 as my average body temp. Curious of the mechanism through which fasting causes DHEA to increase. Nice post.

    P. D. Mangan says November 24, 2014

    I guess you’re going to live a long time. My body temp is also quite low.

nightboat2cairo says November 24, 2014

I ran really cold for a decade or two. Usually in the 96s. I’ve caused digital thermometers to error at the doctor’s. 97 was a rarity. Longevity be damned, it was a big problem. Winters are cold and so was I. I switched my diet from being low carb for 6 years to adding in rice, potatoes and more gut friendly veggies and my temp increased to normal for the first time that I can remember. I cheered the first time I scored a 98. Way, way more healthy now, way more active, sleep way better.

    P. D. Mangan says November 24, 2014

    I’d be the first to admit that being cold isn’t great fun. Just some speculation here, if adding carbs makes your temp go up, then it raises insulin levels too, 2 of the 3 markers of aging noted above. This may be one aspect of the fundamental trade-off between growth and longevity. I need to write more on that, but basically anything that causes growth puts a dent in lifespan. Centenarians typically have low mTOR activation and low insulin levels, as well as low levels of thyroid hormones.

Anon says November 26, 2014

RE: DHEA, I’ve been wondering about that one…

I started supplementing DHEA about May of this year largely based on this post, along with a couple other things I’d read here and there:

I didn’t feel any acute problem needing addressed, but was feeling myself slowing down a bit and being in the 40-45 demo, thinking it was probably age-related.

I started taking 50mg/day. At first I didn’t notice any difference, but after a month or two I began noticing, shall we say, a distinct, yet not overwhelming, libido-surge a few hours after taking the supplement. It seemed to last 30-60 minutes before subsiding. I decreased my dosage to 25mg/day. The surge dropped intensity, but there was still a distinct reaction from the supplement.

So, it makes me wonder about risk factors on DHEA and prostate health. Anyone see anything on that?

More generally, it’s one thing to take various growth supplements when one is in his late 60’s and 70’s. It seems another to take them in one’s 40’s and 50’s. Especially if the supplements are going to be a fixed part of one’s diet, what does 20 years of DHEA supplementing to do one’s health? Do those thoughts ever occur to you? How have you reconciled them?

Finally, anyone else taking DHEA that they would like to comment on any effects they’ve experienced? Thx.

    P. D. Mangan says November 26, 2014

    DHEA at one time was going to be the fountain of youth, but interest seems to have waned. I can only speculate that that’s because other things work better? The linked article said that not only did those taking DHEA have “a remarkable increase in perceived physical and psychological well-being”, but increased IGF-1 levels – a growth hormone. My guess is that the sense of well-being and IGF-1 levels are related. I’ve taken DHEA myself before, but it seems to give me a pronounced case of acne, so I don’t anymore.

      Anon says November 28, 2014

      Thanks Dennis. Interesting about the acne. Haven’t noticed that any. Oddly enough, I do get acne from wheat.

      Anyone else tried or currently taking DHEA?

    mike says June 8, 2015

    I can say I’ve noticed the same libido surge. Now, based on your comment, I think I’ll experiment with the timing aspect to see if I can better synch with my wife’s best libido time frames.

nightboat2cairo says November 26, 2014

It seemed like too many years of low-carb and it went downhill. Hungover (often with vomiting) every morning on no alcohol intake. Sleeping every afternoon. Waking up every night at 3am. Inability to breathe through my mouth. Exhausted with a limited ability to do work.

After about a year and a half of trying various things I fixed it, but without knowing what specifically did it. This is part of the reason why your blog is fascinating, since you overcame something similar and are working to improve things further. Your post on supplements was excellent.

Current diet is not too different, just has more rice and potatoes and prebiotic veggies in it than before. Headaches rare and milder, sleep better, breathe better, work harder, way better ability to deal with cold, ill a lot less. Body temp is still below normal but I have hit 98 at least once.

Forcing my body temperature lower than it is right now is not a good thing. It is more complex than “lower is better “, but I’m sure you know that.

Joshua says January 30, 2015

This does kind of confirm something I’ve noticed for a while — intermittent fasting or just restricting calories generally seems to lower my body temperature. This sucks in winter, as I end up feeling cold all the time. But, it seems there may be some benefit from it. This is reinforcing my idea that summer is the perfect time for fasting — get lean, look good at the beach, reap health/longevity benefits….and feel a little cooler.

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