Healing Passion

06/10/2026

A fascinating new review in Aging Cell introduces the concept of Oxygenaging.
The authors argue that aging is not simply about “having less oxygen.” The deeper problem is that the body becomes less able to move oxygen efficiently from the lungs → blood → circulation → microvasculature → tissues → mitochondria.

That leads to a very important principle:
oxygen availability does not necessarily mean oxygen utility.

This is closely related to our recently published concept of bioenergetic impedance.
The same principle also applies to glucose and fatty acids. You can have plenty of fuel in the system, but if delivery, processing, mitochondrial utilization, or recovery is impaired, energetic output can still be constrained.

We therefore see Oxygenaging as one major layer of a broader picture:
oxygen-delivery impedance + carbon-substrate impedance + mitochondrial processing constraints → reduced energetic throughput → greater compensatory demand → slower recovery.

What is particularly interesting is that Luigi Ferrucci is among the authors. It suggests a broader convergence in geroscience toward studying not just what changes with age, but how well the organism can respond, adapt, and recover.

We discuss this connection in the new blog post:

Read more: https://wix.to/DknJoUs

A new review in Aging Cell proposes an intriguing way to think about aging. Rather than focusing only on mitochondrial dysfunction, vascular aging, or molecular hallmarks in isolation, Donega and colleagues follow oxygen through the entire physiological journey—from the atmosphere to the mitochond...

04/10/2026

A fascinating new Nature review by De Strooper and Karran proposes that Alzheimer’s disease progresses through a series of biological inflection points, rather than through one simple linear cascade.
One of the most interesting ideas is tissue permissiveness: the same amount of amyloid may be tolerated in one region of the brain but lead to Tau pathology and neuronal loss in another.
That raises a deeper question—why does the tissue become permissive?
In this blog, I explore a broader possibility: decades of environmental and physiological stress may generate repeated adaptation without complete recovery. Over time, this could create biological “backlog,” increase energetic strain, reduce the resources available for repair and proteostasis, and eventually impair the brain’s ability to process and clear amyloid.
A possible sequence is:
Exposome → incomplete recovery → hysteresis → bioenergetic impedance → proteostatic failure → amyloid accumulation → tissue permissiveness
This does not argue that amyloid is unimportant. Rather, amyloid may become both a consequence and an amplifier of declining cellular resilience.
Perhaps Alzheimer’s research needs to ask not only how to remove pathology, but how to preserve the capacity of the brain to recover before pathology becomes self-sustaining.
Read more: https://wix.to/HG65V0Q

When the Brain Can No Longer Keep Up For decades, Alzheimer’s disease has largely been told as a molecular story: amyloid-β accumulates, Tau pathology follows, neurons degenerate, and cognition declines.A new Nature review by Bart De Strooper and Eric Karran proposes a more dynamic picture. Rathe...

02/10/2026

A new study in Science describes how the mitochondrial transporter SLC25A34 helps brown fat coordinate its metabolism with the body clock, diet, and environmental temperature.
But the most interesting part may be the broader principle it reveals.
Metabolism depends on continuous flow.
Brown fat does not simply burn fat. It simultaneously synthesizes and breaks down lipid, while carbon metabolites such as oxaloacetate cycle between the cytosol and mitochondria.
These apparently “futile” cycles actually help maintain metabolic flexibility and thermogenic output.
If one transport step becomes constrained, however, substrates can accumulate on one side while becoming relatively deficient on the other. The system begins to reroute carbon, oxidative throughput falls, and congestion develops.
This provides a useful mechanistic example for our broader concept of bioenergetic impedance—the idea that biological energy production can become progressively constrained when metabolic flow and recovery cannot keep pace with demand.
Sometimes metabolic dysfunction may not begin because there is too little fuel.
It may begin because the system can no longer move fuel efficiently.
I explore the study and this broader interpretation in the new blog:
Metabolism Is a Flow Problem: What a New Mitochondrial Transporter Reveals About Cycling, Congestion, and Bioenergetic Impedance.

Read more: https://wix.to/JBecDBS

What a New Mitochondrial Transporter Reveals About Cycling, Congestion, and Bioenergetic ImpedanceWe often talk about metabolism as if it were a collection of separate pathways: glucose is burned, fat is stored, fat is oxidized, mitochondria make ATP.But metabolism is not a set of isolated reactions...

30/09/2026

Our body is always adapting. But can it still recover?

We're happy to share that our new scientific perspective has now been published in Frontiers in Network Physiology:

“Bioenergetic Impedance: A Network Physiology Framework for Stress Adaptation, Maladaptation, and Recovery.”

When we experience infection, lack of sleep, emotional stress, environmental exposures, undernutrition, or metabolic strain, the body does not simply “break down.”

It adapts.

It may redirect energy, change metabolism, activate stress responses, and temporarily reduce resources available to other functions.

That can be protective.

But if the pressure continues faster than the body can resolve it, those compensations may become increasingly difficult to reverse.

Recovery slows. Reserve declines. What began as adaptation may gradually become a persistent state.

We use the term bioenergetic impedance to describe this growing constraint on the body's ability to move and use energy efficiently relative to demand.

This leads to a question that increasingly guides our clinical and research thinking:

It is not only “Is this laboratory result normal?”

It is also “How hard is the body working to keep it normal—and can it still recover?”

Read the full paper:
https://doi.org/10.3389/fnetp.2026.1967461

25/09/2026

We usually think of fat cells as storage cells.

But adipocytes may also behave surprisingly like immune cells.

A new Cell Metabolism Perspective highlights evidence that adipocytes can detect pathogens, produce antimicrobial molecules, release inflammatory signals, alter metabolism during infection, communicate with immune cells, and even participate in antigen presentation.

This fits a broader idea we have been developing through our bioenergetic impedance framework.

Immune signaling does not necessarily begin with a macrophage or another classical immune cell.

A stressed adipocyte, epithelial cell, endothelial cell, fibroblast, or other tissue cell can sense that something is wrong and communicate that information to its neighbors.

In adipose tissue, we can imagine a progression like this:

increasing storage demand → declining spare capacity → “storage impedance” → compensatory remodeling and signaling → substrate spillover → propagation to other tissues.

At first, these responses may be adaptive.

The problem begins when the underlying constraint cannot be resolved.

The signals continue. Substrates continue to be rerouted. Neighboring tissues take on the burden. They may eventually develop their own constraints.

This leads to an interesting possibility:

chronic inflammation may sometimes represent persistent signaling from unresolved impedance.

Inflammation is then not necessarily the original problem. It may initially be part of the body's attempt to communicate, recruit resources, and restore function.

The transition to disease occurs when adaptation fails to return the system toward recovery.

Read the full discussion here: https://wix.to/YZD0YVM

We usually think of adipocytes as storage cells. They take up excess energy, package it into triglycerides, and release fuel when the body needs it. In obesity, the conventional story then runs in the opposite direction: adipocytes become too large, inflammation develops, insulin resistance follows,...

21/09/2026

We often imagine mitochondria as cellular furnaces: nutrients enter, carbon is completely oxidized, and ATP comes out.

But biology is much more dynamic.

Back in 2005, MacDonald and colleagues described how pancreatic β-cells reroute a large amount of glucose-derived carbon through anaplerosis and cataplerosis, producing and exporting TCA-cycle intermediates that support NADPH production, lipid metabolism, redox regulation, and insulin secretion.

Their work focused on these metabolites as signaling molecules.

Our forthcoming perspective on bioenergetic impedance offers another way to look at the same architecture.

Cells have finite oxidative throughput. When incoming substrate and energetic demand cannot simply be accommodated through one oxidative route, carbon may be redistributed into alternative pathways.

That rerouting may therefore be compensatory—not necessarily dysfunctional.

The important question becomes what happens next.

If the constraint resolves and the system recovers, the response may be adaptive.

If compensation has to remain active because recovery is incomplete, the same pathways may gradually become persistent and contribute to loss of flexibility.

This may be particularly relevant to aging, where the problem may not simply be that stress occurs, but that resolution becomes progressively more difficult.

Read the full article: https://wix.to/xYYnbqG

More than 20 years ago, Michael MacDonald and colleagues published a perspective that challenged a simple view of mitochondrial metabolism in pancreatic β-cells.The conventional story was straightforward: glucose enters the cell, mitochondria oxidize it, ATP rises, ATP-sensitive potassium channels ...

16/09/2026

We often talk about chronic inflammation as something that needs to be suppressed.

But inflammation itself is not necessarily the problem.

The real issue may be when the biological response cannot finish and resolve.

A recent review on inflammaging describes how mitochondrial dysfunction, cellular senescence, impaired immune surveillance, and chronic inflammation can reinforce one another during aging.

Our bioenergetic impedance perspective adds another way to look at this.

A damaged cell may first try to adapt and recover. If recovery becomes unsafe or impossible, it can enter senescence—stopping proliferation, which helps protect against tumor progression.

But the cell does not simply shut down.

It releases inflammatory signals—the SASP—to help stabilize its arrest, alert neighboring cells, and recruit the immune system for clearance.

That signaling is energetically costly. Yet biologically it makes sense: the priority has shifted from growth and recovery to containment and removal.

If the immune system clears the cell, resolution can still occur.

If clearance fails, however, those signals persist.

Persistent senescence → chronic inflammation → greater mitochondrial and tissue stress → poorer recovery → more senescence.

This may be one route through which several “hallmarks of aging” become locked together.

Read the full article: https://wix.to/yLTXaZU

Inflammation is often described as something that should be reduced. But biologically, inflammation is not inherently pathological. It is part of how the body responds to infection, injury, metabolic disturbance, and other forms of stress.The more important question may be:Can the inflammatory respo...

14/09/2026

We usually think of exercise and sleep as two separate healthy behaviors.

A new review suggests they may actually be connected by the same molecule: lactate.

Exercise produces a large lactate signal. Lactate can travel between tissues and into the brain, where it serves not only as fuel but also as a metabolic signal.

During slow-wave sleep, lactate metabolism may then help support memory replay, synaptic remodeling, and other energy-demanding restorative processes.

From our bioenergetic impedance perspective, this suggests an even broader cycle.

Exercise creates a temporary increase in energy demand. When glycolytic input exceeds immediate oxidative capacity, converting pyruvate into lactate helps maintain glycolysis and redistributes substrate.

After the challenge ends, recovery provides time for that substrate to be reused:

lactate → pyruvate → mitochondrial oxidation → ATP

That ATP can then support the work of restoration and memory consolidation during sleep.

So perhaps the important question is not whether lactate is “good” or “bad.”

The important question is whether the body can move through the whole sequence:

stress → adaptation → recovery.

Our perspective on this broader idea of bioenergetic impedance has now been accepted and is under production at Frontiers in Network Physiology.

The new blog explores how the Lactate Nexus may fit into that framework.

Read more: https://wix.to/wYWrLeI

For decades, lactate was treated mainly as a waste product of strenuous exercise. That view has changed dramatically. Lactate is now understood as an energy substrate, a signaling molecule, a regulator of blood flow and inflammation, and potentially even an epigenetic messenger.A new 2026 review by....

11/09/2026

We often think of aging as the gradual accumulation of damage.

But what if another part of the story is that our biology becomes progressively less able to finish its response to stress and recover?

A fascinating new Cell Metabolism review from Lambertucci, Castinetti, Martins, López-Otín, and Kroemer explores chronic glucocorticoid signaling from this perspective.

Cortisol is not inherently harmful. During acute stress, it helps mobilize energy, control inflammation, and prioritize survival.

The problem is when the adaptive response does not end.

Persistent glucocorticoid signaling can interfere with autophagy, mitochondrial maintenance, metabolism, tissue repair, and immune regulation. The authors also highlight the GC–ACBP/DBI pathway, which may connect prolonged stress signaling to changes in appetite, fat storage, insulin resistance, and immune function.

This suggests a useful way of thinking:

Respond → Adapt → Recover

Healthy physiology requires all three. Chronic disease may emerge when adaptation persists and recovery remains incomplete.

Maybe one of the important questions in aging is therefore not simply:

“How much damage has accumulated?”

but:

“How well can the system still recover?”

Read more: https://wix.to/QvU8JJ2

For decades, aging research has largely focused on what goes wrong with time: DNA damage accumulates, mitochondria become less efficient, proteins lose quality control, inflammation becomes persistent, stem cells lose regenerative capacity, and senescent cells accumulate.The hallmarks of aging frame...

10/09/2026

Stress is not always harmful. Much of the stress response is actually designed to protect us by temporarily changing how resources are used.

Recent research on ER stress and the integrated stress response shows how cells slow expensive activities such as protein synthesis, redirect resources toward survival and repair, and communicate with mitochondrial and immune pathways.

When the challenge resolves, this adaptation can switch off.

But if recovery remains incomplete, the same protective mechanisms may become persistent—contributing to inflammation, senescence, tissue dysfunction, and declining resilience.

In our new blog, we connect this cellular biology with the idea of bioenergetic impedance: when energetic demand increasingly exceeds the capacity to perform biological work and recover.

The key distinction may be:

temporary resource triage supports resilience; persistent resource triage can become maladaptation.
Read the full article: https://wix.to/FaiKjav

Stress is not automatically harmful. In fact, much of biology depends on the ability to detect a challenge, temporarily redirect resources, and then return toward normal function.The problem begins when that return never fully happens.Two recent reviews—one on the integrated stress response (ISR) ...