Calorie Restriction Slows Neural Stem Cell Decline, Perhaps via Reduced Cellular Senescence and Inflammation

The practice of calorie restriction is shown to slow all aspects of aging, though its effects on life span are much smaller in humans than in short-lived species. The health effects in our species are worth the effort, however, given that calorie restriction is both reliable in its production of benefits and free. Here, researchers note that calorie restriction slows the consequences of aging in neural stem cell populations, as is the case for stem cell populations elsewhere in the body as well. They suggest that this is the downstream consequence of reduced levels of cellular senescence and chronic inflammation.

Neural stem cells support the brain via neurogenesis, the creation of new neurons that can take their place in brain tissue and contribute to function. Neurogenesis diminishes with age, in line with the fact that stem cell populations throughout the body decline in activity with the progression of degenerative aging. One explanation for this phenomenon is that it is part of an evolved balance between cancer risk and the slow decline of tissue failure. Too much stem cell activity in a damaged system will raise the risk of cancer. The widespread use of stem cell therapies so far suggests that if this is the case, it isn't a finely-tuned balance; there is a lot of room to increase stem cell activity without provoking large increases in cancer risk.

The adult brain can generate new neurons from neural stem cells. The process of neurogenesis occurs throughout life primarily in the dentate gyrus of the hippocampus and the subventricular zone (SVZ). This process is highly regulated, and although the signals that control neurogenesis are not yet fully understood, it is known that neurogenesis declines with age, suggesting that the neurogenic signals are susceptible to age-related deficits observed elsewhere in the brain.

Calorie restriction is one mechanism by which age-related deficits may be reduced in aged animals. Calorie restriction can markedly increase mean and maximum lifespan and improve physiologic markers of health, including insulin sensitivity, body mass index, and plasma markers of cardiovascular disease. Calorie restriction has beneficial effects in blood and muscle stem cell function, and can protect against neuronal damage in neurodegenerative models. In the hippocampus, calorie restriction enhances proliferation of progenitor cells, although whether these newly born cells survive and mature into neurons is not clear.

Chronic inflammation is a known factor in aging, suggesting that inflammatory cells likely contribute to the development of deficits in the aging brain. Cellular senescence is a phenomenon by which cellular division ceases in the aged organism, and is modifiable in laboratory models. Inflammation is associated with senescence in in vitro models because senescent cells secrete pro-inflammatory cytokines.

In this study, we show that calorie restriction is protective against age-related increases in senescence and microglia activation and pro-inflammatory cytokine expression in an animal model of aging. Further, these protective effects mitigated age-related decline in neuroblast and neuronal production, and enhanced olfactory memory performance, a behavioral index of neurogenesis in the SVZ. Our results support the concept that calorie restriction might be an effective anti-aging intervention in the context of healthy brain aging.

Link: https://doi.org/10.18632/aging.101731

Comments

CR could slow a lot of decline just virtue of slowing the metabolism. It for sure "messes" with the metabolism to reduce the damage created. And we have a good indication that it also up-regulates apoptosis and damage repair mechanisms.

>Neurogenesis diminishes with age, in line with the fact that stem cell populations throughout the body decline in activity with the progression of degenerative aging. One explanation for this phenomenon is that it is part of an evolved balance between cancer risk and the slow decline of tissue failure.

Posted by: cuberat at January 21st, 2019 1:28 PM

I wish those companies working on filtering cerebral fluid as an approach to longevity would look for makers in the fluid of brain cell death. I worry that during my monthly 4 day fasts that my brain isn't getting enough calories to keep all the cells alive. There is some compelling evidence that statins can lead to neuro-degeneration, and it may be due to a lack of or removal of cholesterol. Wouldn't it be a good idea to do a characterization of spinal fluid under various calorie intakes and diet?

Re: Stem cells. I'm operating under the assumption that resistance training with enough weight to slightly bend your bones (with fewer reps) actually forces fluids from the marrow out through a few holes in them, bringing with it some stem cells. The bigger bones have more marrow and bigger holes. So, I do leg extensions and curls, despite concerns that there is stress on the knees. I wish there was a way to confirm this, and I worry that I'm burning up a limited pool of stem cells in the marrow.

Posted by: Tom Schaefer at January 22nd, 2019 8:16 AM

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