Nav: Home

Mitochondria may metabolize ADP differently in aging muscle, despite exercise resistance

March 13, 2018

Most adults reach their peak levels of muscle mass in their late 30s or early 40s. Even for those who exercise regularly, strength and function start to decline after that point. For those who don't exercise, the drops can be dramatic. Now, a study of twenty men published March 13 in the journal Cell Reports provides new clues about the cellular mechanisms of aging muscles, showing a key role for how mitochondria, the powerhouses of the cell, process ADP, which provides energy to cells.

ADP, or adenosine diphosphate, plays a role in how our cells release and store energy. But previous lab models that have looked at the mechanisms of aging in human cells have not included ADP. When ADP is metabolized in the mitochondria, it stimulates cellular respiration and decreases reactive oxidative species (ROS; also known as free radicals). Higher ROS levels are linked to damage in different components of the cell, a process also called oxidative stress.

In the study, the investigators developed an in vitro system employing individual muscle fibers taken from muscle biopsies. The fibers were put into a system in which mitochondrial function and respiration could be measured across a range of ADP concentrations that are relevant to those found in the human body. "The way people normally measure ROS is in a system that has ADP removed," says senior author Graham Holloway, an associate professor at the University of Guelph in Ontario. "But biologically, we always have ADP in the system. We started to think that maybe how we get ADP into the mitochondria is important for aging."

In the first part of the paper, the researchers compared muscle from ten healthy men in their 20s with muscle from ten healthy men in their early 70s. They found that there was an 8- to 10-fold decrease in ADP sensitivity, and therefore, when ADP was added to the system, there was a 2- to 3-fold higher rate of ROS emission in the muscle taken from the older men. ROS levels were determined by measuring emissions of hydrogen peroxide, a byproduct of activity in the cell.

The findings suggested that mitochondrial ADP sensitivity was somehow impaired in the muscles of the older men and that increased levels of ROS were contributing to sarcopenia, or the degenerative loss of muscle mass. "The magnitude of change was quite striking to us," Holloway explains. "For humans, it's remarkable to have such a big difference."

In the second part, the older men undertook a program of supervised resistance training, which included leg presses and upper-body exercises. But, after 12 weeks, there were no changes in the levels of hydrogen peroxide emitted, suggesting no improvements in age-associated cellular stress.

"This doesn't mean there's no hope for building strength in aging muscle," Holloway says. "I actually think that endurance training would be potentially beneficial, because we know with that kind of training you get increases in mitochondrial content." Endurance training includes aerobic exercise like cycling and swimming. "Moving forward, we plan to look at other types of exercise, to see if it can improve the dynamic response of mitochondria to ADP," he adds.

Other future work will use rodent models to delve into the cause-and-effect relationships of the molecular mechanisms of ADP metabolism. The investigators also plan to extend their studies to looking at different types of exercise in aging women. Early research in healthy young people has indicated that there are differences in sensitivity to ADP between men and women.
This study was funded by the Natural Sciences and Engineering Research Council of Canada and TI Food and Nutrition, a public-private partnership on precompetitive research in food and nutrition.

Cell Reports, Holloway et al. "Age-associated impairments in mitochondrial ADP sensitivity contribute to redox stress in senescent human skeletal muscle."

Cell Reports (@CellReports), published by Cell Press, is a weekly open-access journal that publishes high-quality papers across the entire life sciences spectrum. The journal features reports, articles, and resources that provide new biological insights, are thought-provoking, and/or are examples of cutting-edge research. Visit: To receive Cell Press media alerts, contact

Cell Press

Related Aging Articles:

Brain development and aging
The brain is a complex organ -- a network of nerve cells, or neurons, producing thought, memory, action, and feeling.
Aging gracefully in the rainforest
In an article that appears in the current issue of Evolutionary Anthropology, researchers synthesize over 15 years of theoretical and empirical findings from long-term study of the Tsimane forager-farmers.
Reversing aging now possible!
DGIST's research team identified the mechanism of reversible recovery of aging cells by inducing lysosomal activation.
Brain-aging gene discovered
Researchers at Columbia University Medical Center have discovered a common genetic variant that greatly affects normal brain aging in older adults.
Aging can be good for you (if you're a yeast)
It's a cheering thought for anyone heading towards their golden years.
How eating less can slow the aging process
New research shows why calorie restriction made mice live longer and healthier lives.
Turning back the aging clock
By boosting genes that destroy defective mitochondrial DNA, researchers can slow down and potentially reverse an important part of the aging process.
Insilico Medicine launches a deep learned biomarker of aging, Aging.AI 2.0 for testing
Insilico Medicine, Inc., a company applying latest advances in deep learning to biomarker development, drug discovery and aging research, launched Aging.AI 2.0.
Substance with the potential to postpone aging
The coenzyme NAD+ plays a main role in aging processes.
What does a healthy aging cat look like?
Just as improved diet and medical care have resulted in increased life expectancy in humans, advances in nutrition and veterinary care have increased the life span of pet cats.

Related Aging Reading:

The Grace in Aging: Awaken as You Grow Older
by Kathleen Dowling Singh (Author)

Learn to use your later years for awakening and spiritual growth.

Encouraging, inspiring, and practical, The Grace in Aging invites all those who have ever experienced spiritual longing to awaken in their twilight years. Since aging, in and of itself, does not lead to spiritual maturity, The Grace in Aging suggests and explores causes and conditions that we can create in our lives, just as we are living them, to allow awakening to unfold—transforming the predictable sufferings of aging into profound opportunities for growth in clarity, love, compassion, and peace.... View Details

Aging: An Apprenticeship
by Nan Narboe (Editor)

Nan Narboe's 56 thoughtfully selected essays offer an intimate and lyrical account of aging through the decades.

Authors Judy Blume, Andrew McCarthy, Gloria Steinem, Donald Hall, David Shields, Ursula K. Le Guin and others draw from their own experiences, describing a specific decade's losses and gains to form a complex and unflinching portrait of the years from nearing fifty to ninety and beyond.

In six sections, these detail-rich essays paint an accessible picture of nearing 50, the 50s, 60s, 70s, 80s, the 90s and beyond with equal parts humor... View Details

Aging Well: Surprising Guideposts to a Happier Life from the Landmark Harvard Study of Adult Development
by George E. Vaillant (Author)

In a unique series of studies, Harvard University has followed 824 subjects from their teens to old age. Professor George Vaillant now uses these to illustrate the surprising factors involved in reaching happy, healthy old age. View Details

Aging as a Spiritual Practice: A Contemplative Guide to Growing Older and Wiser
by Lewis Richmond (Author)

The bestselling author of Work as a Spiritual Practice presents a user’s life guide to aging well and making every year fulfilling and transformative.

Everything changes. For Zen Buddhist priest and meditation teacher Lewis Richmond, this fundamental Buddhist tenet is the basis for a new inner road map that emerges in the later years, charting an understanding that can bring new possibilities and a wealth of appreciation and gratitude for the life journey itself.

Aging as a Spiritual Practice is a wise, compassionate book that guides readers through the... View Details

Aging: The Fulfillment of Life
by Henri J.M. Nouwen (Author), Walter J. Gaffney (Author)

We are all aging. We are each a spoke on the great wheel of life, part of the ongoing cycle of growth. In Aging, Henri J.M. Nouwen and Walter J. Gaffney share some moving and inspirational thoughts on what aging means (and can mean) to all of us, whether we're in our youth, middle age, or later years.

Enhanced by some eighty-five photographs depicting various scenes from life and nature, this book shows how to make the later years a source of hope rather than a time of loneliness -- a way out of darkness into the light. "Aging," the authors write, "is not a reason for... View Details

Mindful Aging: Embracing Your Life After 50 to Find Fulfillment, Purpose, and Joy
by Andrea Brandt (Author)

Don't let the ominous perception of "aging" - a lack of purpose, feeling irrelevant and under-used, having nothing to do - take control of you and your life.

You have the power to change how you grow older. This book will show you how.

Renowned psychotherapist and aging expert Andrea Brandt, PhD, MFT, helps you throw out the old stereotypes about getting older and move toward the welcoming new evidence that your future is alive with possibility, providing steps to thrive today and into your golden years.

The acclaimed Mindful Aging is full of exercises and tools... View Details

Healthy Aging: A Lifelong Guide to Your Well-Being
by Andrew Weil M.D. (Author)

In each of his widely acclaimed, best-selling books, Dr. Andrew Weil has been an authoritative and companionable guide through a uniquely effective combination of traditional and nontraditional approaches to health and healthy living. Now he gives us a book about aging that is unlike any other. Drawing on the new science of biogerontology (the biology of aging) as well as on the secrets of healthy longevity — diet, activity and attitude — Dr. Weil explains that there are a myriad of things we can do to keep our bodies and minds in good working order through all phases of life.... View Details

Aging Backwards: Reverse the Aging Process and Look 10 Years Younger in 30 Minutes a Day
by Miranda Esmonde-White (Author)

PBS fitness personality on Classical Stretch and creator of the fitness phenomenon Essentrics, Miranda Esmonde-White offers an eye-opening guide to anti-aging that provides essential tools to help anyone turn back the clock and look and feel younger no matter what age.

Miranda Esmonde-White trains everyone from prima ballerinas to professional hockey players to Cerebral palsy patients: what do they all have in common? All of these people are hoping to heal their bodies, prevent further injury, and move optimally and without pain. In fact, they have... View Details

Aging with Grace: What the Nun Study Teaches Us About Leading Longer, Healthier, and More Meaningful Lives
by David Snowdon (Author)

In 1986 Dr. David Snowdon, one of the world’s leading experts on Alzheimer’s disease, embarked on a revolutionary scientific study that would forever change the way we view aging—and ultimately living. Dubbed the “Nun Study” because it involves a unique population of 678 Catholic sisters, this remarkable long-term research project has made headlines worldwide with its provocative discoveries.
Yet Aging with Grace is more than a groundbreaking health and science book. It is the inspiring human story of these remarkable women—ranging in age from 74 to 106—whose... View Details

How to Care for Aging Parents, 3rd Edition: A One-Stop Resource for All Your Medical, Financial, Housing, and Emotional Issues
by Virginia Morris (Author), Jennie Chin Hansen RN MSN FAAN (Foreword)

“The bible of eldercare”—ABC World News. “An indispensable book”—AARP. “A compassionate guide of encyclopedic proportion”—The Washington Post. And, winner of a Books for a Better Life Award. How to Care for Aging Parents is the best and bestselling book of its kind, and its author, Virginia Morris, is the go-to person on eldercare for the media, appearing on Oprah, TODAY, and Good Morning America, among many other outlets.

How to Care for Aging Parents is an authoritative, clear, and comforting source of advice and... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Consequences Of Racism
What does it mean to be judged before you walk through the door? What are the consequences? This week, TED speakers delve into the ways racism impacts our lives, from education, to health, to safety. Guests include poet and writer Clint Smith, writer and activist Miriam Zoila Pérez, educator Dena Simmons, and former prosecutor Adam Foss.
Now Playing: Science for the People

#466 Wildfire
This week we're talking about fire: in particular, wildfires. How they spread and how we manage them, but also the deeper history of wildfires on our planet and how they've been shaping our world for a long, long time. We speak with Andrew Scott, Emeritus Professor of Geology at Royal Holloway, University of London, about his book "Burning Planet: The Story of Fire Through Time", learning about wildfire on our planet now and in deep history. And we catch up with Caroline Weinberg, interm executive director of the March for Science organization, about this year's march on April 14.