Manipulating mitochondrial networks could promote healthy aging

October 26, 2017

Boston, MA - Manipulating mitochondrial networks inside cells -- either by dietary restriction or by genetic manipulation that mimics it--may increase lifespan and promote health, according to new research from Harvard T.H. Chan School of Public Health.

The study, published online October 26, 2017 in Cell Metabolism, sheds light on the basic biology involved in cells' declining ability to process energy over time, which leads to aging and age-related disease, and how interventions such as periods of fasting might promote healthy aging.

Mitochondria -- the energy-producing structures in cells -- exist in networks that dynamically change shape according to energy demand. Their capacity to do so declines with age, but the impact this has on metabolism and cellular function was previously unclear. In this study, the researchers showed a causal link between dynamic changes in the shapes of mitochondrial networks and longevity.

The scientists used C. elegans (nematode worms), which live just two weeks and thus enable the study of aging in real time in the lab. Mitochondrial networks inside cells typically toggle between fused and fragmented states. The researchers found that restricting the worms' diet, or mimicking dietary restriction through genetic manipulation of an energy-sensing protein called AMP-activated protein kinase (AMPK), maintained the mitochondrial networks in a fused or "youthful" state. In addition, they found that these youthful networks increase lifespan by communicating with organelles called peroxisomes to modulate fat metabolism.

"Low-energy conditions such as dietary restriction and intermittent fasting have previously been shown to promote healthy aging. Understanding why this is the case is a crucial step towards being able to harness the benefits therapeutically," said Heather Weir, lead author of the study, who conducted the research while at Harvard Chan School and is now a research associate at Astex Pharmaceuticals. "Our findings open up new avenues in the search for therapeutic strategies that will reduce our likelihood of developing age-related diseases as we get older."

"Although previous work has shown how intermittent fasting can slow aging, we are only beginning to understand the underlying biology," said William Mair, associate professor of genetics and complex diseases at Harvard Chan School and senior author of the study. "Our work shows how crucial the plasticity of mitochondria networks is for the benefits of fasting. If we lock mitochondria in one state, we completely block the effects of fasting or dietary restriction on longevity."

Next steps for the researchers including testing the role mitochondrial networks have in the effect of fasting in mammals, and whether defects in mitochondrial flexibility might explain the association between obesity and increased risk for age-related diseases.
-end-
Other Harvard Chan authors included Pallas Yao, Caroline Escoubas, Renata Goncalves, Kristopher Burkewitz, and Raymond Laboy.

Funding for the study came from the Lawrence Ellison Medical Foundation (U54CA155626), the Glenn Foundation for Medical Research, the National Institutes of Health (1R01AG044346, 1R01AG045351), and the American Diabetes Association/Canadian Diabetes Association PF-3-13-4342.

"Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling," Heather J. Weir, Pallas Yao, Frank K. Huynh, Caroline C. Escoubas, Renata L. Goncalves, Kristopher Burkewitz, Raymond Laboy, Matthew D. Hirschey, and William B. Mair, Cell Metabolism, online October 26, 2017, doi: 10.1016/j.cmet.2017.09.024

Visit the Harvard Chan School website for the latest news, press releases, and multimedia offerings.

Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere. As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people's lives -- not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan School teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses. Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America's oldest professional training program in public health.

Harvard T.H. Chan School of Public Health

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.