"Long before it's in the papers"
March 15, 2016


Study suggests why fasting diet may not work in humans

March 15, 2016
Courtesy of Leibniz Institute on Aging – 
Fritz Lipmann Institute
and World Science staff

Al­though stud­ies have shown that strict low-food di­ets may have a life-extending ef­fect, new re­search sug­gests there’s a se­ri­ous down­side: a pos­sibly fa­tal weak­en­ing of the im­mune sys­tem.

The find­ings sug­gest that this type of di­et, al­so known as ca­lor­ic re­stric­tion, may not help real-world peo­ple the same way it ben­e­fits some lab­o­r­a­to­ry an­i­mals.

Sci­en­tists from the Leib­niz In­sti­tute on Ag­ing–Fritz Lip­mann In­sti­tute in Je­na, Ger­ma­ny pub­lished the new find­ings in the Jour­nal of Ex­pe­ri­men­tal Med­i­cine on March 14.

Sev­er­al years ago, re­search­ers man­aged to pro­long the life­spans of ti­ny round­worms, fruit flies and rats by al­most 50 per­cent simply by mak­ing them eat less. This fu­eled hopes for find­ing a key to a long­er life for hu­mans too. But at­tempts to rep­li­cate the re­sults among apes and mon­keys led to mixed results, and en­thu­si­asms cooled some­what.

In the new work, ag­ing re­searcher Karl Lenhard Ru­dolph, sci­en­tif­ic di­rec­tor at the in­sti­tute, and col­leagues iden­ti­fied what looked like a trade­off. In ex­pe­ri­ments, stem cells or so-called “mas­ter” cells in the blood of di­eting mice were found to age slow­er—but the mouse im­mune sys­tems nearly shut down. Out­side of ster­ile lab con­di­tions, this could lead to deadly in­fec­tions, the re­search­ers ar­gued.

Stem cells are a type of un­dif­fer­en­ti­ated cell that can di­vide to be­come var­i­ous oth­er types of cells. Most cells in an adult or­gan­ism, by con­trast, are stuck be­ing the type of cell they al­ready are; their de­scen­dants will be the same.

The study fo­cused on stem cells in the blood that are re­spon­si­ble for build­ing ei­ther red blood cells or im­mune cells called lym­pho­cytes. Stem cells lose func­tion­al­ity or “age” eve­ry time they di­vide to cre­ate new cells. To avoid this, they rest most of the time and are only ac­ti­vat­ed when a mas­sive cell re­pro­duc­tion is needed, such as af­ter a big loss of blood. 

In the stu­dy, the re­search­ers in­ves­t­i­gated the ef­fects of food re­stric­tion by 30 per­cent, a per­centage si­m­i­lar to that used in many past stud­ies. A chief find­ing was that the stem cells con­tin­ued to rest even if sim­u­lat­ed stress would have re­quired their ac­tiva­t­ion, so they did­n’t “age” at all. On the oth­er hand, pro­duc­tion of lym­pho­cytes—needed for im­mune de­fense—plunged by up to 75 per­cent, leav­ing mice more vul­ner­a­ble to bac­te­ri­al in­fec­tions. 

“The study pro­vides the first ex­pe­ri­men­tal ev­i­dence that long-term ca­lor­ic re­stric­tion—as in­ter­ven­tion to slow down ag­ing—increases stem cell func­tion­al­ity, but re­sults in im­mune de­fects in the con­text of pro­longed bac­te­ri­al in­fec­tion, too. Thus, pos­i­tive ef­fects of a di­et are not trans­fer­a­ble to hu­mans one-to-one,” Ru­dolph said. 

Some­what con­sist­ent with the new find­ings, it’s well known that heav­i­er pa­tients tend to sur­vive more of­ten than lean pa­tients when deal­ing with sep­sis, a type of se­vere com­plica­t­ion from an in­fec­tion, added Mi­chael Bau­er, di­rec­tor of the Cen­ter for Sep­sis Con­trol and Care at Un­ivers­ity Hos­pi­tal Je­na.

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Although studies have shown that strict low-food diets may have a life-extending effect, new research suggests there’s a serious downside: a possibly fatal weakening of the immune system. The findings suggest that this type of diet, also known as caloric restriction, may not help real-world people the same way it benefits some laboratory animals. Scientists from the Leibniz Institute on Aging–Fritz Lipmann Institute in Jena, Germany published the new findings in the Journal of Experimental Medicine on March 14. Several years ago, researchers managed to prolong the lifespans of tiny roundworms, fruit flies and rats by almost 50% simply by making them eat less. This fueled hopes for finding a key to a longer life for humans too. But attempts to replicate the results among apes weren’t as successful, and enthusiasms cooled somewhat. In the new work, aging researcher Karl Lenhard Rudolph, scientific director at the institute, and colleagues identified what looked like a tradeoff. In experiments, stem cells or so-called “master” cells in the blood of dieting mice were found to age slower—but the mouse immune systems nearly shut down. Outside of sterile lab conditions, this could lead to deadly infections, the researchers argued. Stem cells are a type of undifferentiated cell that can divide to become various other types of cells. Most cells in an adult organism, by contrast, are stuck being the type of cell they already are; their descendants will be the same. The study focused on stem cells in the blood that are responsible for building either red blood cells or immune cells called lymphocytes. Stem cells lose functionality or “age” every time they divide to create new cells, and therefore, they rest most of the time and are only activated when a massive cell reproduction is needed, such as after a big loss of blood. In the study, the researchers investigated the effects of food restriction by 30 percent, a percentage similar to that used in many past studies. A chief finding was that the stem cells continued to rest even if simulated stress would have required their activation, so they didn’t “age” at all. On the other hand, production of lymphocytes—needed for immune defense—plunged by up to 75%, leaving mice more vulnerable to bacterial infections. “The study provides the first experimental evidence that long-term caloric restriction—as intervention to slow down aging—increases stem cell functionality, but results in immune defects in the context of prolonged bacterial infection, too. Thus, positive effects of a diet are not transferable to humans one-to-one,” Rudolph said. Somewhat consistent with the new findings, it’s well known that heavier patients tend to survive more often than lean patients when dealing with sepsis, a type of severe complication from an infection, added Michael Bauer, director of the Center for Sepsis Control and Care at University Hospital Jena.