Sarcopenia, Mitochondrial Health and Muscle Ageing.
- Alastair Hunt
- Jun 13
- 6 min read
Updated: Jun 25
As we grow older, many of us notice a gradual loss of strength, reduced stamina, and increasing frailty. This condition, known as sarcopenia, is not simply about ageing muscles getting weaker; it involves complex interactions between our cells’ energy production systems - specifically the mitochondria - and the processes that regulate muscle health.
As ever, please talk to your doctor or medical practitioner most familiar with your medical history before implementing any changes in diet, exercise or lifestyle, especially if you are under treatment. Links to all studies at bottom of page.
What Is Sarcopenia?
Sarcopenia refers to the progressive loss of skeletal muscle mass and function, a hallmark of biological ageing that begins subtly in our 30s and accelerates after age 60. By age 80, individuals can lose up to 30% of their muscle mass. While this decline can be influenced by inactivity or poor nutrition, it is primarily driven by changes in internal cellular processes -especially those involving mitochondria.
These muscle changes increase the risk of falls, fractures and chronic diseases such as type 2 diabetes. But the root of sarcopenia goes deeper than just visible muscle shrinkage - it’s embedded in how our muscle cells produce and manage energy.
Mitochondria: The Powerhouses Behind Muscle Health
Mitochondria are tiny structures in our cells responsible for producing ATP, the molecule that fuels most cellular activities, including muscle contraction and repair. With age, these powerhouses become less efficient. Their ability to convert nutrients into energy drops, they produce more reactive oxygen species (ROS) - damaging by-products of energy production - and they become less capable of self-repair.
As mitochondria age, their internal structures (like cristae) become disorganised. This disarray reduces energy generation and contributes to muscle fatigue. Furthermore, ageing muscle cells often show reduced mitochondrial numbers and altered positioning within muscle fibres, disrupting energy supply where it’s needed most.
Why Energy Decline Matters in Ageing Muscles
When mitochondrial efficiency drops, ATP levels fall, leading to slower protein synthesis and impaired muscle repair. This process sets off a cascade of problems: damaged proteins accumulate, muscle fibres become more susceptible to stress and the body struggles to replace old or dysfunctional mitochondria through a process called mitophagy.
Two key signalling systems are at play here - AMPK and mTOR. AMPK acts like an energy gauge, triggering autophagy and mitophagy when cellular energy is low. However, AMPK activity declines with age, meaning fewer damaged mitochondria are cleared out. At the same time, mTOR - responsible for cell growth and protein production - remains active, further inhibiting autophagy. This imbalance leads to muscle degradation rather than repair.
How Mitochondrial Dysfunction Leads to Muscle Loss
Several mechanisms link mitochondrial breakdown to muscle atrophy:
Reduced ATP: Impairs muscle repair and function.
Increased ROS: Damages DNA and proteins, promoting cell death.
Inflammatory triggers: Heighten immune responses that degrade tissue.
Impaired calcium handling: Affects muscle contraction.
Dysfunctional protein recycling: Leads to buildup of defective proteins.
These effects are compounded by changes in gene expression. As we age, genes linked to mitochondrial function are downregulated, while stress and inflammation genes are upregulated. This reprogramming further weakens cellular repair mechanisms.
The Vicious Cycle of ROS and DNA Damage
Ageing mitochondria produce more ROS, a natural by-product of energy production. ROS include unstable molecules like hydrogen peroxide and superoxide that, in small amounts, play helpful roles in cellular signalling. However, in excess, they become harmful, damaging proteins, fats and DNA - particularly mitochondrial DNA.. Over time, this damage impairs the mitochondria’s ability to function effectively, deepening the decline in energy production and muscle integrity.
This leads us to an important and ongoing debate in ageing biology: is mitochondrial dysfunction the cause of increased ROS, or is ROS overproduction the trigger for mitochondrial decline? In other words, is this a chicken-or-egg scenario?
The evidence suggests that both mechanisms feed into one another, creating a feedback loop. Damaged mitochondria produce more ROS, which further harms the mitochondrial structure and its genetic material. This, in turn, leads to more dysfunction and even greater ROS release. Over time, the balance tips too far, and the cell’s antioxidant defences - normally able to neutralise small bursts of ROS - can no longer keep up. The result is a cycle of escalating damage that contributes directly to the muscle wasting and weakness seen in sarcopenia.
Lifestyle Strategies to Support Mitochondrial Health
Encouragingly, there are several lifestyle habits shown to support mitochondrial function and potentially mitigate age-related muscle loss:
Regular physical activity, particularly endurance exercise, stimulates mitochondrial biogenesis by activating a protein called PGC-1α. This not only boosts energy production but can also reverse some age-related genetic changes in muscle cells.
Exercise also enhances AMPK activity, a key energy-sensing pathway that supports autophagy - the cellular process of clearing out damaged components - and reduces harmful ROS accumulation.
Sufficient protein intake is recommended for older adults to counteract the reduced muscle protein synthesis that occurs with age. Balanced meals that include both plant and animal protein sources may be beneficial.
Dietary antioxidants, such as those found in colourful fruits, vegetables, nuts, and whole grains, can help reduce oxidative stress and support mitochondrial function. These include vitamins C and E, polyphenols and flavonoids.
Intermittent fasting and caloric moderation, though not universally appropriate, may activate AMPK pathways and improve mitochondrial resilience in some individuals. Notably, leading longevity researchers like Drs Luigi Fontana and Valter Longo caution against excess protein intake and promote caloric restriction a part of a longevity promoting lifestyle.
Together, these habits form the basis of what researchers now refer to as “mitochondrial hygiene” - a set of practices that protect and preserve cellular energy systems as we age.
Final Thoughts
The age-related loss of muscle mass isn’t simply a product of getting older, it reflects a deep, intricate decline in how our cells manage energy. As this review highlights, mitochondria sit at the heart of this transformation.
Understanding their role in sarcopenia not only sheds light on why strength and vitality wane with age but also offers hope. By targeting mitochondrial health - through daily movement, sufficient protein, an antioxidant diet and strategies to enhance mitochondrial clearance - we may slow, or even reverse, the physical decline so often accepted as inevitable.
Whether your interest is in sarcopenia, longevity, to beat chronic illness or to enhance your mental health and well-being, our consultations and programs deliver results that are tailored to your needs.
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Stay Healthy,
Alastair
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Related Studies and Resources
Kamarulzaman NT, Makpol S. The link between Mitochondria and Sarcopenia. J Physiol Biochem. 2025 Feb;81(1):1-20. doi: 10.1007/s13105-024-01062-7. Epub 2025 Feb 19. PMID: 39969761; PMCID: PMC11958477.
Song L, Xue J, Xu L, Cheng L, Zhang Y, Wang X. Muscle-specific PGC-1α modulates mitochondrial oxidative stress in aged sarcopenia through regulating Nrf2. Exp Gerontol. 2024 Aug;193:112468. doi: 10.1016/j.exger.2024.112468. Epub 2024 May 28. PMID: 38801840.
Leduc-Gaudet JP, Hussain SNA, Barreiro E, Gouspillou G. Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging. Int J Mol Sci. 2021 Jul 30;22(15):8179. doi: 10.3390/ijms22158179. PMID: 34360946; PMCID: PMC8348122.
Ferri E, Marzetti E, Calvani R, Picca A, Cesari M, Arosio B. Role of Age-Related Mitochondrial Dysfunction in Sarcopenia. Int J Mol Sci. 2020 Jul 23;21(15):5236. doi: 10.3390/ijms21155236. PMID: 32718064; PMCID: PMC7432902.
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