Mice Have Longer Lives If Taking Bodybuilding Supplement

[BillTre]

TL;DR Summary

Female mice given alpha-ketoglutarate live longer, show fewer signs of aging.

As someone who is getting old, this caught my eye: News article in Science here.

Alpha-ketoglutarate, a bodybuilding supplement and part of the Krebs cycle (AKA tricarboxylic acid or TCA cycle), prolongs the life of female mice. The Krebs cycle is an energy generating metabolic pathway conserved in almost all life forms.

Experience from its use for medical purposes and by body builders indicates it has few medical problems, unlike other proposed anti-aging treatments.

In the new study, Gordon Lithgow and Brian Kennedy of the Buck Institute for Research on Aging and colleagues turned to mammals. They gave groups of 18-month-old mice (about age 55 in human years) the equivalent of 2% of their daily chow as AKG until they died, or for up to 21 months. AKG levels in blood gradually drop with age, and the scientists’ aim was to restore levels to those seen in young animals.

Some differences jumped out within a few months: “They looked much blacker, shinier, and younger” than control mice, says Azar Asadi Shahmirzadi, a postdoc at the Buck Institute who did the experiments as a graduate student. In addition, the AKG-fed mice scored an average of more than 40% better on tests of “frailty,” as measured by 31 physiological attributes including hair color, hearing, walking gait, and grip strength. And female mice lived a median of 8% to 20% longer after AKG treatment began than control mice, the group reports today in Cell Metabolism.

The AKG-eating mice did not perform better on tests of heart function or treadmill endurance, however, and the tests did not include cognitive performance.

A single chemical making up 2% of a diet seems like a lot to me. However, I am not a dietician.
Its effects may result from reduced inflammation.

Reduced caloric intake has been shown to prolong lives in test animals, but humans have found this difficult to maintain long term.
Other compounds have shown anti-aging effects but can have adverse effects on health:

rapamycin suppresses the immune system and may promote diabetes.

Plans to test humans are underway.

Kennedy, now also at the National University of Singapore, plans to test AKG in human volunteers soon. Looking at a group of people between the ages of 45 and 65, his group will see whether the molecule improves aging-related biomarkers such as inflammation, arterial hardening, and a type of chemical signature on DNA associated with aging.

 

[PeroK]

Steroids for Algernon!

 

[Doc Al]

 

[jim mcnamara]

Krebs cycle intermediates (KCIs) are reported to function as energy substrates in mitochondria and to exert antioxidants effects on the brain. The present study was designed to identify which KCIs are effective neuroprotective compounds against oxidative stress in neuronal cells. Here we found that pyruvate, oxaloacetate, and α-ketoglutarate, but not lactate, citrate, iso-citrate, succinate, fumarate, or malate, protected HT22 cells against hydrogen peroxide-mediated toxicity.

A paper on oxidative stress:
Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384184/

Oxidative stress is cell damage which is controlled by so-called anti-oxidants - like succinyl-CoA in the diagram above in the @BillTre post. Oxidative stress mediated comorbidities (Like type II diabetes) are also known to have to negative effects on Covid-19 patients.

 

[gleem]

A single chemical making up 2% of a diet seems like a lot to me. However, I am not a dietician.

Would the metabolism rate have anything to do with this number, mice having a higher rate than humans?

 

[jim mcnamara]

@gleem @BillTre If you eat the normal Western Diet, then yes, your diet may have way more than 2% (of calories) of something.

Sugar (disaccharride of fructose and glucose), soybean oil (where linoeleic acid predominates), fructose (Corn syrup) are among the top contenders for that award.

Most prepared foods (like frozen XYZ dinner, where XYZ can be almost anything edible: baked goods, potato chips, TV dinner) will contain one, two, or all three of those nutrients. Just read the label.

You can look up the per capita consumption figures for these and other dietary things. I'd guess you won't like it...
Example:

https://www.dhhs.nh.gov/dphs/nhp/documents/sugar.pdf: Average per capita consumption of sugar: 152lb/yr.
Let's use 400g per day, cause I'm lazy, times 4Kcal/g of sucrose is 1600 calories per day. Oh my.

 

[hutchphd]

Ya got to have the song:

 

[russ_watters]

https://www.dhhs.nh.gov/dphs/nhp/documents/sugar.pdf: Average per capita consumption of sugar: 152lb/yr.
Let's use 400g per day, cause I'm lazy, times 4Kcal/g of sucrose is 1600 calories per day. Oh my.

Sorry, but did you skip the lb-kg conversion there? 200g? (189) Not that 800 cal/day would be awesome or anything...

 

[docnet]

A paper on oxidative stress:
Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384184/

Oxidative stress is cell damage which is controlled by so-called anti-oxidants - like succinyl-CoA in the diagram above in the @BillTre post. Oxidative stress mediated comorbidities (Like type II diabetes) are also known to have to negative effects on Covid-19 patients.

Interesting, thanks for posting this.

Neurodegenerative diseases such as Lewy body Dementia and Parkinsons are thought to be caused by reactive oxygen species generated by ox-phos. Scientists don't yet know the entire mechanism of disease which is complex and involves a variety of factors. This article suggests there is a causative link between Parkinsons and KGDHC deficiency, which speeds up neuro-degeneration.

"The activity of a key (and arguably rate-limiting) tricarboxylic acid cycle enzyme, the alpha-ketoglutarate dehydrogenase complex (KGDHC), was measured in the cerebellum of patients with PD. Activity in 19 PD brains was 50.5% of that in 18 controls matched for age, sex, post-mortem interval, and method of preservation"

Summary:: Female mice given alpha-ketoglutarate live longer, show fewer signs of aging.

Reduced caloric intake has been shown to prolong lives in test animals, but humans have found this difficult to maintain long term.
Other compounds have shown anti-aging effects but can have adverse effects on health:

It is thought that reduced caloric intake prolongs aging by increasing DNA maintenance and ROS protection. Abundant nutrients decrease lifespan by decreasing maintenance and promoting growth. There is evidence maintenance and growth are opposing forces in longevity.

This slide shows several actors that affect longevity. It is not mine, but the information is from a journal article which I am unable to find right now.

Lastly, this paints a simple picture of how restriction prolongs lifespan in mice.

 

[jim mcnamara]

@russ_watters - thanks for the correction. It always helps.