Restoring blood component regeneration process could be just like changing the oil in a car.

A research team at the University of Colorado Anschutz Medical Campus and School of Medicine has found a way to promote red blood cell production, which could prevent disease and prolong healthspan. Former US President Donald Trump got into trouble when he started riffing about injecting people with disinfectants at a press conference; now a little bit of acid in the diet turns out to have regenerative properties.

Longevity.Technology: Approximately 70% of human cells are red blood cells, so that’s 20–30 trillion red blood cells pumping around your body at any given time. However, they are short-lived, lasting for only 120 days, and this means the body is continuously generating them, 200 billion or so every single day. Red blood cell production declines with age, and this can lead to a variety of health problems, from anaemia to blood cancers. Being able to maintain quality and quantity of red blood cells would boost vitality, as more oxygen would be getting to muscles and organs, and also prevent certain diseases.

The continual red blood cell production is due to the capacity of hematopoietic stem cells (HSCs) to multiply and differentiate into all the blood cell types; this mechanism can become impaired as we age.

Likening the concept to changing the oil in a car, Angelo D’Alessandro, PhD, study co-author, said: “If we manage to keep 90% of the cells in our body young, chances are that much of our body is going to be young.”

Breakdown of cellular proteins is an important step in regulating them and controlling their quality; this protein degradation also allows for critical amino acids to be recycled.

Chaperone-mediated autophagy (CMA) targets specific proteins for degradation, using chaperone proteins to directly guide proteins to the lumen of the lysosome, an organelle packed with digestive enzymes that can break down cell parts, molecules, bacteria or viruses.

The Colorado research team focused on chaperone-mediated autophagy (CMA), a mechanism they determined responsible for the degradation of red blood cells. Like a housekeeper on a go-slow, as we age the CMA process can fail to clear damaged proteins and other waste products, hampering the HSCs’ capacity to make new, healthy red blood cells.

Targeting one key protein (LAMP2A), which regulates chaperone-mediated autophagy and whose expression and activity declines with age, the researchers used genetic, dietary and pharmacological interventions to restore young haematopoiesis (formation of blood cellular components) in a cohort of old laboratory mice.

“… we could make old mice look more like young mice in the capacity to generate new blood cells.”

The research team demonstrated that metabolic enzyme (FADS2), which is involved in fatty acid metabolism, loses function with age, leading to a reduction in healthy blood cell formation. The scientists introduced gamma linolenic acid (GLA), a product of the failing enzyme, into the rodents’ diets, and found that cell regeneration was improved as a result [1]. GLA can be found in vegetable oils such as evening primrose oil, blackcurrant seed oil, borage seed oil and hemp seed oil, as well as in hemp seeds, oats, barley and spirulina in smaller amounts. This means that there could the possibility of dietary solutions to combat falling GLA levels in the future.

“We showed that a failure in the CMA system results in alterations of lipid metabolism by lack of degradation of age-damaged FADS2 in the stem cells,” said D’Alessandro. “By switching mice to a diet rich in GLA, we could fix the phenotype. That is, we could make old mice look more like young mice in the capacity to generate new blood cells [2].”

Because the CMA dysfunctions in mice mirror those in older humans (aged 70 and above), the researchers hope their discovery could pave the way to reversing the aging process of HSCs in people, setting the stage for a number of medical interventions and therapies.

Failing CMA can lead to a build-up of waste products and this has previously been linked to neurological degenerative diseases, such as Alzheimer’s and Parkinson’s; D’Alessandro commented that his past research demonstrated that chronic inflammation results in alteration of the blood-regenerating process, meaning that this discovery could translate to improved healthspan that lasts well into old age [2].

“While our results may not help people live forever, they may contribute to a healthier life as we get old,” he said. “While extending the lifespan might still be out of reach, I think that improving our health span is an actionable goal in the next 10 or 15 years [2].”

Julie Reisz Haines, PhD, study co-author, commented: “The most exciting part of this work is that by leveraging complimentary data from these very advanced techniques (metabolomics, proteomics, and very elegant in vivo studies), it is possible to begin uncovering a biological mechanism at the molecular level for understanding how HSCs age and the links between aging and stemness [2].

[1] https://www.nature.com/articles/s41586-020-03129-z#Sec10
[2] https://news.cuanschutz.edu/news-stories/scientists-discover-ways-of-making-old-blood-new-again

Image credit: Arek Socha / Pixabay and Phil Silverman / Shutterstock