Joslin researchers show that caloric restriction lowers levels of innate immunity and inflammation, leading to increased longevity.
Scientists have known for decades that caloric restriction leads to a longer lifespan. It has also been observed that chronic inflammation increases with age. But any relationship between the two had remained unexplored.
But in a new study, published today in Cell Metabolism, researchers at Joslin Diabetes Center have uncovered a new mechanism of lifespan extension that links caloric restriction with immune system regulation.
“Modulating immune activity is an important aspect of dietary restriction,” says Keith Blackwell, MD, PhD, Associate Research Director and Senior Investigator at Joslin, and Professor of Genetics at Harvard Medical School, senior author on the paper. “And it is important for longevity regulation and, in this context, increasing lifespan.”
In this study, Dr. Blackwell and his team found that caloric restriction reduces levels of innate immunity by decreasing the activity of a regulatory protein called p38, triggering a chain reaction effect ending in a reduced immune response.
Innate immunity is like the security guard of the body, keeping an eye out for any unwelcome bacteria or viruses. If the innate immune system spots something, it activates an acute immune response. We need some degree of both kinds of immunity to stay healthy, but an overactive innate immune system—which occurs more often as we age—means constant low-grade inflammation, which can lead to myriad health issues.
“[Before this study,] people looked what happens to immunity to aging in humans, but no one had ever looked in any organism at whether modulating immunity or its activities is involved in lifespan extension or can be beneficial as part of an anti-aging program,” says Dr. Blackwell.
The research was conducted in the microscopic nematode worm C. elegans. The most fundamental genes and regulatory mechanisms found in these worms are typically simpler versions of those present in humans, making them a good model for studying human aging, genetics, and disease.
Dr. Blackwell and his team analyzed the levels of proteins and actions of genetic pathways during periods of caloric restriction. They were able to zero in on a particular genetic pathway that was regulated by the p38 protein. They saw that when p38 was totally inactive, caloric restriction failed and had no impact on innate immunity. When it was active, but at lower levels than normal, it triggered the genetic pathways that turned down the innate immune response to an optimal level.
“That was the most surprising thing we found. The pathway was down regulated even though it was critical,” says Dr. Blackwell.
That this immune-regulating response was activated by nutrients, rather than bacteria, was also surprising. This adds to a growing body of evidence tying metabolism to the immune system.
“This is really an emerging field in mammals now, so called immunometabolism—the idea that there are ancient links between metabolism and immunity,” says Dr. Blackwell. “We were able to show in this really very primitive immune system that it is regulated metabolically, and affects lifespan and health independently of an anti-pathogen function. That is when I started calling this a primitive immunometabolic pathway or an immunometabolic regulation.”
After making this discovery, Dr. Blackwell was curious to know if the well-known longevity mechanism of reduced IGF1 signaling also acted on the immune system. For over 20 years, study after study in many different organisms have confirmed that lower levels of IGF1 signaling contributes to a longer lifespan. This is thought to be due to the activation of protective factors by a protein called FOXO (called DAF-16 in C. elegans).
In this new study, Dr. Blackwell and his team discovered that when IGF signaling was reduced in the worms, the chain reaction set off by the FOXO-like DAF-16 not only boosted protective mechanisms, but also led to a reduction of the worms’ appetites. This naturally put the subjects in a state of caloric restriction.
“This links the growth mechanism [of IGF1 signaling] to food consumption and food seeking behavior in a big way,” says Dr. Blackwell.
A reduction in the activity of the FOXO-like gene seems to tell the worms that they are in a fasting-like state, and that nutrients may be scarce. This directs the worms to conserve energy, leading to a reduction in food intake. This self-imposed caloric restriction then leads to the lowering of the innate immune response. Dr. Blackwell plans to further study how the FOXO protein acts to suppress appetite, and to understand whether that might eventually lead to drug development.
The genes responsible for the phenomena observed in this study are conserved in humans. This opens up the possibility of human medical applications, from optimizing the immune system to drug development for appetite control.
“The ultimate goal is to be able to manipulate healthy lifespan in a person,” says Dr. Blackwell. “Not to make people live to 120, 130, but to extend the period of healthy life. And chronic inflammation is a major factor in human aging. The hope is that some of the specific mechanisms could translate to optimizing immune function in humans during aging to enhance health in human lifespan.”
The Latest on: Longevity
via Google News
The Latest on: Longevity
- Microbial ageing and longevityon September 18, 2019 at 6:24 am
Longevity reflects the ability to maintain homeostatic conditions necessary for life as an organism ages. A long-lived organism must contend not only with environmental hazards but also with internal ...
- The Alzheimer's Research and Prevention Foundation Brain Longevity® Therapy Training & Symposium Approved for Extensive CEUson September 18, 2019 at 3:07 am
TUCSON, Ariz., Sept. 18, 2019 /PRNewswire/ -- The Alzheimer's Research and Prevention Foundation's (ARPF) Brain Longevity Therapy Training and Symposium has been approved for extensive CEU hours ...
- Biden touts political longevity in bid for union support at Philly event: ‘You all know me’on September 17, 2019 at 7:18 pm
PHILADELPHIA — Former Vice President Joe Biden leaned hard into his long history of support for and from organized labor Tuesday, telling hundreds of union members in Philadelphia he has never let ...
- Dynamical controls on the longevity of a non-linear vortex : The case of the Lofoten Basin Eddyon September 17, 2019 at 2:32 pm
The Lofoten Basin is the largest oceanic reservoir of heat in the Nordic Seas, and the site of important heat fluxes to the atmosphere. An intense permanent anticyclone in the basin impacts the ...
- Did Longevity Spoil Eli Manning’s Overall Body of Work?on September 17, 2019 at 8:23 am
The New York Giants named rookie Daniel Jones as the starting quarterback ahead of their week three matchup with the Tampa Bay Buccaneers. Giants’ fans went from questioning Jones’ draft selection to ...
- Striving for longevity? You’ll need the right insurance coverage in placeon September 17, 2019 at 7:31 am
For more information about these three types of insurance or other insurance plans, call Debbie Aragon at 970-879-1756, or visit www.debbiearagon.com. Humans are unlocking the secrets to longevity, ...
- 104-Year-Old Woman's Secret to Longevity: 'Keep Your Mind Busy'on September 13, 2019 at 12:27 pm
A 104-year-old woman in Corsicana who still dances and plays the piano says her secret to good health is to keep her mind active. Anna Bell Swanner was born in Cone, Texas, on Feb. 28, 1915. Cone is ...
- Britain’s oldest identical twins, 95, share their secrets to longevityon September 12, 2019 at 9:15 pm
At 95 years of age, Britain’s oldest identical twins chalk up their longevity to abstinence, raw sausage and plenty of Guinness. “Just a link of sausage and spread it on your bread,” Lilian ...
- 95-year-old twins credit Guinness, 'no sex' to longevityon September 12, 2019 at 5:11 pm
LONDON (Fox News) - Apparently abstinence and alcohol are the key to a long life. Identical twin sisters Lilian “Lil” Cox and Doris Hobday are Britain’s oldest twins, having turned 95 on July 20. The ...
- Project Longevity seeks Hartford manager to aid in reducing gang violenceon September 12, 2019 at 11:21 am
NEW HAVEN — Project Longevity is seeking a manager to head the organization’s efforts to reduce violence in Hartford. According to a job description posted by the organization, the Project Manger ...
via Bing News