From cancer to Alzheimer’s: could a renewed focus on energy transform biomedicine?

## Summary
The ‘astounding’ rise of semaglutide — and what’s next for weight-loss drugs Discovering the molecular processes associated with this energy flow has led to fields of research dedicated to metabolism. Still, much of the biomedical research literature omits explicit considerations of energy dynamics in health and disease, focusing instead on genes, proteins and molecular mechanisms. Energy constraints In our view, developing a theoretical framework of ‘energy constraints’ is a promising way to learn more about the underpinnings of health and disease in a way that translates across species. Here are five examples. • What are the energy costs of this function or disease? • Which other processes are simultaneously competing for the finite energy budget? • Could this trait be driven by energy constraints or trade-offs? • How much energy do the side effects of this treatment cost? • What patient behaviours might compete with the energetic costs of healing?

## Article Content
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Energy flows through all living organisms constantly. Credit: Henrik Sorensen/Getty
Every biological process requires energy, from a neuron firing to a cell making proteins, and from digesting dinner to taking a stroll. Energy flows constantly through every part of a cell, in chemical, thermal, mechanical or electromagnetic form.
The ‘astounding’ rise of semaglutide — and what’s next for weight-loss drugs
Discovering the molecular processes associated with this energy flow has led to fields of research dedicated to metabolism. Still, much of the biomedical research literature omits explicit considerations of energy dynamics in health and disease, focusing instead on genes, proteins and molecular mechanisms.
In our view, more biomedical scientists should pay attention to energy. Why? Because a focus on molecules is not enough to help us to understand what underpins biological processes and diseases. Both a cadaver and a thinking, feeling, living person are made up of molecules, cells, tissues and organs — the fundamental distinguishing factor is energy flow.
Molecular pathways that control diverse aspects of biology vary between individuals and between species because they are underpinned by genetics. It is no surprise, then, that molecular mechanisms of disease found in mice, fruit flies, zebrafish and other model systems often fail to hold up when studied in humans.
By contrast, the behaviour of energy in living systems follows several first principles from physics that apply across species more generally.
Take the metabolic theory of ecology, which explains why cells in large mammals burn energy more slowly than do cells in smaller ones. Simply put, nutrient and oxygen supplies are limited by fundamental physical constraints
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. Oxygen-carrying blood cells, for instance, must be pumped through vascular tubes that face hydraulic resistance — it takes longer for blood cells to travel optimally through a larger body than through a smaller one.
Losing weight through better sleep
This general principle has been used to explain many physiological, ecological and evolutionary phenomena for which answers are not just written in genes
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. For example, it can explain why most large animals live longer and reproduce more slowly than do smaller ones.
To encourage debate, here we speculate on how making energy dynamics a central focus of biomedical studies might help researchers to unearth a fundamental layer of biological regulation that underlies health and goes awry in disease. Biologists should get into the habit of asking simple questions, such as ‘how much energy does this cost?’.
Energy constraints
In our view, developing a theoretical framework of ‘energy constraints’ is a promising way to learn more about the underpinnings of health and disease in a way that translates across species.
This framework
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–
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describes how organisms allocate their finite energy budgets to various cellular, physiological and behavioural processes. It rests on two facts, both of which have been accepted for decades.
First, every organism’s energy budget is limited
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— it’s impossible for eating ever more food to produce infinitely more energy. Scaling arguments based on physical constraints, such as hydraulics, tell us that rates of energy supply to an organism are already optimized. And data show that the ability of organisms to dissipate thermal energy could, under some conditions, be part of why living beings can’t increasingly speed up their metabolism
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.
Second, organisms require specific amounts of energy for each function and system that cannot be reduced easily. The brain might need 20% of the body’s total energy supply to keep functioning, digesting food might cost 10–15% and so on. The total energy cost of all body functions, each running at maximum capacity, would be greater than the overall energy budget.
Finite energy resources mean that the body cannot keep going without resting.
Credit: Kevin Liles/
Sports Illustrated
/Getty
Taking both points together, it follows that not all of the body’s systems can be ‘on’ at once. Organisms must continually divide finite energy resources between cellular functions, organs and behaviours. If an individual process needs more energy than usual, that energy has to be ‘stolen’ from other processes. Those decisions are called energy trade-offs.
Proponents of energy-constraint theories have begun to gather evidence that such a framework could explain a range of physiological phenomena
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. For instance, healthy young female athletes sometimes stop menstruating when their training regime becomes too intense. Studies suggest that the body’s finite energy budget might be allocated to performance in a trade-off with reproduction
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.
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Similarly, energy constraints might explain why a group of Shuar Amazonian children who were exposed to viral and parasitic pathogens throughout

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## Expert Analysis

### Merits
- Energy constraints In our view, developing a theoretical framework of ‘energy constraints’ is a promising way to learn more about the underpinnings of health and disease in a way that translates across species.
- But there are areas in which a wealth of expensive molecular investigations has yet to lead to effective treatments (including for Alzheimer’s disease , mental-health conditions and some cancer types), pointing to a need to consider other avenues, too.

### Areas for Consideration
N/A

### Implications
- In our view, more biomedical scientists should pay attention to energy.
- To encourage debate, here we speculate on how making energy dynamics a central focus of biomedical studies might help researchers to unearth a fundamental layer of biological regulation that underlies health and goes awry in disease.
- Biologists should get into the habit of asking simple questions, such as ‘how much energy does this cost?’.
- And data show that the ability of organisms to dissipate thermal energy could, under some conditions, be part of why living beings can’t increasingly speed up their metabolism 4 .

### Expert Commentary
This article covers energy, article, google topics. Notable strengths include discussion of energy. Readability: Flesch-Kincaid grade 0.0. Word count: 1856.