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Lack of Evidence for Gene-Level Convergence Linked to Evolutionary Shifts in Torpor Among Placental Mammals.

Torpor is a key survival strategy that many avian and mammalian lineages evolved in response to challenging environmental conditions. Whether the independent evolution of torpor in different lineages involved changes in the same genes remains poorly understood. Here, we performed comparative screens across 190 placental mammal genomes to comprehensively examine associations between loss, positive selection, and evolutionary rate shifts in individual protein-coding genes and evolutionary shifts in torpor use. We find that gene-torpor associations are highly clade-specific, with no gene being able to explain the majority of torpor shifts across the phylogeny of placental mammals. In contrast, there is more evidence, albeit still limited, for evolutionary convergence at the pathway level. Our results suggest that torpor emerged through several genetic routes in placental mammals, which likely explains the vast diversity of torpor use patterns that can be observed among torpor-capable species today.

Animals

Using Organoids to Unlock the Potential of Human Torpor for Spaceflight.

PURPOSE OF REVIEW: This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. RECENT FINDINGS: On future deep space missions such as NASA's planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement - all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. SUMMARY: This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.

Astronaut Health

Daily torpor in the absence of the suprachiasmatic nucleus in Siberian hamsters.

Siberian hamsters express torpor spontaneously after several weeks of exposure to short days. In long days, torpor is expressed only when food intake is restricted. Hamsters maintained in a long photoperiod (16 h light/day) at 15 degrees C expressed daily torpor during food restriction both before and after bilateral ablation of the suprachiasmatic nucleus (SCN). Hamsters housed in short days (8 h light/day, ambient temperature 15 degrees C) and fed ad libitum displayed torpor before, but not after, ablation of the SCN (SCNX). Torpor was reinstated in all short-day SCNX hamsters during postoperative food restriction and persisted in several animals even after ad libitum feeding was reinstated. Torpor was entrained to the light-dark cycle in both long- and short-day hamsters preoperatively but appeared to occur in a temporally random fashion in SCNX animals. SCNX hamsters, unlike control animals, displayed multiple torpor bouts per 24 h. The SCN is not essential for the expression of torpor but plays a crucial role in its temporal organization.

Animals

Metabolic, respiratory and haematological adjustments of the little pocket mouse to circadian torpor cycles.

Metabolic, respiratory and haematological parameters were investigated for the Little Pocket mouse during circadian torpor cycles. The rate of O2 consumption decreased from 7.04 to 0.05 ml O2.g-1.hr-1, with a corresponding decrease in respiratory minute volume from 49.4 to 0.9 ml.min-1 during torpor at an ambient temperature of 10 C. No changes in haemoglobin concentration (19.7 g/100 ml), haematocrit (54%), red blood corpuscle count (12.4 10(6)/microliter), mean corpuscular volume (43.6 micrometer3), mean corpuscular haemoglobin content (16.2 pg), mean corpuscular haemoglobin concentration (37.4%) and [2,3-DPG] (9.6 mumol/g Hb) were observed during torpor cycles. The half saturation tension of P. longimembris haemoglobin was 41 mm Hg (37 C, pH = 7.28) and 19.7 mm Hg (10 degrees C, pH = 7.51). The effect of temperature on P50 was deltalog P50/ C = +0.0106 (pH = 7.4). Venous blood parameters were: euthermic mice (37 C); PCO2 = 36.8 mm Hg, PO2 = 49.5 mm Hg, pH = 7.28, [HCO-3] = 17.3 mmol/l; torpid mice (10 C); PCO2 = 14.6, PO2 = 35.7 pH = 7.51, [HCO-3] = 18.8. These data indicate a new, relatively acidotic acid-base status during torpor, characterised by a higher H+/ OH- ratio. The respiratory sensitivity to inspired CO2 of pocket mice was, despite their being semi-fossorial, typical of other mammals. High concentrations of CO2 did not induce, or facilitate, entry into torpor.

Acid-Base Equilibrium

Sleep and estivation (shallow torpor): continuous processes of energy conservation.

Estivation (shallow torpor) in the round-tailed ground squirrel (Citellus tereticaudus) is entered through electrophysiologically defined states of sleep. Rapid-eye-movement sleep diminishes as body temperature falls in such a way that, at a body temperature of 26 degrees to 28 degrees C, torpor is characterized by almost continuous slow-wave sleep isomorphic with that observed at euthermic body temperatures.

Animals

Body temperature and metabolic rate during natural hypothermia in endotherms.

During daily torpor and hibernation metabolic rate is reduced to a fraction of the euthermic metabolic rate. This reduction is commonly explained by temperature effects on biochemical reactions, as described by Q10 effects or Arrhenius plots. This study shows that the degree of metabolic suppression during hypothermia can alternatively be explained by active downregulation of metabolic rate and thermoregulatory control of heat production. Heat regulation is fully adequate to predict changes in metabolic rate, and Q10 effects are not required to explain the reduction of energy requirements during hibernation and torpor.

Animals

Integrated transcriptomic analysis of mRNA and miRNA in Brown adipose tissue of the greater horseshoe bats during hibernation.

Hibernation enables animals survive harsh environments by conserving energy through reduced metabolism and body temperature. Brown adipose tissue (BAT) plays a critical role in non-shivering thermogenesis, crucial for warming up during arousal phase. The greater horseshoe bats (Rhinolophus nippon) are typical hibernators and non-shivering thermogenesis in BAT tissue may persist throughout the arousal process in bats. This study examines gene expression and regulatory changes in BAT of these bats across active, hibernation, and arousal phases using transcriptome and miRNA sequencing. A total of 2721 differentially expressed mRNAs and 268 differentially expressed miRNAs were identified. The results reveal that the BAT transcriptome undergoes state-dependent remodeling throughout the hibernation process. The most pronounced divergence occurs between the active phase and torpor, involving cell cycle arrest, immunosuppression, thermogenic signal desensitization, and upregulation of lipid metabolism and autophagy pathways, reflecting the coordinated adaptation of energy conservation and thermogenic reserve. In contrast, transcriptional alterations between torpor and arousal are extremely limited, indicating that torpid BAT is already pre-primed for thermogenesis and requires only modest transcriptional adjustments to activate heat production. Notably, although body temperature recovers to active-phase levels during arousal, the molecular signature of BAT remains highly similar to that of the torpid state. Furthermore, the core thermogenic gene UCP1 showed no significant expression differences across the three groups. In conclusion, this study systematically delineates the miRNA-mRNA regulatory landscape of bat BAT across the hibernation process, and deepens our understanding of the thermoregulatory mechanisms underlying mammalian hibernation.

BAT

Hibernation and circannual rhythms of food consumption in marmots and ground squirrels.

In order to understand better the evolution and adaptive value of hibernation, ecological aspects and experimental studies of closely related hibernators, the Marmotini, are examined. The central hypothesis is that annual changes in the environment integrate three or, perhaps, four physiological processes: torpor, reporduction, consumption of food, and metabolism. Reproduction occurs promptly after emergence from hibernation. For most species, the breeding season is very short. Although the experimental data are rather meager, no variation in external factors has consistently altered the season of reproduction. Consumption of food and change in weight increases until July or September and then decreases. The large members of the Marmotini store their energy as fat, but small species store their energy as seeds and nuts. Experiments to test the hypothesis that some aspect of the supply, such as fat content, might vary seasonally have produced negative results. Complex experiments on the length of the photoperiod on woodchucks and several species of ground squirrels failed to alter the annual cycle of consumption of food. Animals kept in constant conditions showed a cycle of about 11 months, but woodchucks sent tto Australia changed their cycle in two years to match the seasons of the southern hemisphere. Experiments with temperature and torpor and castration did not alter the annual did not alter the rhythm...

Adipose Tissue

[Lethargic hypothermia induced by a protein free diet in a hibernating rodent, the dormouse (Eliomys quercinus L.)].

In garden dormouse protein deficiency leads to reversible hypothermic torpor, comparable with that provoked by starvation or occuring naturally during hibernation, whether the diet consists wholly of apples or of synthetic protein-free food. Torpor induced by protein deficiency occurs even though the energy requirements of the animal are amply satisfied. These phases of lethargy occur after a certain delay and with a variable frequency, both of which vary with the ambient temperature.

Animals

Reproduction of the canyon bat, Pipistrellus hesperus, in southwestern United States.

The reproductive biology of the bat Pipistrellus hesperus was investigated histologically using animals obtained from nature at monthly intervals throughout the year. The female shows proestrous morphological changes in late summer and autumn, which continue until early spring. Insemination is probably effected several times during proestrous, since both sexes are intermittently active throughout this period (August--April). Permanent arousal from torpor and return to normal metabolism in the spring results in ovulation. Both ovaries are functional and both uterine horns may be utilized. P. hesperus is monestrous; two young per bat is usual. The male spermatogenic cycle is initiated in late June and the first sperm are available for ejaculation in September. Some sperm remain in the seminiferous tubules until early March. The epididymides also serve in sperm storage with the caput emptied by late February and the cauda in April. Leydig cells are largely nonsecretory from March through July, a few are secretory in August and most are secretory in September and October. Active cells gradually decline in number until few are secretory in late March. Accessory sex glands are functionally cyclic: they are small from April through August, hypertrophy in September, and gradually involute to the resting stage through March, to achieve total involution in April. The penis, similar in structure to that of other vespertilionids, is thought specialized to insure effective insemination.

Animals

The hypothalamo-hypophysial system in the ground squirrel, Citellus erythrogenys Brandt. II. Seasonal changes in the classical neurosecretory system of a hibernator.

Monthly observations of the "Gomori-positive" hypothalamo-hypophysial neurosecretory system (HHNS) of the ground squirrel, Citellus erythrogenys Brandt, were carried out light microscopically using several quantitative methods. From the beginning of hibernation, formation of neurosecretory material (NSM) in the neurosecretory cells (NSC) progressively decreases and release of neurohormones from the HHNS is almost fully inhibited. A maximal accumulation of NSM in the perikarya of the NSC and in the posterior pituitary (PP) is found in December. By this time the volume of the cell nuclei and nucleoli is at a minimum. Signs of activation of the HHNS appear and become more conspicuous as the time of arousal from torpor approaches. The amount of NSM in the NSC and the PP decreases simultaneously with the increase in volume of the NSC. Hyperemia and activation of glial elements is visible throughout the HHNS. The morphological signs of activation reach their peak in March. After reproduction is completed (April to beginning of May), the NSC and the PP are almost devoid of NSM. Beginning with June and during the summer and autumn months a progressive accumulation of NSM in the NSC and the PP parallels gradual diminution in the volume of the NSC structures and the glial cells. Mechanisms and effector pathways by which the HHNS influences seasonal adaptation of the organism and reproduction are discussed.

Animals

Hibernation and body weight in dormice: a new type of endogenous cycle.

Under conditions unfavorable to hibernateion (22 degrees C), the body-weight cycles of dormice are only a few weeks long, but under conditions in which dormice hibernate (5 degrees C), the cycles can last many months; the more the animals hibernate, the longer are the cycles. Such cycles contrast with the relative independence from torpor of the period of circannual cycles in other hibernating rodents and with the temperature compensation of circannual and circadian cycles in general.

Animals