CO2 levels over the past 500 million years. Foster et al – Descent into the icehouse.

OBJECTIVE—The goals of this study were to determine whether improvements in metabolic control can ameliorate the cognitive dysfunction associated with type 2 diabetes and evaluate the possibility that such improvements are mediated by changes in circulating insulin or insulin resistance.

RESEARCH DESIGN AND METHODS—This randomized double-blind trial enrolled 145 subjects at 18 centers in the U.S. Older adults with type 2 diabetes receiving metformin monotherapy received add-on therapy with either rosiglitazone, a thiazolidinedione insulin sensitizer, or glyburide. Cognitive function was assessed at baseline and week 24 using the Digit Symbol Substitution Test, the Rey Auditory Verbal Learning Test, and the Cambridge Neuropsychological Test Automated Battery.

RESULTS—Pretreatment fasting plasma glucose (FPG) in both groups was similar, and after 24 weeks both treatment groups showed similar significant reductions in FPG (2.1–2.3 mmol/l). Working memory improved with both rosiglitazone (P < 0.001) and glyburide (P = 0.017). Improvement (25–31% reduction in errors) was most evident on the Paired Associates Learning Test and was significantly correlated (r = 0.30) with improved glycemic control as measured by FPG.

CONCLUSIONS—Similar and statistically significant cognitive improvement was observed with both rosiglitazone and glyburide therapy, and the magnitude of this effect was correlated with the degree to which FPG improved. These results suggest that a cognitive benefit is achievable with pharmacological interventions targeting glycemic control.
https://diabetesjournals.org/care/article/29/2/345/26200/Improving-Metabolic-Control-Leads-to-Better

Would this explain that animals in barren areas such as polar bears and African elephants tended to be larger than their forest counterparts, due to lack of allergens in the air?

Histological and biochemical study of the superficial abdominal fascia and its implication in obesity
Abstract
The advancement of liposculpturing and fascial flaps in reconstructive surgery has renewed interest in the superficial fascia of abdomen. Its histological and biochemical composition may play a vital role in maintaining strength and elasticity of the fascia. Hence, study of abdominal fascia for the elastic, collagen, and hydroxyproline contents is desirable to understand asymmetrical bulges and skin folds and in improving surgical treatment of obesity. Samples of superficial fascia were collected from of upper and lower abdomen from 21 fresh cadavers (15 males and 6 females). Samples were stained using Verhoeff–Van Gieson stain. Digital images of superficial fascia were analyzed using TissueQuant software. The samples were also subjected to hydroxyproline estimation. The superficial fascia was formed by loosely packed collagen fibers mixed with abundant elastic fibers and adipose tissue. Elastic contents and collagen contents of superficial fascia were significantly more in the upper abdomen than that in the lower abdomen in males. Hydroxyproline content of superficial fascia of upper abdomen was significantly more than that of lower abdomen in both males and females. The elastic, collagen and hydroxyproline contents of superficial fascia of upper abdomen were higher compared to the lower abdomen. This may be a reason for asymmetric bulging over abdomen and more sagging fold of skin in the lower abdomen than in the upper abdomen. This study may therefore be helpful in finding new ways to manage obesity and other body contour deformities.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5052227/

Muscle Pain: It May Actually Be Your Fascia
Ways to Relieve Fascia Pain
There are various strategies that work to loosen up painful knots, such as:

Heat therapy: Apply a heating pad to the affected area or take a warm shower or bath.
Yoga therapy: See a highly trained yoga therapist to get a regimen of yoga poses targeted to treat your area of pain. (Yoga therapy works in the same manner as physical therapy — the therapist creates a routine and you practice it at home between visits.)
Foam rolling: Try a foam roller, a cylinder of hard foam that you roll your body over to release tension. It’s a form of self-massage. You can also do this with a lacrosse ball.
Massage therapy: Schedule multiple therapeutic massage sessions with an experienced therapist who can find and apply pressure to release knots.
Acupuncture: The insertion of acupuncture needles into trigger points can cause tense tissue fibers to relax.
https://www.hopkinsmedicine.org/health/wellness-and-prevention/muscle-pain-it-may-actually-be-your-fascia

Yoga Poses for Myofascial Release | 5 Poses to Try
https://www.acefitness.org/resources/everyone/blog/5667/yoga-poses-for-myofascial-release-5-poses-to-try/

Influence of gravity on cardiovascular reflexes from skeletal muscle receptors
Abstract
Skeletal muscles are important reflexogenic areas of the cardiovascular system. The afferent pathways of the reflex loops involve slow-conducting group III and group IV fibers that are excited by mechanical and chemical events in the muscle. The present paper reviews a series of experiments dealing with the question of whether those afferents are also influenced by gravitational forces. The results of these studies suggest the following answers: 1) gravitational forces can modulate cardiovascular reflexes from exercising skeletal muscles. 2) This effect is primarily due to changes in the interstitial fluid volume rather than to a direct mechanical influence, venous pressure, or venous volume. 3) The amplitudes of heart rate and blood pressure responses during exercise are inversely related to the local interstitial volume. Measurements during post-exercise circulatory arrest indicate that this sensitivity is mainly mediated by muscle chemoreceptors. These receptors, which also contribute to the spinal control of movement, generally appear to be sensitized by regional fluid losses and desensitized by overhydration of their environment.
https://pubmed.ncbi.nlm.nih.gov/8897399/

Muscle Forces or Gravity: What Predominates Mechanical Loading on Bone?
However, even low-impact gravitational loading may have beneficial skeletal effects, because standing for 40 h·wk−1 or more (which presumably included time spent walking) was associated with a 34% to 46% lower risk of hip fracture (9).
...
several lines of research suggest that physical activities that involve impact forces, and therefore generate both gravitation and muscle loading, are most likely to have beneficial effects on bone metabolism and reduce fracture risk.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3037021/

Gravitational Effects on Human Physiology
Abstract
Physical working capacity decreases with age and also in microgravity. Regardless of age, increased physical activity can always improve the physical adaptability of the body, although the mechanisms of this adaptability are unknown. Physical exercise produces various mechanical stimuli in the body, and these stimuli may be essential for cell survival in organisms. The cytoskeleton plays an important role in maintaining cell shape and tension development, and in various molecular and/or cellular organelles involved in cellular trafficking. Both intra and extracellular stimuli send signals through the cytoskeleton to the nucleus and modulate gene expression via an intrinsic property, namely the "dynamic instability" of cytoskeletal proteins. αB-crystallin is an important chaperone for cytoskeletal proteins in muscle cells. Decreases in the levels of αB-crystallin are specifically associated with a marked decrease in muscle mass (atrophy) in a rat hindlimb suspension model that mimics muscle and bone atrophy that occurs in space and increases with passive stretch. Moreover, immunofluorescence data show complete co-localization of αB-crystallin and the tubulin/microtubule system in myoblast cells. This association was further confirmed in biochemical experiments carried out in vitro showing that αB-crystallin acts as a chaperone for heat-denatured tubulin and prevents microtubule disassembly induced by calcium. Physical activity induces the constitutive expression of αB-crystallin, which helps to maintain the homeostasis of cytoskeleton dynamics in response to gravitational forces. This relationship between chaperone expression levels and regulation of cytoskeletal dynamics observed in slow anti-gravitational muscles as well as in mammalian striated muscles, such as those in the heart, diaphragm and tongue, may have been especially essential for human evolution in particular. Elucidation of the intrinsic properties of the tubulin/microtubule and chaperone αB-crystallin protein complex systems is expected to provide valuable information for high-pressure bioscience and gravity health science.
https://pubmed.ncbi.nlm.nih.gov/26174402/

Perspective on the Impact of Weightlessness on Calcium and Bone Metabolism
Abstract
As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%–2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity’s effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts’ bone health.
https://www.sciencedirect.com/science/article/pii/S8756328298000143

Does gravitational pressure of blood hinder flow to the brain of the giraffe?
The giraffe has a high aortic pressure. This is not for driving the blood to its head but is for minimizing the gravitational drop of intravascular pressure and collapse of the vessels. The cerebral circulation is protected by the cerebrospinal fluid which undergoes parallel changes in pressure with posture. Other vessels in the head are less protected by connective tissue, surrounding muscles and other structures.
https://www.sciencedirect.com/science/article/abs/pii/0300962986905621

The roles of exercise in bone remodeling and in prevention and treatment of osteoporosis
Conclusion
Exercise increases bone mineral density, bone mass, bone strength, and bone mechanical properties. It seems to directly or indirectly act on almost all the bone cell types and affect many aspects of bone remodeling.
https://www.sciencedirect.com/science/article/abs/pii/S007961071500228X

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression
Conclusions: The present study is the first to show that r-irisin positively regulates osteoblast differentiation under simulated microgravity through increasing β-catenin expression, which may reveal a novel mechanism, and it provides a prevention strategy for bone loss and muscle atrophy induced by microgravity.
https://www.mdpi.com/1422-0067/21/4/1259

Summary
Gastric emptying is increased during running (50%–70% maximal aerobic uptake, as compared to rest. Whether this increase varies as a function of mode (i. e. walking vs running) and intensity of treadmill exercise is unknown. To examine the gastric emptying characteristics of water during treadmill exercise performed over a wide range of intensities relative to resting conditions, 10 men ingested 400 ml of water prior to each of six 15 min exercise bouts or 15 min of seated rest. Three bouts of walking exercise (1.57 m · s−1) were performed at increasing grades eliciting ∼28%, 41% or 56% of. On a seperate day, three bouts of running (2.68 ms−1) exercise were performed at grades eliciting ∼57%, 65% or 75% of. Gastric emptying was increased during treadmill exercise at all intensities excluding 75% as compared to rest. Gastric emptying was similar for all intensities during walking and at 57% and 65% during running. However, running at 74% decreased the volume of original drink emptied as compared to all lower exercise intensities. Stomach secretions were markedly less during running as compared to walking and rest. These data demonstrate that gastric emptying is similarly increased during both moderate intensity (∼8%–65%) walking or running exercise as compared to resting conditions. However, gastric emptying decreases during high intensity exercise. Increases in gastric emptying during moderate intensity treadmill exercise may be related to increases in intragastric pressure brought about by contractile activity of the abdominal muscles.
https://link.springer.com/article/10.1007/BF00643522

Three 15-min Bouts of Moderate Postmeal Walking Significantly Improves 24-h Glycemic Control in Older People at Risk for Impaired Glucose Tolerance
RESULTS
Both sustained morning walking (127 ± 23 vs. 118 ± 14 mg dL−1) and postmeal walking (129 ± 24 vs. 116 ± 13 mg dL−1) significantly improved 24-h glycemic control relative to the control day (P < 0.05). Moreover, postmeal walking was significantly (P < 0.01) more effective than 45 min of sustained morning or afternoon walking in lowering 3-h postdinner glucose between the control and experimental day.
https://diabetesjournals.org/care/article/36/10/3262/30770/Three-15-min-Bouts-of-Moderate-Postmeal-Walking

The role of melatonin in bone regeneration: A review of involved signaling pathways
Abstract
Increasing bone resorption followed by decreasing bone mineralization are hallmarks of bone degeneration, which mostly occurs in the elderly population and post-menopausal women. The use of mesenchymal stem cells (MSCs) has raised many promises in the field of bone regeneration due to their high osteoblastic differentiation capacity and easy availability from abundant sources. A variety of compounds, including growth factors, cytokines, and other internal factors, have been combined with MSCs to increase their osteoblastic differentiation capacity. One of these factors is melatonin, whose possible regulatory role in bone metabolism and formation has recently been suggested by many studies. Melatonin also is a potential signaling molecule and can affect many of the signaling pathways involved in MSCs osteoblastic differentiation, such as activation of PI3K/AKT, BMP/Smad, MAPK, NFkB, Nrf2/HO-1, Wnt, SIRT/SOD, PERK/ATF4. Furthermore, melatonin in combination with other components such as strontium, vitamin D3, and vitamin K2 has a synergistic effect on bone microstructure and improves bone mineral density (BMD). In this review article, we aim to summarize the regulatory mechanisms of melatonin in osteoblastic differentiation of MSCs and underling involved signaling pathways as well as the clinical potential of using melatonin in bone degenerative disorders.
https://www.sciencedirect.com/science/article/abs/pii/S0300908422002127

Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures
https://pubmed.ncbi.nlm.nih.gov/28130552/

Results: Ten healthy young women between the ages of 20 and 23 were included in our study after obtaining their consent. The mean age of the participants was 21.63 ± 0.94 years. The average height of our patients was 165.72 ± 3.38 m. the average weight of our patients was 59.45 ± 3.5 kg. Vitamin D levels were significantly higher after taking melatonin (mean 13.6 ± 7.9 ng/ml) than after taking placebo (mean 12.68 ± 5.7 ng/ml) during the follicular phase (P=0.001). Whereas, the increase in vitamin D with the intake of melatonin (mean of 15.8 ± 7.8 ng/ml) compared to the taking of placebo (mean of 14.6 ± 5.7 ng/ml) was not significant during the luteal phase (P=0.7). In addition, there was no significant variation in vitamin D levels between the luteal phase and the follicular phase when taking placebo (P= 0.07) and when taking melatonin (P= 0.25).
https://www.endocrine-abstracts.org/ea/0081/ea0081ep634

Pantethine
Because of pantothenic acid’s role in triglyceride synthesis and lipoprotein metabolism, experts have hypothesized that pantothenic acid supplementation might reduce lipid levels in patients with hyperlipidemia [19].

Several clinical trials have shown that the form of pantothenic acid known as pantethine reduces lipid levels when taken in large amounts [20], but pantothenic acid itself does not appear to have the same effects [1]. A 2005 review included 28 small clinical trials (average sample size of 22 participants) that examined the effect of pantethine supplements (median daily dose of 900 mg for an average of 12.7 weeks) on serum lipid levels in a total of 646 adults with hyperlipidemia [20]. On average, the supplements were associated with triglyceride declines of 14.2% at 1 month and 32.9% at 4 months. The corresponding declines in total cholesterol were 8.7% and 15.1%, and for low-density lipoprotein (LDL) cholesterol were 10.4% and 20.1%. The corresponding increases in high-density lipoprotein (HDL) cholesterol were 6.1% and 8.4%.

A few additional clinical trials have assessed pantethine’s effects on lipid levels since the publication of the 2005 review. A double-blind trial in China randomly assigned 216 adults with hypertriglyceridemia (204–576 mg/dl) to supplementation with 400 U/day CoA or 600 mg/day pantethine [21]. All participants also received dietary counseling. Triglyceride levels dropped by a significant 16.5% with pantethine compared with baseline after 8 weeks. Concentrations of total cholesterol and non-HDL cholesterol also declined modestly but significantly from baseline. However, these declines might have been due, at least in part, to the dietary counseling that the participants received.

Two randomized, blinded, placebo-controlled studies by the same research group in a total of 152 adults with low to moderate cardiovascular disease risk found that 600 mg/day pantethine for 8 weeks followed by 900 mg/day for 8 weeks plus a therapeutic lifestyle change diet resulted in small but significant reductions in total cholesterol, LDL cholesterol, and non-HDL cholesterol compared with placebo after 16 weeks [19,22]. Increasing the amount of pantethine from 600 to 900 mg/day did not increase the magnitude of reduction in the lipid measures.

Additional studies are needed to determine whether pantethine supplementation has a beneficial effect on hyperlipidemia independently of, and together with, eating a heart-healthy diet. Research is also needed to determine the mechanisms of pantethine’s effects on lipid levels.
https://ods.od.nih.gov/factsheets/PantothenicAcid-HealthProfessional/#h9

@yerrag It's not the calcium amount but the stress-reducing bioactive compounds in tea having a positive effect on metabolism of bone/glucose.