The absence of a single protein spurs muscle aging in mice

June 22, 2016

One of the alterations that most affects the quality of life of the elderly is muscle wastage and the resulting loss of strength, a condition known as sarcopenia. At about 55 years old, people begin to lose muscle mass, this loss continues into old age, at which point it becomes critical. The underlying causes of sarcopenia are unknown and thus no treatment is available for this condition. A study at the Institute for Research in Biomedicine (IRB Barcelona) done in collaboration with the University of Barcelona (UB) and the CIBER's area of Diabetes and Associated Metabolic Diseases (CIBERDEM) has discovered that Mitofusin 2 is required to preserve healthy muscles in mice. In the paper, which has been published today in The EMBO Journal, these researchers indicate that this protein could serve as a therapeutic target to ameliorate sarcopenia in the elderly.

Headed by Antonio Zorzano, coordinator of the Molecular Medicine Programme at IRB Barcelona, and UB and ICREA Academia professor, the scientists observed that during aging mice specifically lose the expression of Mitofusin 2 in muscle. They demonstrate that low activity of this protein in 24-month old mice (the equivalent of a person aged 80) is directly associated with muscle wastage and the sarcopenia observed. The scientists confirm the link between the loss of Mitofusin 2 and muscle aging when the expression of the protein is suppressed in the muscles of 6-month-old animals (equivalent to a person of 30) as these animals showed accelerated aging, reproducing thus muscle conditions of aged mice.

"Over five years we have collected sufficiently significant evidence that demonstrates the contribution of Mitofusin 2 to the maintenance of good muscle health in mice and that allows us to consider a therapeutic strategy for sarcopenia," explains the first author of the article David Sebastián, an IRB Barcelona and CIBERDEM researcher. "Sarcopenia is not a minor issue because it impedes some elderly people from going about their everyday lives," explains Antonio Zorzano, IRB Barcelona researcher and head of the Complex Metabolic Diseases and Mitochondria Lab. "If we want to boost the health of the elderly then this problem has to be addressed," he stresses. The world's population is aging. The United Nations estimates that in 2050 there will be 2.1 billion people over 60, a figure that accounts for 22% of the world population. Currently, this figure stands at 12%.

Dr. Zorzano's lab is running a study in collaboration with physicians working in geriatric medicine at Sant Joan de Déu Hospital to demonstrate that Mitofusin 2 is also repressed in human aging. "We need to demonstrate this if we want to translate our findings to clinical practice," he says. In addition, this group also has the technology ready to search for pharmacological agents capable of boosting Mitofusin 2 activity.

The researcher also explains another phenomenon of extreme muscle degeneration called cachexia, a condition associated with disease, especially cancer. "If we can find a molecule that improves muscle status, it should be tested against cachexia in cancer patients," states Zorzano, "because in some cases this is the real cause of death in this patient group."

The molecular mechanisms behind muscle aging

Mitofusin 2 is a mitochondrial protein involved in ensuring the correct function of mitochondria, and it has several activities related to autophagy, a crucial process for the removal of damaged mitochondria. The loss of Mitofusin 2 impedes the correct function of mitochondrial recycling and consequently damaged mitochondria accumulate in muscle cells.

Thanks to this study, the researchers have also identified and described an autophagy rescue system which kicks in regardless of Mitofusin 2 levels and allows cells to partially recover the mitochondrial recycling system in skeletal muscle. The scientists suggest that this could serve as an alternative metabolic mechanism used by Mitofusin to increase skeletal muscle autophagy and to maintain a healthier mitochondrial system.
-end-
This study has been supported by funding from the Ministry of the Economy and Competiveness, the Government of Catalonia, the CIBERDEM Centre and the European project DIOMED, part of the INTERREG-SUDOE-FEDER programme, which is led by Antonio Zorzano.

Reference article:

Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway

David Sebastián, Eleonora Sorianello, Jessica Segalés, Andrea Irazoki, Vanessa Ruiz-Bonilla, David Sala, Evarist Planet, Antoni Berenguer-Llergo, Juan Pablo Muñoz, Manuela Sánchez-Feutrie, Natàlia Plana, María Isabel Hernández-Álvarez, Antonio L. Serrano, Manuel Palacín, and Antonio Zorzano

The EMBO Journal (22 June 2016) doi: 10.15252/embj.201593084

Institute for Research in Biomedicine (IRB Barcelona)

Related Aging Articles from Brightsurf:

Surprises in 'active' aging
Aging is a process that affects not only living beings.

Aging-US: 'From Causes of Aging to Death from COVID-19' by Mikhail V. Blagosklonny
Aging-US recently published ''From Causes of Aging to Death from COVID-19'' by Blagosklonny et al. which reported that COVID-19 is not deadly early in life, but mortality increases exponentially with age - which is the strongest predictor of mortality.

Understanding the effect of aging on the genome
EPFL scientists have measured the molecular footprint that aging leaves on various mouse and human tissues.

Muscle aging: Stronger for longer
With life expectancy increasing, age-related diseases are also on the rise, including sarcopenia, the loss of muscle mass due to aging.

Aging memories may not be 'worse, 'just 'different'
A study from the Department of Psychological & Brain Sciences in Arts & Sciences adds nuance to the idea that an aging memory is a poor one and finds a potential correlation between the way people process the boundaries of events and episodic memory.

A new biomarker for the aging brain
Researchers at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan have identified changes in the aging brain related to blood circulation.

Scientists invented an aging vaccine
A new way to prevent autoimmune diseases associated with aging like atherosclerosis, Alzheimer's disease, and Parkinson's disease was described in the article.

The first roadmap for ovarian aging
Infertility likely stems from age-related decline of the ovaries, but the molecular mechanisms that lead to this decline have been unclear.

Researchers discover new cause of cell aging
New research from the USC Viterbi School of Engineering could be key to our understanding of how the aging process works.

Deep Aging Clocks: The emergence of AI-based biomarkers of aging and longevity
The advent of deep biomarkers of aging, longevity and mortality presents a range of non-obvious applications.

Read More: Aging News and Aging Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.