Aging Metabolism: When Energy Flow Slows but Never Stops

A new paper in Cell Metabolism (Jankowski et al., 2025) has quietly rewritten one of aging biology’s assumptions. Researchers from Princeton used state-of-the-art metabolomics and isotope tracing to follow how nutrients actually flow through the bodies of aged mice.

The surprise?

Even though hundreds of metabolite levels changed with age, the major energy fluxes—the rates at which glucose, fats, and amino acids cycle through the bloodstream—remained almost perfectly preserved. Only one metabolite, glutamine, showed a notable increase in flux, about 30 percent higher in old mice.

At first glance, this looks like good news: the metabolic “pipes” of energy seem to stay open. But dig a little deeper, and it tells a subtler story about how the body copes with waning mitochondrial efficiency.

When the Power Grid Falters

The mitochondria—the cell’s power plants—lose some of their spark with age. Enzymes in the electron-transport chain (ETC) become less efficient at turning fuel into ATP, and small leaks of electrons generate oxidative stress.

To keep energy flowing, cells reroute their biochemistry. One classic adaptation is to rely more on glutaminolysis—burning glutamine instead of glucose or fat. Glutamine can be converted directly into α-ketoglutarate, feeding the TCA cycle downstream of the ETC’s most sensitive entry points. In simple terms, it’s like using a side road when the main highway is congested.

A Costly Workaround

This compensatory pathway helps maintain ATP output and redox balance, but it comes with a price. Glutamine is drawn largely from skeletal muscle, the body’s biggest amino-acid reservoir.

Over years, chronic reliance on glutaminolysis may gradually erode muscle protein stores, contributing to sarcopenia—the quiet loss of muscle mass and strength that shadows aging. Energy is preserved, but structure slowly declines.

The Bigger Picture: Adaptation, Not Failure

Seen through the lens of the Exposure-Related Malnutrition (ERM) framework, these findings highlight how the body prioritizes survival: maintaining energy flow even when efficiency drops. Aging, then, isn’t simply “low energy,” but a state of bioenergetic adaptation under constraint—steady flux sustained by shifting substrates and sacrificing long-term reserves.

In short, the study reminds us that the aged body is not metabolically idle; it’s working hard to keep the lights on despite a fading power grid.

Supporting mitochondrial health—through movement, rhythmic feeding, micronutrient sufficiency, and recovery—may help reduce the need for this costly detour and preserve both energy and muscle for the long run.

Jankowski, C. S. R., Samarah, L. Z., MacArthur, M. R., Mitchell, S. J., Weilandt, D. R., Hunter, C. J., Zeng, X., McReynolds, M. R., & Rabinowitz, J. D. (2025). Aged mice exhibit widespread metabolic changes but preserved major fluxes. Cell Metabolism, 37(11), 2280–2294. https://doi.org/10.1016/j.cmet.2025.09.009