Navigation Links
Scientists find molecular trigger that helps prevent aging and disease
Date:11/18/2009

Researchers at Mount Sinai School of Medicine set out to address a question that has been challenging scientists for years: How do dietary restrictionand the reverse, overconsumptionproduce protective effects against aging and disease?

An answer lies in a two-part study led by Charles Mobbs, PhD, Professor of Neuroscience and of Geriatrics and Palliative Medicine at Mount Sinai School of Medicine, published in the November 17 edition of the journal Public Library of Science Biology. The study, titled "Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling," examines how dietary restriction and a high-caloric diet influence biochemical responses.

Dr. Mobbs and his colleagues unraveled a molecular puzzle to determine that within certain parameters, a lower-calorie diet slows the development of some age-related conditions such as Alzheimer's disease, as well as the aging process. How the diet is restrictedwhether fats, proteins or carbohydrates are cutdoes not appear to matter. "It may not be about counting calories or cutting out specific nutrients," said Dr. Mobbs, "but how a reduction in dietary intake impacts the glucose metabolism, which contributes to oxidative stress." Meanwhile, a high calorie diet may accelerate age-related disease by promoting oxidative stress.

Dietary restriction induces a transcription factor called CREB-binding protein (CBP), which controls the activity of genes that regulate cellular function. By developing drugs that mimic the protective effects of CBP those usually caused by dietary restriction scientists may be able to extend lifespan and reduce vulnerability to age-related illnesses.

"We discovered that CBP predicts lifespan and accounts for 80 percent of lifespan variation in mammals," said Dr. Mobbs. "Finding the right balance is key; only a 10 percent restriction will produce a small increase in lifespan, whereas an 80 percent restriction will lead to a shorter life due to starvation."

The team found an optimal dietary restriction, estimated to be equivalent to a 30 percent caloric reduction in mammals, increased lifespan over 50 percent while slowing the development of an age-related pathology similar to Alzheimer's disease.

The first part of the study looked at C. elegans, a species of roundworm, that were genetically altered to develop Alzheimer's disease-like symptoms. Dr. Mobbs and his team reduced the roundworms' dietary intake by diluting the bacteria the worms consume. In these types of roundworms, human beta amyloid peptide, which contributes to plaque buildup in Alzheimer's disease, is expressed in muscle, which becomes paralyzed as age progresses. This model allowed researchers to readily measure how lifespan and disease burden were simultaneously improved through dietary restriction.

The researchers found that when dietary restriction was maintained throughout the worms' adulthood, lifespan increased by 65 percent and the Alzheimer's disease-related paralysis decreased by about 50 percent.

"We showed that dietary restriction activates CBP in a roundworm model, and when we blocked this activation, we blocked all the protective effects of dietary restriction," said Dr. Mobbs. "It was the result of blocking CBP activation, which inhibited all the protective effects of dietary restriction, that confirmed to us that CBP plays a key role in mediating the protective effects of dietary restriction on lifespan and age-related disease. "

In the second part of study, Dr. Mobbs and his team looked at the other end of this process: What happens to CBP in a high-calorie diet that has led to diabetes, a disease in which glucose metabolism is impaired? Researchers examined mice and found that diabetes reduces activation of CBP, leading Dr. Mobbs to conclude that a high-calorie diet that leads to diabetes would have the opposite effect of dietary restriction and would accelerate aging.

Dr. Mobbs hypothesizes that dietary restriction induces CBP by blocking glucose metabolism, which produces oxidative stress, a cellular process that leads to tissue damage and also promotes cancer cell growth. Interestingly, dietary restriction triggers CBP for as long as the restriction is maintained, suggesting that the protective effects may wear off if higher dietary intake resumes. CBP responds to changes in glucose within hours, indicating genetic communications respond quickly to fluctuations in dietary intake.

"Our next step is to understand the exact interactions of CBP with other transcription factors that mediate its protective effects with age," said Dr. Mobbs. "If we can map out these interactions, we could then begin to produce more targeted drugs that mimic the protective effects of CBP."


'/>"/>

Contact: Mount Sinai Press Office
newsnow@mountsinai.org
212-241-9200
The Mount Sinai Hospital / Mount Sinai School of Medicine
Source:Eurekalert

Related medicine news :

1. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
2. Scientists Probe Sepsis Deadly Secrets
3. Scientists puzzled by severe allergic reaction to cancer drug in the middle Southern US
4. Scientists Develop Natural Protection for Stored Foods
5. Scientists detect presence of marburg virus in african fruit bats
6. Scientists Spot Brains Free Will Center
7. Scientists ID Likely Culprit in Popcorn Lung
8. Scientists explain how insulin secreting cells maintain their glucose sensitivity
9. Scripps Research scientists shed new light on how antibodies fight HIV
10. Scientists, physicians present latest findings in personalized cancer treatment and prevention
11. Scientists demonstate link between genetic variant and effectiveness of smoking cessation meds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 26, 2016 , ... Brent Kasmer, a legally blind and certified personal trainer is helping ... fitness app. The fitness app plans to fix the two major problems leading the fitness ... size fits all type program , They don’t eliminate all the reasons people ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... "With 30 ... their specific project," said Christina Austin - CEO of Pixel Film Studios. , ... and all within Final Cut Pro X . Simply select a ProHand generator ...
(Date:6/25/2016)... ... ... Conventional wisdom preaches the benefits of moderation, whether it’s a matter of indulgence ... high can result in disappointment, perhaps even self-loathing. However, those who set the bar ... from PsychTests.com reveals that behind the tendency to set low expectations is ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... Conference and Scientific Sessions in Dallas that it will receive two significant new ... the grants came as PHA marked its 25th anniversary by recognizing patients, medical ...
(Date:6/24/2016)... ... , ... People across the U.S. are sharpening their pencils and honing their ... in which patients and their families pay tribute to a genetic counselor by nominating ... of Genetic Counselors (NSGC) Annual Education Conference (AEC) this September. , In April, ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... INDIANAPOLIS , June 23, 2016 Roche ... received 510(k) clearance for its Elecsys BRAHMS PCT (procalcitonin) ... severe sepsis or septic shock. With this clearance, Roche ... provide a fully integrated solution for sepsis risk assessment ... associated with bacterial infection and PCT levels in blood ...
(Date:6/23/2016)... VIEW, Calif. , June 23, 2016 ... a.m. CST on Thursday, July 7, 2016 , , , ... kayla.belcher@frost.com ) , , , , EXPERT PANELISTS:  , ... Nitin Naik; Senior Industry Analyst, Christi Bird; Senior Industry Analyst, Divyaa ... The global pharmaceutical industry is witnessing an ...
(Date:6/23/2016)... 23, 2016 The vast majority of dialysis ... facility.  Treatments are usually 3 times a week, with ... including travel time, equipment preparation and wait time.  This ... grueling for patients who are elderly and frail.  Many ... and rehabilitation centers for some duration of time. ...
Breaking Medicine Technology: