Can we fight cancer in ourselves with thoughts?

David Linden, a professor of neuroscience at Johns Hopkins Medical Schoo, has done an interesting piece on his own experience with a tumor in his heart, written 23 months after being told to expect to live 6 to 18 months after radiation and chemotherapy. The remnant tumor has become stable, and no metastases have developed.

And so, at the age of 61, I find myself in the weird and liminal state of having a terminal illness but feeling fine and having no immediate threat to my health...Since my diagnosis, I have received a lot of unsolicited medical advice. Much of this fell into the category of “mind/body medicine.”... meditate, breathe, pray or exercise in a certain way...when the explanations offered for the efficacy of mind/body medicine employ vague terms like “energy flow” and “resonance,” my baloney detector rings out strong and clear.

...part of my motivation to study neuroscience has been to understand the biological underpinnings of behavioral interventions in medicine. Some of the claims of mind/body medicine are almost certainly true, even if the pseudoscientific explanations offered for them are not...What about a potentially fatal illness that often manifests outside of the brain? Could the course of cancer progression be affected by behavioral practices like meditation or breath work?

...In recent years we have learned that certain types of cancer in the body receive nerve fibers, which originate in the brain and are passed to the body via electrochemical signals that travel in a chain from neuron to neuron. These include tumors of the lung, prostate, skin, breast and pancreas and the gastrointestinal system. This innervation of tumors often contributes to the growth and spread of cancer. In most cases, if you are a cancer patient and your tumor is innervated, then your prognosis is worse.

...the innervation of tumors and its role in cancer progression suggest an interesting hypothesis in mind/body medicine. If behavioral practices like meditation, exercise, breath work or even prayer can attenuate or reverse the progression of certain cancers (and, granted, that’s a huge if), then perhaps they do so, ultimately, by changing the electrical activity of the nerve cells that innervate tumors. It is a provocative idea and one that is testable in both humans and laboratory mice...if there is such a connection, it opens up the possibility that my own cognitive approach to terminal illness — in my case, hopefulness coupled with curiosity — could contribute to keeping my cancer at bay and do so, not through supernatural means, but by altering the electrical activity of tumor-innervating nerve fibers. I hope so, as however they are granted, these extra innings are a pure delight.

A new algorithm for predicting disease risk.

I pass on the text of this piece from Gina Kolata, and then the abstract of the article by Khera et al. she is referencing:

By surveying changes in DNA at 6.6 million places in the human genome, investigators at the Broad Institute and Harvard University were able to identify many more people at risk than do the usual genetic tests, which take into account very few genes.

Of 100 heart attack patients, for example, the standard methods will identify two who have a single genetic mutation that place them at increased risk. But the new tool will find 20 of them...The researchers are now building a website that will allow anyone to upload genetic data from a company like 23andMe or Ancestry.com. Users will receive risk scores for heart disease, breast cancer, Type 2 diabetes, chronic inflammatory bowel disease and atrial fibrillation...People will not be charged for their scores.

The abstract from Nature Genetics:

A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation. Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature, it has not yet been possible to use polygenic predictors to identify individuals at risk comparable to monogenic mutations. Here, we develop and validate genome-wide polygenic scores for five common diseases. The approach identifies 8.0, 6.1, 3.5, 3.2, and 1.5% of the population at greater than threefold increased risk for coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, and breast cancer, respectively. For coronary artery disease, this prevalence is 20-fold higher than the carrier frequency of rare monogenic mutations conferring comparable risk. We propose that it is time to contemplate the inclusion of polygenic risk prediction in clinical care, and discuss relevant issues.

Anti-aging molecule produced during fasting.

Diet trends like intermittent fasting and ketogenic diets are popular for their weight-loss effects. Han et al. now show that the β-hydroxybutyrate generated under these regimes slows aging of the vascular system, which is tied to overall body aging. It promotes vascular cell quiescence and inhibits cell senescence that accelerate aging. Here is the technical abstract:

Highlights

-β-hydroxybutyrate prevents the vascular cell senescence 

-β-hydroxybutyrate upregulates Oct4 expression via interacting with hnRNP A1 

-Oct4-mediated quiescence is able to attenuate hallmarks of senescenc 

-Circulating β-hydroxybutyrate alleviates the senescence of mouse aorta

Summary

β-hydroxybutyrate (β-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether β-HB alters the senescence pathway in vascular cells remains unknown. Here we report that β-HB promotes vascular cell quiescence, which significantly inhibits both stress-induced premature senescence and replicative senescence through p53-independent mechanisms. Further, we identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a direct binding target of β-HB. β-HB binding to hnRNP A1 markedly enhances hnRNP A1 binding with Octamer-binding transcriptional factor (Oct) 4 mRNA, which stabilizes Oct4 mRNA and Oct4 expression. Oct4 increases Lamin B1, a key factor against DNA damage-induced senescence. Finally, fasting and intraperitoneal injection of β-HB upregulate Oct4 and Lamin B1 in both vascular smooth muscle and endothelial cells in mice in vivo. We conclude that β-HB exerts anti-aging effects in vascular cells by upregulating an hnRNP A1-induced Oct4-mediated Lamin B1 pathway.

Graphical Abstract

Exercise and intermittent fasting improve brain plasticity and health

I have had numerous requests for a PDF of the article referenced in a Dec. 29, 2014 post - on how exercise and fasting stimulate brain plasticity and resilience - with the same title as this post.  It turns out that the reference pointed to by the link is open source. Readers should be able to download the article for themselves. Here is the text of the original post:

I thought it might be useful to point to this brief review by Praag et al. that references several recent pieces of work presented at a recent Soc. for Neuroscience Meeting symposium. The experiments indicate that exercise and intermittent energy restriction/fasting may optimize brain function and forestall metabolic and neurodegenerative diseases by enhancing neurogenesis, synaptic plasticity and neuronal stress robustness.  (Motivated readers can obtain the article from me.) Here is their central summary figure:

Exercise and IER/fasting exert complex integrated adaptive responses in the brain and peripheral tissues involved in energy metabolism. As described in the text, both exercise and IER enhance neuroplasticity and resistance of the brain to injury and disease. Some of the effects of exercise and IER on peripheral organs are mediated by the brain, including increased parasympathetic regulation of heart rate and increased insulin sensitivity of liver and muscle cells. In turn, peripheral tissues may respond to exercise and IER by producing factors that bolster neuronal bioenergetics and brain function. Examples include the following: mobilization of fatty acids in adipose cells and production of ketone bodies in the liver; production of muscle-derived neuroactive factors, such as irisin; and production of as yet unidentified neuroprotective “preconditioning factors.” Suppression of local inflammation in tissues throughout the body and the nervous system likely contributes to prevention and reversal of many different chronic disease processes.

Modest exercise gives maximum health benefits.

Gretchen Reynolds points to a study in the Mayo Clinic Proceedings that reviews studies published in PubMed since 2000 that included at least 500 runners and 5-year follow-up to analyze the relationship between running, cardiovascular disease, and all-cause mortality. The optimal dose of running required for protection is surprisingly small. Running for 20-30 minutes twice per week appears to give maximum benefits. Three to four times the duration of walking is needed to achieve the same benefits.