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WHY MITOCHONDRIA MATTER IN BRAIN AGING

As we age, our cells gradually lose their ability to produce energy efficiently and manage stress. The brain is especially vulnerable because it requires large amounts of energy to function properly. Even during normal aging, the brain shows changes such as low-grade inflammation, shrinkage, and slower communication between neurons.

MITOCHONDRIAL STRESS AND CHRONIC INFLAMMATION

With advancing age, mitochondria produce higher levels of reactive oxygen species (ROS). At the same time, the body’s antioxidant defenses weaken. Excess ROS damages mitochondrial DNA, proteins, and membranes, reducing energy production and triggering a cycle of ongoing cellular stress.

Damaged mitochondria can release internal components, including mitochondrial DNA and calcium, into the cell and bloodstream. These molecules act as danger signals that activate the immune system and promote inflammation. Because this inflammatory process begins inside the mitochondria, it is referred to as mito-inflammation.

MELATONIN: MORE THAN A SLEEP HORMONE

Melatonin is commonly known for regulating sleep, but most melatonin in the body is produced inside cells, particularly within mitochondria. Only a small portion comes from the pineal gland. Unlike nighttime melatonin release, mitochondrial melatonin production occurs continuously and is not dependent on the light–dark cycle.

Melatonin levels decline with age. This decline is closely linked to worsening mitochondrial function, rising oxidative stress, and increased inflammation, creating a feedback loop that accelerates cellular aging.†

HOW MELATONIN PROTECTS MITOCHONDRIA

Melatonin protects mitochondria in several important ways. It directly neutralizes reactive oxygen species and also increases the activity of the body’s own antioxidant enzymes. These actions help preserve mitochondrial structure and maintain energy production.

Melatonin also stabilizes cardiolipin, a key lipid required for proper mitochondrial membrane structure. Experimental studies show that melatonin improves mitochondrial shape, reduces oxidative damage, and supports communication between healthy and injured cells.

SUPPORTING METABOLISM AND PROTEIN QUALITY

Under disease-related stress, cells often shift away from mitochondrial energy production. This reduces the availability of key molecules needed for mitochondrial melatonin synthesis, weakening antioxidant protection. Supplementing melatonin may help restore healthier mitochondrial metabolism. †

Melatonin also supports protein quality control within mitochondria. It activates protective stress-response pathways, enhances removal of damaged mitochondria, and reduces inflammatory signaling linked to mitochondrial DNA release. †

CLINICAL RELEVANCE AND FUTURE OUTLOOK

As populations age, preventing or delaying neurodegenerative disease has become a major clinical priority. While no single therapy can reverse brain aging, melatonin is a promising candidate due to its strong safety profile and wide-ranging effects on mitochondrial health. †

Future clinical trials are needed to determine whether melatonin supplementation can support long-term brain health. Understanding how melatonin interacts with mitochondrial signaling pathways may help guide new strategies for healthy aging. †

REFERENCE:

Melatonin and mitochondrial stress: New insights into age-related neurodegeneration.
Neural Regeneration Research
April, 2026
Carloni, Silvia et al.

† These statements have not been evaluated by the Food and Drug administration.
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