We are all familiar with how integral the mitochondria are in producing the energy needed for our body to meet the demands we place on it. However, for decades, scientists have debated how mitochondria adapt as we age. Some studies show major declines in their ability to make energy, while others suggest little change, leaving the field divided. In this issue of AJP: Endocrinology and Metabolism, this editorial focus highlights new work from the lab of George Brooks, which enlightened our understanding of lactate metabolism. Here work from Leija, Vázquez-Medina, and Brooks (2025), “Resilience of the Mitochondrial Reticulum in Aging”, now brings fresh insight to this long-standing debate of mitochondrial adaptation with age.
Using skeletal muscle from young (4 months) and old (24 months) mice, researchers carefully examined how mitochondrial function and structure changes with age. Surprisingly, authors found that the basic ability of mitochondria to produce energy was largely preserved. Measures of oxidative phosphorylation and coupling efficiency showed no major decline, challenging the view that aging inevitably causes energy failure in mitochondria.
Instead, the major differences between young and old muscle appeared in mitochondrial shape, structure, and organization. Older mice showed reduced levels of key transport proteins, lower activity of enzymes that help fuel metabolism, and altered regulators of mitochondrial remodelling. 2-D and 3-D imaging revealed that the normally interconnected mitochondrial “reticulum” became more fragmented with age, with shorter branches and simpler networks. Importantly, mitochondrial content—the total amount—did not change. This means the problem may lie not in how many mitochondria there are, but in how they are connected and remodelled.
This editorial focus stresses the importance of these findings. They suggest that aging may affect mitochondria more by changing their architecture and dynamics than by damaging their energy-producing machinery. This shift in perspective could reshape how we think about the role of mitochondria in aging and disease.
While more research in humans is needed, this study underscores that the story of mitochondrial aging is not one of inevitable decline—but of structural adaptation that may shape health later in life.
Noone J. Respiratory Resilience as Form Fades: Skeletal Muscle Mitochondrial Adaptation in Aging. American Journal of Physiology. 2025 https://doi.org/10.1152/ajpendo.00369.2025
John Noone, PhD, is an Assistant Professor in Sport & Exercise Physiology at the Department of Physical Education and Sport Sciences in University of Limerick.
Email: john.noone@ul.ie
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