Date:

October 26, 2017

Source:

Harvard T.H. Chan School of Public Health

Summary:

Manipulating
mitochondrial networks inside cells — either by dietary re,striction or by
genetic manipulation that mimics it — may increase lifespan and promote
health, according to new research.

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.

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Materials provided by Harvard T.H. Chan School of Public
Health. Note: Content may be edited for style and length.

Journal Reference:

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