Arguing for Nicotinamide Riboside to Improve Hematopoietic Stem Cell Function

Researchers here argue for enhanced levels of NAD+ to boost stem cell function through improved mitochondrial function. This is an area of metabolism that has gained increasing attention of late, a second pass at the whole topic of sirtuins, mitochondrial function, and metabolism in aging. I'd say the jury is still out on whether it is worth pursing aggressively in human medicine. One or two early trials seem promising, in the sense of obtaining benefits that look similar to those derived from exercise, but the magnitude and reliability of those benefits is the important question.

The bone marrow stem cell population responsible for generating blood and immune cells, hematopoietic stem cells, declines in activity with age, as is the case for other stem cell populations. Some of this is due to intrinsic damage, but the evidence to date suggests that, up until very late life, the majority of the loss of activity can be overridden - it is an evolved response to rising levels of damage, possibly arising because it reduces cancer risk, rather than the direct consequence of damage. Thus researchers are in search of ways to safely override this response, via a variety of means.

Mitochondria are generally characterized as the powerhouse of the cell, since this is the site where energy is produced from ATP. In addition to energy production, mitochondria play a key role in several important cellular processes, including growth, signaling, differentiation, reactive oxygen species (ROS) production, apoptosis, and cell cycle control. Interestingly, unlike other cellular organelles, mitochondria have their own DNA, mitochondrial DNA (mtDNA), and several studies have indicated an association between the accumulation of mtDNA mutations and mammalian aging.

Historically, mitochondria have not been considered important in restoring the functions of aged hematopoietic stem cells (HSCs); however, emerging studies on rejuvenating HSCs suggest an association between sirtuins (SIRTs) and mitochondrial activities. In addition, a study on the deregulation of the mitochondrial stress-mediated metabolic system demonstrated that SIRT7 strongly influences the regenerative capacity of HSCs. Although the functions of musculoskeletal stem cells (MuSCs) and HSCs are distinct, alteration of the SIRT1-associated nuclear/mitochondrial axis appears to be a common hallmark of aging in both cell types.

Recent research suggests the possibility of restoring the mitochondrial functions of aged stem cells, including MuSCs, nerve tissue stem cells (NSCs), and melanocyte stem cells (McSCs), by NAD+ supplementation without genetic manipulation. The remedial effect of the NAD+ precursor nicotinamide riboside (NR) enhances mitochondrial functions in stem cells, including respiration, membrane potential, ATP production, and the mitochondrial unfolded protein response (UPR); however, these effects are not observed in stem cells with a SIRT1 deficit. Moreover, NR was found to suppress the process of senescence in adult NSCs and McSCs.

These findings have reinforced the notion that NAD+ precursors can function as a pharmacological tool to enhance SIRT activities. This, in turn, paves the way for clinical translation of NAD+ precursor treatment through further investigations of hematopoietic tissues. We review evidence relating mitochondrial dysfunction to HSC aging, and propose a strategy for mitochondrial-targeted recovery as a potentially safe, effective, and non-invasive method for the control or prevention of aging-related hematopoietic diseases.

Link: https://doi.org/10.3343/alm.2018.38.5.395

Comments

Most of the stem cell pools in the body are found in the bone marrow of the large bones of the legs. For this reason, I believe it is very important to maintain an active life of exercise with a focus on the leg bones and muscles. A sedentary person does not get enough movement of the legs to maintain the blood vessels and nutrient delivery to stem cell pools. As a result, the legs become frail and the stem cell pools degenerate, and fail to provide new cells needed through out the body. NAD+ helps by providing the energy to keep the immune system and other systems operating as we age.

Posted by: Biotechy Marcks at June 5th, 2018 9:23 AM

#Biotechy
I learned* recently that in adults hematopoiesis (and presumably active HSCs) is restricted to to the skull, sternum, ribs, vertebrae, and pelvis. Exercise is likely beneficial, in any case.
* https://www.youtube.com/watch?v=vaIyqbIZ2HE&t=3325s

Also news to me - physiological stem cell migration; it apparently happens every day and I had no idea. { What else is going on inside me that I don't know about?! }

Fucoidan is used to mobilize stem cells; it is found in edible brown algae such as kelp (kombu) and wakame. I don't know if dietary amounts will do anything beneficial with respect to stem cells, but I like seaweed so I eat it in moderation (too much iodine and heavy metal contamination are possible issues).

Posted by: CD at June 5th, 2018 10:41 AM

Disclaimer I take Nad+ precursors intermittently.

It seems that NR is one of the few spots that actually work. Hope strong an effect one can observe is an open question. I didn't witness anything measurable, unlike fasting and exercise. The effects might be measurable within older people, though.

I don't believe that we can get more than a couple of years of average life expectancy improvement. Nevertheless it is a low hanging fruit

Posted by: Cuberat at June 5th, 2018 11:42 AM

@CD: I have never heard of hematopoiesis and white blood cells not being produced in our long bone marrow throughout all or most of our lives as a normal process. If it is true that bone marrow in our long bones does deteriorate or degenerate in middle age or whenever, it should be studied to find out if it can be rejuvenated like the research going on for thymus gland rejuvenation. If we could rejuvenate the bone marrow production of red and white blood cells, it would be a major medical advance, since the long bones of the legs are such a large component of the total bone marrow of the human body.

Posted by: Biotechy Marcks at June 6th, 2018 12:34 PM

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