Physiology’s New Normal Includes Plasticity, Intermittency and Stochastic Control

A broad review of physiological regulation argues that the familiar image of homeostasis as the maintenance of narrow, stable internal conditions is only one part of life’s normal operating strategy. Across animals, the authors identify cases in which temperature, metabolism, breathing, digestion, hormone secretion, sleep, renal blood flow and immune-cell production vary widely, cycle periodically or fluctuate unpredictably. These patterns are often adaptive rather than evidence of disease or failed control, although the review cautions that no experimental criteria yet exist for consistently separating adaptive intermittency from genuine loss of regulation.

Classical homeostasis, formalized by Walter Cannon and rooted in Claude Bernard’s idea of the internal environment, describes coordinated mechanisms that hold variables such as blood pH, temperature and tissue oxygenation within relatively narrow limits. Its many conceptual extensions—including allostasis, adaptive homeostasis, rheostasis and temporal homeostasis—allow internal conditions or reference ranges to shift. The review does not propose yet another label. Instead, it argues that the existing vocabulary remains too restrictive when physiological regulation includes wide operating ranges, stochastic swings, temporary pauses and periodic processes that alternate between controlled and apparently unregulated states.

Part of the problem is the dominance of mammalian research in physiology. The authors report that an informal June 2026 PubMed search found nearly 80% of roughly 440,000 publications containing the word “homeostasis” were partially or exclusively based on mammals. This focus has reinforced an image of narrow physiological limits, particularly in humans, where substantial excursions in variables such as body temperature are often interpreted as pathological. Invertebrate physiologists, by contrast, commonly encounter extensive normal variation and are more inclined to regard homeostasis as one possible regulatory strategy rather than a universal definition of life.

Environmental conditions can produce some of the most dramatic departures from canonical stability. Many mammals display adaptive heterothermy, allowing body temperature to vary with weather, food availability or prolonged thermal stress. Hibernation, winter sleep, torpor and estivation can involve still larger shifts, produced through interactions among endogenous clocks, metabolism and the environment. Such animals do not simply lose control: during moderate conditions they may regulate temperature closely, while during dormancy they defend selected variables such as fluid balance and blood clotting while allowing others to vary. The result is selective homeostasis, in which tight control of one component coexists with loose or intermittent control of another.

Breathing offers another striking example. Diving mammals and birds routinely experience apneas lasting minutes or hours, while intermittent ventilation is also natural for aquatic amphibians, many air-breathing fishes and some reptiles. Arterial oxygen can fall by more than 100 millimetres of mercury during exceptionally long dives by freshwater turtles, and captive dolphins have shown carbon-dioxide increases from 54 to 84 millimetres of mercury with a concurrent blood-pH decline from 7.54 to 7.35 during prolonged apnea. These observations do not demonstrate the absence of respiratory homeostatic mechanisms; they indicate enhanced tolerance of large internal changes, plastic control that can suspend familiar chemical setpoints, or both.

Intermittent feeding exposes equally dramatic physiological reversals. Large snakes and boas may fast for weeks or months and then consume prey amounting to 20% to 100% of their body mass. During fasting, their metabolism falls sharply, and the heart, intestine, liver and kidneys can shrink by 50% to 80%, reducing the cost of maintaining tissues. After feeding, metabolism may rise 10-fold to 40-fold, the small intestine can double in mass within 48 hours, and digestive enzymes, nutrient transporters, blood flow, cardiac output and water demand all increase. The review describes this cycle as extreme, regulated plasticity rather than canonical steady state, with brief periods resembling conventional homeostasis amid prolonged deviations shaped by infrequent feeding.

Intrinsic rhythms and noisy oscillators also shape normal physiology. Metabolic rates can vary with time of day independently of body temperature: measured metabolic rhythms have been reported in dozens of Israeli lizard species, while epaulet sharks show nearly twofold diel variation. Tidal and lunar rhythms have also been documented, although the difficulty of isolating animals from every possible environmental timing cue limits certainty. In mammals, hormones including gonadotropin-releasing hormone, luteinizing hormone, growth hormone, insulin, glucagon, thyroid-stimulating hormone, glucocorticoids and parathyroid hormone are released in pulses. Irregular spacing and variable amplitude suggest that some endocrine systems behave like noisy or stochastic oscillators rather than perfectly deterministic pacemakers.

The same irregularity appears in several human and mammalian processes. Sleep includes cycles but also nonperiodic events such as K-complexes, sleep spindles and microarousals. Renal vascular control exhibits spontaneous periodic and irregular oscillations in blood flow, pressure and feedback activity, even though total kidney function remains regulated; fluctuations in humans can be associated with exercise, circadian timing, diet and body temperature. Gastric emptying proceeds through recognizable phases but remains irregular in duration and contraction strength, including within an individual receiving standardized meals. These findings show why overall averages can conceal important variation across time, tissues and individual units such as nephrons.

Immune regulation supplies a particularly instructive example of purposeful stochasticity. Intrinsic noise, discrete cellular events and fluctuating microenvironments can generate burst-like immune responses rather than continuous, precisely timed activity. Stochastic production of diverse T-cell subtypes may act as a bet-hedging strategy: compared with a highly polarized response focused on one pathogen, a varied cell population may provide moderate protection against that pathogen while preserving some protection against others. The resulting defense can be less variable across unpredictable infections, even if it is not maximally efficient against any single threat. Here, randomness is embedded within a regulated process rather than indicating absent control.

Some animals preserve effective function by allowing their internal chemistry to move. In blue crabs, hemolymph osmolality closely tracks environmental salinity from 35 parts per thousand down to about 27 parts per thousand, apparently conserving energy by reducing osmoregulatory work. In fresher water, the crabs partially defend their internal osmolality, yet adult animals can remain functional for days or weeks, although reproduction is impaired. This pattern resembles enantiostasis: constancy of function rather than constancy of the internal environment. Insects may achieve similar outcomes by correcting some changes in extracellular fluid volume, solute content and osmotic pressure while allowing compensation through other variables. The review also notes that hibernating mammals can actively regulate metabolism, fluid balance and clotting while displaying stochastic temperature flickers, showing that even a strongly homeostatic system can contain hidden irregular components.

The central implication is methodological. Future experiments could manipulate hormones, nerves or environmental conditions and then measure feedback gain, metabolic rate, abrupt versus graded transitions and cyclic off-and-on phases to test whether apparently unregulated variation is actively controlled. That distinction is crucial: normal biological variability should not automatically be pathologized, particularly because wide variation can arise from genetics, season, reproductive condition, feeding state, age or other intrinsic factors. The authors argue that natural selection may favor intermittent or stochastic regulation when maintaining every variable within a narrow range is energetically costly, but they present that explanation as a hypothesis rather than a demonstrated result. Their review does not discard homeostasis; it argues for a broader view in which stable regulation, shifting setpoints, rhythms, pauses and stochastic behavior coexist as parts of animal physiology.

Subject of Research: Comparative review of plastic, intermittent and stochastic physiological regulation across animals

Article Title: Beyond canonical homeostasis: Dynamic, plastic, and intermittently unregulated physiology as the norm

Article References: Burggren, W., & Wang, T. (2026). Beyond canonical homeostasis: Dynamic, plastic, and intermittently unregulated physiology as the norm. Physiological Reports, 14(20), Article e71150. https://doi.org/10.14814/phy2.71150

Image Credits: AI Generated

DOI: 10.14814/phy2.71150

Keywords: homeostasis, physiological regulation, allostasis, adaptive heterothermy, metabolic rhythms, endocrine pulsatility, immune stochasticity, renal blood flow, intermittent breathing, comparative physiology, Beyond, canonical