Exercise Might Reverse Muscle Aging, New Research Suggests. 3 Exercises to Try

New research suggests that exercise influences a cellular signaling pathway that helps clear out damaged muscle proteins.

Exercise has a well-earned reputation as one of the best strategies for protecting muscles from age-related changes. After age 30, inactive adults can lose 3% to 5% of their muscle mass per decade, and the pace picks up after 60. Fibrous tissue and fat gradually work their way into what remains, stiffening the muscle over time.

Now, early research in fruit flies and mice, published in the Proceedings of the National Academy of Sciences, might help explain how exercise benefits aging muscles. Researchers at Duke-NUS Medical School in Singapore found that working out does more than make muscles grow. It might also reverse age-related muscle changes. Exercise influences a key biological pathway, the FOXO-DEAF1-mTORC1 axis, that helps muscle cells repair and clear out damaged proteins that could otherwise weaken them.

“We believe that this pathway represents a highly promising therapeutic target for combating age-related muscle wasting, termed as sarcopenia,” says Hong-Wen Tang, PhD, senior author of the study and an assistant professor in the Cancer and Stem Cell Biology Programme at Duke-NUS Medical School.

A Pathway to Muscle Health

This study focused on fruit flies and mice. More research is of course needed to figure out how this might work in people, though human trials have already linked exercise to changes in mTOR signaling.

In this research, aged mice ran on treadmills and on resistance wheels, adding to the evidence that both endurance and strength work help you maintain healthy muscle, by building it up and by slowing muscle aging.

“As we age, our muscle cells slowly lose their ability to self-repair because a transcription factor called DEAF1 becomes abnormally overexpressed,” says Tang. “This accumulation pushes a growth-regulating protein complex, known as mTORC1, into chronic overdrive.”

Muscle proteins are constantly building and breaking down. A little boost of mTORC1 isn’t always a bad thing. However, long-term elevations in mTORC1 activity can inhibit the natural cellular cleanup processes that remove damaged muscle proteins.

“Over time, this imbalance traps cellular garbage inside the cells, causing muscle wasting and weakness,” explains Tang.

In older animals, raising DEAF1 levels made muscles weaker. Aged fruit flies with elevated DEAF1 struggled to climb the side of a vial, a standard measure of muscle function. Younger flies were unaffected, which suggests it’s aging muscle specifically that becomes vulnerable to this shift.

Here’s where exercise comes in. Researchers found that in the lab animals, exercise ramped up a family of molecular switches – FOXO – that suppressed DEAF1, normalizing mTORC1 activity to help preserve muscle function. FOXO activity in muscles tends to decline with age, reducing control over DEAF1 and mTORC1.

“Regular physical activity fundamentally resets this broken system,” said Tang.

Here’s why: Physical activity places a healthy mechanical and metabolic stress on skeletal muscles, triggering intracellular signaling cascades that act like alarms to activate and mobilize FOXO proteins. Those FOXO proteins then bind to the gene responsible for DEAF1, acting as a powerful molecular brake to slow it down. As a result, mTORC1 activity returns to normal.

“With the self-cleaning machinery restored, aging muscles can efficiently clear out accumulated cellular debris, repair structural damage, and maintain functional strength[fuhngk-shuh-nl strength]nounStrength that translates to everyday tasks and movements.Learn MoreClose, effectively keeping muscles stronger for longer,” says Tang.

Muscle Strategies for Longevity 

This study focused on fruit flies and mice. More research is of course needed to figure out how this might work in people, though there are certainly human studies connecting exercise to altered mTOR signaling.

We may not know exactly which exercises best target the FOXO-DEAF1-mTORC1 axis, but we do have clues. This research, which exposed animals to both aerobic and strength training[strength tray-ning]nounResistance-based exercise to build muscle and support healthy aging.Learn MoreClose, adds to the evidence suggesting that both help you maintain healthy muscles both by building them up and slowing muscle aging.

“Our findings suggest that both aerobic (endurance) exercise and resistance (strength) training are beneficial for muscle health,” notes Tang. “Each type of exercise activates the body’s protective FOXO pathway in slightly different ways, and doing a combination of both is likely to provide the greatest benefit.”

Three ways to start turning back the clock on muscle aging:

●  Strength training: Lifting weights is a classic for a reason. A network meta-analysis of 42 randomized trials in nearly 3,800 older adults with sarcopenia found that resistance exercise improved physical function, and that adding balance training[bal-uhns trey-ning]nounExercises that improve coordination, reduce fall risk, and enhance mobility.Learn MoreClose to resistance work was the most effective combination of all for gait speed and for getting out of a chair. For ideas on structuring the resistance half, the American College of Sports Medicine released its 2026 resistance training guidelines in March, its first update in 17 years.

● Aerobic training: Whether you prefer long, winding runs or short sprints, aerobic exercise can help rejuvenate your muscles. A systematic review pooling data from nearly 6,000 people found that continuous endurance training, high-intensity interval training, and sprint interval training all increased muscle mitochondrial content by 23% to 27%. The researchers also found that the capacity to adapt to training holds up across the lifespan, regardless of age, sex, or disease. That matters, since muscle mitochondria[mahy-tuh-kon-dree-uh]nounOrganelles in cells responsible for producing energy (ATP), often called the powerhouse of the cell.Learn MoreClose, the cellular powerhouses that produce energy to power muscle movement, tend to decline with aging, contributing to size and strength losses.

And it’s never too late to start. In a study of adults in their 80s who were living with conditions like hypertension and osteoarthritis, interval training improved muscle protein synthesis and mitochondrial capacity, possibly by acting on a different cellular signaling pathway, the phosphoinositide 3-kinase-Akt-mTOR route that helps stimulate muscle growth. Participants completed three 16.5-minute sessions per week for four weeks. Each session opened with a 2-minute warmup of unloaded cycling, then five 1-minute efforts on a stationary bike at 100% to 115% of their maximum load, each followed by 90 seconds of unloaded pedaling. A 2-minute cooldown closed it out. No adverse events were reported.

●  Blood flow[bluhd floh]nounThe movement of blood through the circulatory system, delivering oxygen and nutrients to organs and tissues to support energy, healing, and overall health.Learn MoreClose restriction (BFR) training: Consider adding a new accessory to your workout. In a 2022 review, researchers proposed that BFR, which uses a cuff to reduce blood flow in target muscles during aerobic or resistance exercise, could help counter age-related muscle loss through its effects on blood vessels, hormones, tissue oxygen levels, muscle fiber recruitment, and muscle stem cells.

A meta-analysis of 14 trials in healthy adults over 60 found that low-load BFR training, at 20% to 40% of 1-rep max, produced better strength gains than the same light loads without the cuff. Heavy lifting still outperformed both, so BFR is best understood as a bridge rather than a replacement. BFR appears to be safe for many people, but always check with your doctor before trying it and consider working with a trainer or other professional who can help you do it safely. Need somewhere to start? Try Arthur Brooks’ BFR workout.

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