This Is MS Multiple Sclerosis Knowledge & Support Community

brm wrote:I was wondering if anyone has experience with some kind of fasting, like alternate day fasting, 5:2 fasting, or even longer fasts. For instance, how many hours at a time did you refrain from eating? And of course, did you notice any effects (positive or negative) on your MS?

In principle it should have a beneficial influence on your health, but whether this is so for pwMS I do not know... But it has me interested.

brm wrote:I saw his horizon documentary called "Eat, fast and live longer". Very interesting stuff, it was that show that got me interested in all this.

Thanks,
brm

New England Journal of Medicine
Source URL: http://www.nejm.org/doi/full/10.1056/NEJMc1303158

Autophagy in Human Health and Disease
N Engl J Med 2013; 368:1845-1846
May 9, 2013DOI: 10.1056/NEJMc1303158


Choi et al. (Feb. 14 issue)1 describe autophagy activation in several human diseases. However, a worthy point was missed, since autophagic function in autoimmune diseases was not considered. A growing body of evidence provides support for the involvement of autophagy in immunity and autoimmunity.2,3 Indeed, autophagy is known to have a role in thymic selection of T cells, survival of B cells, immune tolerance, and antigen presentation.2 It enables intracellular self-antigens to enter major-histocompatibility-complex class II pockets, which are subsequently recognized by activated T cells. Accordingly, autophagic dysfunction may promote the development of systemic autoimmune diseases such as lupus,4 and a failure in autophagy may play a role in autoinflammatory and autoimmune diseases such as the tumor necrosis factor receptor–associated periodic syndrome and Crohn's disease.3,5 Moreover, several allelic variants of autophagy-related genes have been linked to autoimmunity4 and autoinflammation.2

Data are lacking to clarify these issues; however, the autophagic process is probably involved in the establishment and maintenance of immune tolerance and the proper effectiveness of the immune system.

Andrea Doria, M.D.
Mariele Gatto, M.D.
Leonardo Punzi, M.D.
University of Padua, Padua, Italy

We strongly agree with Doria et al. about the prospect that autophagy may contribute to the pathogenesis of autoimmune disorders. Autophagy can exert profound effects on inflammation and the regulation of innate and adaptive immunity. Indeed, autophagy can regulate core inflammatory responses (e.g., interferon production, inflammasome activation, and cytokine maturation) and contribute to efferocytosis (removal of dead or dying cells), antigen presentation, B-cell survival, regulation of antibody production, and T-cell maturation1; these processes could affect immune tolerance and the progression of autoimmune disease.

In our article, we mention that single-nucleotide polymorphisms (SNPs) of ATG5, an autophagy-related gene (ATG), are associated with systemic lupus erythematosus, an autoimmune disease, and that SNPs in ATG16L1, nucleotide-binding oligomerization domain–containing protein 2 (NOD2), and immunity-related p47 guanosine triphosphatase M protein (IRGM) genes are associated with Crohn's disease, an autoinflammatory condition. However, the effect of these SNPs on autophagy remains unclear. We add that autoimmunity develops in mice that are deficient in thymic Atg5.1 Furthermore, human and murine lupus T cells have impaired autophagy and increased activation of the mammalian (or mechanistic) target of rapamycin.2 The link between autophagy and autoimmunity remains incompletely understood, but it warrants extensive investigation for therapeutic development. We regret that we could not cite all relevant literature.

Augustine M.K. Choi, M.D.
Stefan W. Ryter, Ph.D.
Brigham and Women's Hospital, Boston, MA
amchoi@rics.bwh.harvard.edu

Beth Levine, M.D.
University of Texas Southwestern Medical Center, Dallas, TX