Fight Aging!

Regular intermittent fasting practices such as alternate day fasting are not as well studied as calorie restriction, but do seem to have similar effects with regard to improved health and extended healthy life spans. In some studies this is absolutely because intermittent fasting is reducing overall calorie intake. But even in studies where the calorie intake is controlled, so that fasting individuals consume the same amount as non-fasting controls, lesser benefits to health and longevity in rodents are still observed. So as is usually the case in the life sciences the underlying biology must be a complex mess of overlapping mechanisms.

We're probably going to be hearing a lot more about these overlapping mechanisms of intermittent fasting in the next few years as at least one group is working towards clinical trials based on human studies, and the folk involved have in mind starting up a company to market some sort of related products based on their data.

The latest work from the group looks at the details of the relationship between fasting and immune function, which turns out to be of interest to the cancer research community, among others. Ways to better recover from treatments like chemotherapy that greatly impact the immune system by thinning the ranks of white blood cells are high on the priority list. Since there is already a fair amount of work underway on generating better outcomes for cancer patients by combining calorie restriction with chemotherapy, it shouldn't be surprising to find that there is funding for work on intermittent fasting as well.

Fasting triggers stem cell regeneration of damaged, old immune system

Cycles of prolonged fasting not only protect against immune system damage - a major side effect of chemotherapy - but also induce immune system regeneration, shifting stem cells from a dormant state to a state of self-renewal. In both mice and a Phase 1 human clinical trial, long periods of not eating significantly lowered white blood cell counts. In mice, fasting cycles then "flipped a regenerative switch": changing the signaling pathways for hematopoietic stem cells, which are responsible for the generation of blood and immune systems, the research showed.

The study has major implications for healthier aging, in which immune system decline contributes to increased susceptibility to disease as we age. By outlining how prolonged fasting cycles - periods of no food for two to four days at a time over the course of six months - kill older and damaged immune cells and generate new ones, the research also has implications for chemotherapy tolerance and for those with a wide range of immune system deficiencies, including autoimmunity disorders.

Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression

Because during prolonged fasting (PF) mammalian organisms minimize energy expenditure in part by rapidly reducing the size of a wide range of tissues, organs, and cellular populations including blood cells, the reversal of this effect during refeeding represents one of the most potent strategies to regenerate the hematopoietic and possibly other systems and organs in a coordinated manner.

Here, we show that PF causes a major reduction in white blood cell (WBC) number, followed, during refeeding, by a coordinated process able to regenerate this immune system deficiency by changes beginning during the fasting period, which include a major increase in [stem cell activity and lineage balancing]. In fact, we show that PF alone causes a 28% decrease WBC number, which is fully reversed after refeeding. Even after WBCs are severely suppressed or damaged as a consequence of chemotherapy or aging, cycles of PF are able to restore the normal WBC number and lineage balance, suggesting that the organism may be able to exploit its ability to regenerate the hematopoietic system after periods of starvation, independently of the cause of the deficiency.

To begin to determine whether PF cycles can potentially promote a similar effect in humans, we also analyzed the hematological profiles of cancer patients from a phase I clinical trial for the feasibility and safety of a 24 - 72 hr PF period in combination with chemotherapy. Although three different platinum-based drug combinations were used, the results from a phase I clinical trial indicate that 72 but not 24 hr of PF in combination with chemotherapy were associated with normal lymphocyte counts and maintenance of a normal lineage balance in WBCs. These encouraging preliminary results will need to be expanded and confirmed in the ongoing phase II randomized phase of the clinical trial.

As modern research results go, this ranks highly if scored in terms of cost and difficulty to implement for any given individual (near zero) versus benefits derived (greater than zero). That is true of anything relating to calorie restriction or fasting, however. Anyone can do it, though in this case the cautious late adopter would wait a few years for more human data that uses relatively healthy old people rather than cancer patients undergoing chemotherapy as a baseline. It may well be that this doesn't in fact do much for the aged immune system in people, while still being a helpful enough approach to use in conjunction with cancer treatments. Trying this in old people would be a comparatively low cost study to set up, so I imagine we won't have to wait too long for that data to emerge.