Navigation Links
Aging gracefully requires taking out the trash

La Jolla, CA Suppressing a cellular cleanup-mechanism known as autophagy can accelerate the accumulation of protein aggregates that leads to neural degeneration. In an upcoming issue of Autophagy, scientists at the Salk Institute for Biological Studies report for the first time that the opposite is true as well: Boosting autophagy in the nervous system of fruit flies prevented the age-dependent accumulation of cellular damage in neurons and promoted longevity.

We discovered that levels of several key pathway members are reduced in Drosophila neural tissue as a normal part of aging, says senior author Kim Finley, Ph.D., a scientist in the Cellular Neurobiology Laboratory, which suggests there is an age-dependent suppression of autophagy that may be a contributing factor for human neurodegenerative disorders like Alzheimers disease.

As the American population grows older, questions regarding the aging process and how it can be positively influenced are increasingly becoming the focus of scientific research and public interest. The age-related accumulation of proteins and lipids damaged by chemically aggressive forms of oxygen is considered by most in the geriatrics field to be a normal part of the aging process. As a result in most age-associated diseases, such as Alzheimers, damaged proteins accumulate in excessive amounts, which leads to progressive cell death in the brain.

All cells undergo autophagy literally self-eating, which requires the assembly of specialized vesicles called autophagosomes. These vesicles surround or engulf damaged cellular proteins or structures and then traffic the bagged garbage to a second group of vesicles, which disposes of the trash with the help of digestive enzymes. This process can be enhanced when animals are placed on a calorie-restricted diet, a regime known to extend lifespan.

The activation of autophagy facilitates the removal of damaged molecules that accumulate during cellular aging, says Finley. This may be particularly important in the nervous system since neurons produce damaged molecules at a much higher rate than most cell types. Keeping cells free of damaged molecules is critical for neurons because unlike many cells, they do not divide or replace themselves once created at birth. They rely on autophagy together with other clearance and detoxification pathways to keep themselves healthy and functioning for decades, explains Finley.

For their studies, the Salk researchers turned to the fruit fly Drosophila, a powerful model organism, whose genetics can easily be manipulated. When initial experiments indicated that the expression of several autophagy genes decreased over the normal lifespan of fruit flies, the Salk researchers focused on one particular protein, Atg8a. This protein is an essential component needed for the formation of new autophagosomes. Finley and her team found that levels of Atg8a were significantly reduced by four weeks of age, a time when the flies are considered middle aged. At the same time, protein aggregates were not efficiently cleared by the cellular clean-up crew and started to accumulate.

Without Atg8a, things went from bad to worse. Damaged proteins tagged for degradation started to pile up early and life expectancy plummeted. The abnormal accumulation of protein aggregates had striking similarities to those seen in the most common human neurodegenerative diseases, says first author Anne Simonsen, Ph.D., a visiting scientist from the University of Oslo, Norway.

When the researchers kept the neuronal levels of Atg8a high, the genetically engineered flies were spared the ravages of time. Promoting the pathway not only prevented the accumulation of protein aggregates but also significantly extended the average lifespan. Our experiments show for the first time genetically that autophagy can sequester and eliminate misfolded and damaged proteins, which accumulate in neurons as normal part of the aging process, says Simonsen, but most importantly they demonstrate that enhancing the clearance of damaged proteins and protein aggregates increases longevity.

Insulin signaling and caloric restriction are two major determinants of longevity and they also impact the activity level of autophagy. Therefore, regulating autophagy, the pathway that directly does the cleanup work, may be the key factor in controlling the aging process, the researchers say. By maintaining the expression of a rate-limiting autophagy gene in the aging nervous system there is a dramatic extension of lifespan and resistance to age-associated oxidative stress, says Finley.


Contact: Gina Kirchweger
858-453-4100 x1340
Salk Institute  

Related biology news :

1. Small animal imaging facility is big boon to research
2. Hebrew SeniorLife researchers search for aging, osteoporosis genes
3. Depression, aging, and proteins made by a virus may all play role in heart disease
4. CU-Boulder worm study sheds light on human aging, inherited diseases
5. UVA researchers explain cell response to skin-damaging UV rays
6. New thoracic imaging approach can pinpoint underlying venous problems
7. Stowers Institutes Xie Lab demonstrates dual intrinsic and extrinsic control of stem cell aging
8. Quantitative PET imaging finds early determination of effectiveness of cancer treatment
9. Genes identified to protect brassicas from damaging disease
10. New test finds diisobutyl phthalate in some cardboard food packaging -- recycling is the issue
11. Sirtris unveils promising, novel SIRT1 activators for treating diseases of aging
Post Your Comments:
Related Image:
Aging gracefully requires taking out the trash
(Date:11/9/2015)... 2015  Synaptics Inc. (NASDAQ: SYNA ), the ... entry into the automotive market with a comprehensive and ... of consumer electronics human interface innovation. Synaptics, industry-leading touch ... the automotive industry and will be implemented in numerous ... , Japan , and ...
(Date:10/29/2015)... , Oct. 29, 2015 Daon, a ... that it has released a new version of its ... in North America have already ... v4.0 also includes a FIDO UAF certified server ... already preparing to activate FIDO features. These customers include ...
(Date:10/27/2015)... In the present market scenario, security is ... industry verticals such as banking, healthcare, defense, electronic gadgets, ... for secure & simplified access control and growing rate ... of bank accounts, misuse of users, , and so ... laptops, and smartphones are expected to provide potential opportunities ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... RALEIGH, N.C. , Nov. 24, 2015  Clintrax Global, Inc., ... Raleigh, North Carolina , today announced that the company has ... earnings represented a 391% quarter on quarter growth posted for Q3 ... Kingdom and Mexico , with the ... place in December 2015. --> United Kingdom ...
(Date:11/24/2015)... , November 24, 2015 SHPG ) announced ... in the Piper Jaffray 27 th Annual Healthcare Conference in ... 1, 2015, at 8:30 a.m. EST (1:30 p.m. GMT). --> ... Financial Officer, will participate in the Piper Jaffray 27 th ... NY on Tuesday, December 1, 2015, at 8:30 a.m. EST (1:30 ...
(Date:11/24/2015)... Nov. 24, 2015  Twist Bioscience, a company ... Leproust, Ph.D., Twist Bioscience chief executive officer, will ... on December 1, 2015 at 3:10 p.m. Eastern ... City. --> --> ... Twist Bioscience is on Twitter. Sign up to ...
(Date:11/24/2015)... - ProMetic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) ("ProMetic" ... , President and Chief Executive Officer of ProMetic, will be ... th Annual Healthcare Conference to be held at the ... st , at 8.50am (ET) and ProMetic,s management team ... presentation will be available live via a webcast accessible at ...
Breaking Biology Technology: