# data[].attributes.body
Hitting the wall in running means that you have run to the point where you can't go any further and have to stop.

# data[].attributes.attachment_link.readable_text
BioMed Central's Community Manager, Sophie Marchant, as well as thousands of others across the world, will soon be taking part in her first marathon. In the weeks leading up to the event, she looks at some of the research that's been carried out on running, starting with every runner's worst nightmare: injury.

After deciding to sign up to my first marathon, I now find myself not too far from the day it's going to be taking place. A scary but very exciting thought! Preparing for the marathon has been so challenging, and I decided to look at some of the research that's been done in this area. Will it help me through the 26.2 miles?

I don't know about you, but I'm feeling 26.2

Should I? Shouldn't I? Should I? Yes I should! And that was that, decision made, Brighton marathon application sent, and I was a soon-to-be marathoner in training.

I'm absolutely up for the challenge of taking on a marathon. Having completed a few half marathons, among other running events, I was used to running, but little did I realize how hard it would be to push myself farther and farther each week, prepping for the full 26.2.

A popular exercise activity, but what are the risks?

As an exercise that is free, requires very minimal equipment and is easily accessible to everyone, running is one of the most popular forms of exercise worldwide. However, running-related injuries affect many runners, from beginners to ultra-marathoners.

A review found that novice runners are at greater risk of injury, so don't jump straight into a massive run if you're body isn't used to it.

It's important to take care of yourself when running and ensuring you recover well to avoid injury. A review found that novice runners are at greater risk of injury, so don't jump straight into a massive run if you're body isn't used to it. You'll only put yourself out and end up right back where you started.

This is why scientists are working to reduce and understand the risk caused to runners. Research published in Journal of Foot and Ankle Research explains how static foot posture is a risk factor for the development of injury of the lower extremity.

Injury risks associated with different foot types have guided the development of specific running shoes. Many running shoe shops now offer gait analysis so they can recommend trainers which are suited to your foot, compensating for any over- or under-pronation, hopefully reducing the risk of aches and pains.

Barefoot running

Despite this technology, some say the best thing to do is to run barefoot! (Or mimic this with minimal footwear). I suppose when you think about it, the very first humans would have run like this way, way back in the day, so it would be the 'natural' thing to do.

Why should we wear shoes when prehistoric humans had nothing?

Why should we wear shoes when prehistoric humans had nothing? This was more than likely the time that running evolved in the first place - how else would we catch our food or avoid predators?

In fact, other research has found that those running in cushioned shoes actually experience increased pressure in the foot, compared to those running barefoot - leading to increased risk of injury.

According to this review, running barefoot causes you to land slightly more on the ball of your foot (known as a forefoot strike). This has been suggested to reduce the risk of injury by minimizing the impact of your foot as it hits the ground.

Further work showed that those landing on the heel of their foot (rearfoot strike) incurred more injury than those with a forefoot strike. So keep an eye on your technique!

Born to run

Could choosing more minimalist footwear be beneficial? And could the way you land your feet lower the impact to the joints in your foot and leg?

Although running barefoot around the tarmacked roads of Brighton during the marathon doesn't sound appealing (ouch!), could choosing more minimalist footwear be beneficial? And could the way you land your feet lower the impact to the joints in your foot and leg?

When I first started running I used to get a slight pain in my knee. An injury that's so common in runners it's known as 'runners knee', or ' Patellofemoral pain syndrome ' to scientists.

Yet after being advised (by someone who had read ' Born to Run ' - a great book, highly recommend if you're into running!) to land my foot slightly 'toe-first' this ache completely disappeared and has not returned since. Whether I got lucky, or this is actually down to the way my technique changed, who knows!

Research is in the early stages, so don't panic if your marathon is this weekend and you're not landing with a forefoot strike! Everyone does run differently and there are many other factors that could play a role in causing injury. Just go out and enjoy the race, good luck!

# data[].attributes.attachment_link.title
The science behind running: technique and injury - On Health

# data[].attributes.attachment_link.description
BioMed Central's Community Manager, Sophie Marchant, as well as thousands of others across the world, will soon be taking part in her first marathon. In the weeks leading up to the event, she looks at some of the research that's been carried out on running, starting with every runner's worst nightmare: injury.

# data[].attributes.attachment_link.readable_text
After a nice long bout of aerobic exercise, some people experience what's known as a "runner's high": a feeling of euphoria coupled with reduced anxiety and a lessened ability to feel pain. For decades, scientists have associated this phenomenon with an increased level in the blood of β-endorphins, opioid peptides thought to elevate mood.

Now, German researchers have shown the brain's endocannabinoid system-the same one affected by marijuana's Δ9-tetrahydrocannabinol (THC)-may also play a role in producing runner's high, at least in mice ( Proc. Natl. Acad. Sci. USA 2015, DOI: 10.1072/pnas.1514996112).

The researchers hit upon the endocannabinoid system as possibly being involved because they observed that endorphins can't pass through the blood-brain barrier, says team member Johannes Fuss, who's now at University Medical Center Hamburg-Eppendorf. On the other hand, a lipid-soluble endocannabinoid called anandamide-also found at high levels in people's blood after running-can travel from the blood into the brain, where it can trigger a high. "Yet no one had investigated the effects of endocannabinoids on behavior after running," Fuss says.

To explore how endocannabinoids are involved, the team familiarized a group of mice with running on an exercise wheel regularly. Then the researchers split the group into two sets of mice: one that would run for five hours and one that would remain sedentary. Soon after their five-hour run, the rodents in the first group displayed far less anxious behavior than the sedentary set when exposed to a so-called dark-light box test. In this test, a mouse's anxiety is measured by the frequency with which the animal darts from well-lit areas into the dark to hide.

Similarly, mice in the running group had a higher tolerance for pain than those in the sedentary group, as measured by their tendency to jump or lick their paws when placed on a hot plate.

Finally, the researchers performed these same experiments on mice that were given endocannabinoid and endorphin antagonists-molecules that block cannabinoid and opioid receptors in the brain, respectively. The endorphin antagonists did not significantly affect results, but mice treated with endocannabinoid antagonists and mice genetically engineered to lack endocannabinoid receptors were still anxious and sensitive to pain despite having run for hours.

The team's findings suggest that endocannabinoids such as anandamide help cause runner's high. "The authors have moved the field forward by providing such a complete view of how this key reward system is involved in allowing exercise to improve psychological state and pain sensitivity," says David A. Raichlen, an expert in human brain evolution and exercise at the University of Arizona.

The researchers write that other key aspects of runner's high, such as euphoria, are too subjective to study in a mouse model.
This article is reproduced with permission from Chemical & Engineering News (© American Chemical Society). The article was first published on October 5, 2015.

# data[].attributes.attachment_link.authors[].name
Judy Lavelle, Chemical & Engineering News

# data[].attributes.attachment_link.title
New Brain Effects behind "Runner's High"

# data[].attributes.attachment_link.description
After a nice long bout of aerobic exercise, some people experience what's known as a "runner's high": a feeling of euphoria coupled with reduced anxiety and a lessened ability to feel pain. For decades, scientists have associated this phenomenon with an increased level in the blood of β-endorphins, opioid peptides thought to elevate mood.

# data[].attributes.headline
Scroll down on this page for another diagram

# data[].attributes.subject
Scroll down on this page for another diagram

# data[].attributes.attachment_link.readable_text
Introduction

"Give every individual the right amount of exercise, not too little and not too much"

- Hippocrates

Physical activity has long been tied to good health. Hippocrates was guided by his theory of balanced humors to advocate that absolutely everyone, young or old, needs exercise -- but not too much. A landmark 1953 study noted that drivers of public trolleys in London had twice as many acute coronary syndromes as did conductors of the same trolleys; the only notable difference: conductors walked as they collected tickets, while drivers sat. In the decades since this seminal epidemiological observation, nearly every aspect of human physiology has been demonstrated to benefit from exercise, ranging from lung and cardiac function to cognition and aging (). The same decades, however, have witnessed a dramatic sedentarization of the US population (despite the newfound popularity of recreational exercise). Today, the consequences of sedentary lifestyles, synergizing with dramatic increases in caloric intake, are ubiquitous and devastating.

Exercise is a fundamental component of the human condition. Humans are the only primates capable of sustained long-distance running, and this behavior likely significantly shaped the evolutionary departure of humans from other primates. For example, the need for heat dissipation during prolonged physical activity likely favored loss of body hair and the proliferation of sweat glands, thereby considerably altering the human form. Endurance exercise is thus not only good for us, but in fact is part of what defines us. Not surprisingly, the study of exercise, including its mechanics, physiology, and health benefits, has long garnered fascination. Over the last decade, new molecular techniques have ushered a new era of exercise research, focused on understanding fundamental mechanisms. The wealth of new information is staggering. The objective of this review is to provide physicians with key examples of insights gained from this body of work, and to highlight new directions in exercise research that these new molecular tools have opened. The review is illustrative, rather than comprehensive, and we apologize for the omission of many fascinating studies (for some comprehensive reviews, see refs ). The focus will be on endurance exercise and the increasing use of genetically modified mice as a tool to uncover molecular mechanisms of adaptation to endurance exercise.

What goes on inside the muscle

Fiber adaptations: white meat and dark meat

Exercise begins in the contracting muscle. Mechanisms of actin/myosin contraction, of calcium handling, and of neuromotor control have been well studied for a long time. More recently, with new tools in hand, attention has been paid to how muscle adapts to endurance activity. Skeletal muscle is composed of syncitia of thousands of cells, often stretching from tendon to tendon. Different fibers are faced with contrasting tasks, ranging from low-amplitude and repetitive endeavors, like ambulation and maintenance of posture, to sudden bursts of high-amplitude work, such as heavy lifting. Fibers are typically specialized to these tasks (). Fiber types have classically been defined by their myosin heavy chain content, but modern molecular tools have uncovered a high complexity and heterogeneity of fiber types, which sometimes differs between humans and rodents, and which renders simple classification difficult. In broad terms, three major types of human skeletal muscle are type I (slow) oxidative, type IIa (fast) oxidative, and type IIx (fast) glycolytic. The relative amount of these fibers differs between individuals and in various disease states. For example, congestive heart failure and type II diabetes are associated with a lower proportion of type I fibers.

Glycolytic fibers contain myofibrillar proteins that are capable of generating rapid and powerful work, amenable to sudden high-intensity work. This comes at the expense of high calcium fluxes and less efficient use of ATP. In contrast, oxidative fibers contain a more energetically efficient myofibrillar apparatus, more amenable to prolonged activity. Oxidative fibers are also highly vascular, and contain enriched mitochondrial networks, allowing for complete oxidation of fatty acids and other fuels, a much more efficient way to generate ATP than anaerobic glycolysis. High concentrations of myoglobin and cytochromes redden these fibers, hence the term "red fibers". Human muscles mostly contain mixtures of fiber types. In certain organisms, fiber types can segregate. Terrestial fowl, for example, have wings of glycolytic fibers and hindlimbs of oxidative fibers, commonly recognized as 'white meat' and 'dark meat'.

Skeletal muscle gains much of its fiber heterogeneity during development. Nevertheless, adult muscle retains significant plasticity. Endurance activity can significantly expand mitochondrial and vascular networks and in part change the myofibrillar content in muscle fibers (). How does this process occur? The last 10 years have begun to answer this question at the molecular level (). Much of this work has relied on the study of genetically modified mice (e.g., ). Rodents are natural-born endurance exercisers: provided with in-cage running wheels, most mice will voluntarily run 5-8 kilometers per night. Although this level of exercise does not precisely model the human condition, the ability to model endurance exercise in an organism amenable to genetic manipulation has proven invaluable. Conceptually, the adaptation process can be divided into mechanisms that sense endurance activity, and mechanisms that carry out the desired adaptations ().

How does muscle sense exercise activity? Nerves and energy

Key molecular sensors of exercise include the calcium oscillations and other signaling cascades activated by neural stimulation, and the profoundly altered metabolic state of contracting myofibers.

Stimulation of muscle by motor nerves generates cytosolic calcium transients that are detected by various intracellular pathways, including those regulated by the calcium/calmodulin-modulated phosphatase (calcineurin) and kinase (CaMK). Continuous low-amplitude transients, typical of endurance activity, activate calcineurin. Transgenic over-expression of calcineurin in skeletal muscle of mice promotes the formation of slow red fibers. Conversely, genetic deletion of calcineurin or treatment with calcineurin inhibitors has the opposing effect, blocking exercise-induced adaptations. CaMK is likely another decoder of calcium transients. CaMKII is the predominant isoform in skeletal muscle, but experiments with transgenic expression of a constitutively active CaMKIV isoform showed that CaMK can promote the formation of slow red fibers. Conversely, mice with decreased CAMKII activity have lower expression of slow genes. Sensing of calcium transients thus appears to be a critical transducer of motor nerve activity.

Endurance exercise also elicits profound metabolic changes that can be sensed to trigger long-term adaptations. A key sensor is the AMP-activated protein kinase (AMPK). AMPK integrates multiple signals that alert to cellular energetic insufficiency, such as elevated AMP/ATP ratios. Once activated, AMPK triggers metabolic pathways that can compensate for this deficiency, such as mitochondrial biogenesis, while inhibiting anabolic pathways that consume ATP. Mice engineered to lack AMPK activity in skeletal muscle run poorly and lack nearly half their mitochondrial content. Conversely, mice engineered to express an activated form of AMPK have higher mitochondrial content, more β-oxidation, and are resistant to fatigue. Other metabolic sensors are less conclusively implicated in exercise adaptations, but likely also play a role, including the aging-associated sirtuin (SIRT) family of proteins. SIRTs are deacetylating enzymes that require NAD and sense NAD/NADH ratios, which reflect cellular redox state. The NAD/NADH ratio, and thus likely SIRT activity, increases significantly with exhaustive exercise. SIRT activity is also enhanced by AMPK, thus linking these two pathways.

Exercise-induced hypoxia or ischemia has also long been advocated as a potential mediator of muscle adaptation to endurance exercise. Acute exercise reduces the partial pressure of oxygen in the vicinity of myoglobin to <4mmHg (<1/40 th of atmospheric), which is sufficiently low to activate the critical hypoxia-sensor hypoxia-inducible factor-1α (HIF-1α). However, it is not clear that this level of hypoxia is achieved in the nucleus, where HIF-1α resides. Moreover, mice genetically modified to lack HIF-1α in muscle have higher, rather than lower, oxidative capacity. Conversely, people living at higher altitudes, where oxygen tension is low, tend to have less oxidative muscle, rather than more. It thus remains uncertain if hypoxia mediates pro-oxidative adaptations to endurance exercise in muscle.

In summary, nerve stimulation and calcium signaling, and metabolic changes that occur in the contracting myofiber, are likely the key instigators of adaptations to exercise in muscle. These signals vary dramatically in both quality and quantity in response to exercise of different types, intensities, and durations. This last point poses a challenge to exercise research. The effects of exercise can differ widely depending on exercise type, dose, intensity, or frequency, and inter-individual adaptations to exercise also vary widely. Thus a key advantage of studying rodent models, i.e. their genetic and phenotypic homogeneity, can also be a drawback. Experimental exercise regimens are not fully standardized, and comparing studies can sometimes be difficult. It is also difficult to scale rodent exercise to human exercise, e.g., how much does 5 kms of voluntary running overnight by a 40g mouse equate to in human terms? Nevertheless, the ability to model endurance exercise in an organism that is amenable to genetic manipulation continues to prove invaluable. How the complex inputs of endurance exercise are integrated thus remains incompletely understood. Metabolic signaling in particular is likely to be a prominent focus of research in the forthcoming years.

How does muscle reprogram in response to exercise? Plug-and-play

The signals discussed above impinge on a number of regulators of gene expression that reprogram myofibers from glycolytic to more oxidative fibers. Two important concepts guide this process. First, these regulating factors typically control broad programs. The transcriptional regulators peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and PGC-1β, for example, can activate an entire program of mitochondrial biogenesis, including all components of the electron transport chain, the TCA cycle, and fatty acid β-oxidation. Simple transgenic expression of PGC-1 in skeletal myofibers dramatically increases mitochondrial content, yielding mice with improved endurance exercise capacity and peak oxygen uptake (). Conversely, deletion of both PGC-1 isoforms in muscle drastically reduces oxidative capacity. Most signaling pathways described above, including calcineurin, p38 MAPK, adrenergic signaling, and SIRT proteins, impinge on the PGC-1s, and do so in a variety of molecular ways, including protein phosphorylation and deacetylation, and induction of gene expression. The PGC-1s are thus potent nodal points of gene regulation used by myofibers to coordinate adaptations to exercise. A number of other such regulators exist (e.g., ).

A second important concept is that these nodal points regulate defined and modular programs (). For example, the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) modulates the use of fatty acid as a fuel by regulating the specific subset of genes encoding rate-limiting enzymes for fatty acid transport and oxidation. Similarly, a small set of transcription factors including nuclear respiratory factor (NRF-1), NRF-2, and estrogen-related receptor α (ERRα), control the complex generation of new mitochondria, including control of the replication and expression of the mitochondrial genome. The specific makeup of the myofibrillar apparatus, on the other hand, appears to be regulated primarily by myocyte enhancer factor-2 (MEF2) and nuclear factor of activated T-cells (NFAT) transcription factors, modified in turn by a number of histone deacetylases (HDACs). Any these independent programs can be coordinately modulated by the PGC-1s or other coordinating agents. Cellular reprogramming can thus occur in a modular fashion, with a relatively simple interface between input and output, analogous to plug-and-play.

An important implication of this modular regulatory concept is that modules can be activated independently, even if there is often significant crosstalk between them. For example, genetic deletion of both PGC-1α and β in murine muscle leaves the myofibers metabolically crippled, but has almost no effect on the myofibrillar content of the myofibers. The myofibrillar and metabolic responses to endurance exercise thus appear genetically dissociable and are likely regulated by exercise differently. In a highly simplified schema, it can be suggested that calcium signaling, occurring via calcineurin and CAMKII, predominantly affects myofibrillar adaptations, while metabolic sensing, via AMPK and other sensors, predominantly affects mitochondrial and other metabolic adaptations.

In summary, nerve activity and metabolic changes are transduced to a cadre of transcriptional regulators that modularly translate this information into specific muscle adaptations. Other forms of modulation are superimposed on these gene regulatory pathways. Recent exciting additions include epigenetic modifications, and micro RNAs (miRNAs). Methylation of DNA had long been thought to be a slow and meta-stable way to regulate gene expression, sometimes even allowing transmission of information across generations. It is now clear, however, that even a single bout of exercise can dramatically alter the methylation of certain genes, including PGC-1α. This surprising finding unveils entirely new potential mechanisms of exercise adaptations. Similarly, the recent discovery of miRNAs has also opened new avenues of potential regulation. miRNAs are short RNAs that potently inhibit gene expression by binding to target mRNAs and causing their degradation or blocking their translation. Skeletal muscle expresses a number of miRNAs, dubbed myomiRs. For example, miRNAs 208b and 499 are co-expressed with slow MHC genes and act to inhibit expression of genes specific to fast myofibers, thus reinforcing the slow program. A number of miRNAs are regulated by exercise, but their role in exercise adaptations remains unknown, and appropriate mouse models have yet to be generated. Some miRNAs are also secreted into the circulation, raising the enticing notion that they may act as endocrine signals. The study of miRNAs as potential mediators of adaptations to exercise remains in its infancy, but holds great promise.

Beyond fiber types: other important ways that exercise changes skeletal muscle

Discussions of metabolic adaptations to endurance exercise are often limited to mitochondrial biogenesis, but mitochondrial reprogramming is likely much more complex. Mitochondria are traditionally portrayed as static, oval, organelles. Recent work has challenged this view and revealed mitochondria as forming a large and dynamic reticular network, constantly fusing and breaking apart in a highly coordinated manner. These fusion/fission events appear imperative for normal mitochondrial function. For example, they allow for constant redistribution of both genetic and biochemical components between separate mitochondria, a process that is somehow used to segregate dysfunctional mitochondrial components and to remove them from the network via autophagy (discussed below). The regulation of mitochondrial fusion is controlled by mitofusins (Mfn1 and Mfn2) on the outer mitochondrial membrane and optic atrophy type 1 (Opa1) on the inner mitochondrial membrane, while fission is regulated by dynamin-related protein (Drp1) and Fission 1 (Fis1). Exercise induces the expression of most of these genes in both human and rodent muscle. PGC-1α induces the expression both Mfn1 and Mfn2 via activation of ERRα. Deletion of both Mfn1 and Mfn2 in mouse skeletal muscle leads to profound lactic acidosis in response to exercise. These observations thus suggest that mitochondria in muscle are not static objects, and that mitochondrial dynamics play an important role in exercise adaptations. The specifics of that role remain poorly understood.

Autophagy (Greek for "self-eating") is a process by which cells selectively move damaged organelles like mitochondria to the lysosome for subsequent degradation. This quality control process is critical for maintaining tissue integrity. The process also appears important for adaptations to exercise. Exercise strongly and rapidly induces autophagy in skeletal muscle and numerous other tissues. Moreover, genetically modified mice that lack stimulus-induced autophagy have drastically reduced treadmill running capacity, suggesting that autophagy is important for endurance capacity. On the other hand, inappropriate autophagy in muscle can be pathological, as seen after treating mice with doxorubicin, and in this case exercise is protective. The interplay between exercise and autophagy in muscle is thus complex. Mitochondria are also not the only organelles that respond to exercise. Exercise, for example, also activates the unfolded protein response (UPR) in the sarcoplasmic reticulum. Mice that lack activating transcription factor 6 (ATF6), a key regulator of the UPR, exhibit severe exercise intolerance. In sum, burgeoning data with novel mouse models suggest that exercise helps to maintain homeostasis of multiple organelles in skeletal muscle, with likely important implications for the health of the whole organism.

Exercise also promotes neovascularization in skeletal muscle. Exercise-induced angiogenesis (EIA) is a physiologic process, in contrast to most post-developmental angiogenesis (e.g., neoplasms, retinal diseases). Exercise also remains the most efficacious intervention for peripheral artery disease (PAD). Understanding EIA could thus inform novel approaches for the treatment of PAD. The prevailing paradigm had been until recently that metabolic demands created by exercising muscle cause a supply/demand mismatch, leading to activation of ischemic sensors like AMPK and HIF-1α. Recent data with genetically modified mice, however, do not support this notion. Mice lacking AMPK activity in skeletal muscle have intact EIA, and mice lacking HIF-1α in skeletal muscle have more, rather than fewer, microvessels. On the other hand, mice lacking PGC-1α in skeletal muscle lack the capacity for EIA (although, interestingly, not for exercise-induced mitochondrial biogenesis) Conversely, mice transgenically over-expressing PGC-1 in skeletal muscle have dramatic increases in microvascular density, and are protected in a hindlimb ischemia model of PAD. β-adrenergic and other signals induce PGC-1α in skeletal muscle, and PGC-1α directly activates expression of the canonical angiogenic factor VEGF in a HIF-independent fashion. Physiological angiogenesis in muscle is thus likely triggered more preemptively by nerve activity than reactively by ischemia.

Stepping outside the muscle -- Is skeletal muscle an endocrine organ?

Experiments over the last decade have made it increasingly clear that, in response to exercise, muscle secretes into the circulation sometimes copious amounts of factors, now known as myokines. In retrospect, this is perhaps not surprising: muscle is the largest organ in the body, and can command up to 80% of cardiac output during exercise. Muscle is thus ideally suited to disseminate blood-borne substances in response to exercise.

The interleukin IL-6 was one of the earliest discovered myokines, and remains one of the most studied (). Muscle contraction and exercise increase the expression of IL-6 in muscle and levels of IL-6 in the circulation by as much as 100-fold. In an autocrine and paracrine fashion, IL-6 increases glucose uptake and fatty acid oxidation in muscle, thus facilitating fuel consumption locally. At the same time, in an endocrine fashion, IL-6 stimulates lipolysis in adipose tissue and gluconeogenesis in the liver, both of which increase fuel delivery back to the muscle. Recently, IL-6 secreted by muscle has also been shown to crosstalk with the gut and pancreas to regulate insulin homeostasis. IL-6 stimulates the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L-cells and pancreatic α cells. GLP-1, in turn, potentiates insulin secretion from pancreatic β cells. IL-6 −/− mice fail to induce GLP-1 during exercise, and develop mature onset obesity and glucose intolerance. Conversely, exogenous IL-6 improves insulin sensitivity, but not in GLP-1 −/− mice. This IL-6/GLP-1 axis thus likely mediates the enhanced insulin action seen in the immediate post-exercise period. Interestingly, GLP-1 may also contribute to cognitive effects of exercise: GLP-1 KO mice have learning deficits, while GLP-1 agonists improve memory tasks in mice (see below for discussion of cognitive effects of exercise). In sum, muscle-derived IL-6 appears to help integrate the entire organism response to the needs of exercising muscle (). Other interleukins and traditional inflammatory cytokines, including IL8 and IL15, also likely double as exercise-induced myokines, though their functions are less clear.

Irisin is a different potential myokine that has received much attention recently. Irisin is a soluble cleavage product of fibronectin type III domain containing 5 ( FNDC5), a transmembrane protein found in myocytes. Release of irisin, acting via an as yet unknown receptor, "browns" nearby white fat cells that are interdigitated between muscle fibers. The uncoupler UCP1 and other markers of brown fat are induced in these cells, leading to a futile cycle of uncoupled mitochondrial respiration, and dissipation of heat. Paracrine release of irisin thus promotes consumption of fuels. Consistent with this, exogenous administration of irisin ameliorates diet-induced obesity in mice. Circulating levels of irisin correlate with endurance capacity, and increase during exercise (though some controversy exists on this point), but the endocrine effects of irisin remain uncertain. It is also unclear, but interesting, why exercise should promote wastage of fuel in adjacent brown fat cells, when energy efficiency would seem preferable when exercising. One possibility is that irisin is in fact primarily part of a shivering program to produce heat, rather than an exercising program. Interestingly, irisin is also induced by myostatin, another molecule secreted from myocytes. Myostatin inhibits muscle growth, and has received wide attention as a potential target to preserve muscle mass. Deletion of myostatin in mice leads to secretion of irisin and browning of white fat.

Numerous other myokines exist that can have profound effects on systemic metabolism. FGF21 is secreted from muscle in response to mitochondrial dysfunction or anabolic signals and protects from obesity and diabetes, likely in part by inducing a hypermetabolic state. Myonectin secretion increases in response to numerous metabolic perturbations, including exercise, and modulates systemic handling of fatty acids. Yet other myokines, like VEGF and other angiogenic factors (see above), may function primarily as paracrine factors. Exercise for example liberates membrane-bound neuregulin, freeing it to both stabilize neuromuscular junctions and promote glucose uptake in myocytes. Similarly, the neurotrophin Brain Derived Neurotrophic Factor (BDNF) and the interleukin-like LIF are induced by exercise and may promote fatty acid oxidation in muscle. BDNF may additionally contribute to muscle-brain crosstalk in exercise (see below).

In sum, exercise (and other metabolic stimuli) triggers from muscle the secretion of proteins and small molecules that integrate systemic adaptations to the demands of exercise. The study of these factors is still in an early discovery phase. Skeletal muscle may well be a large under-appreciated endocrine organ.

Exercise and the heart

The effects of exercise on the heart have been reviewed recently in Circulation and will only briefly be covered here. The adult human heart retains considerable plasticity. This is most evident in the maladaptive cardiac remodeling that often follows myocardial infarction, chronic hypertension, and other cardiac insults. Efforts to impede this pathologic remodeling, via blockade of the adrenergic and angiotensin systems, form the mainstay of current heart failure management. Despite these treatments, however, the 5-year mortality of patients with heart failure remains >30%. New and qualitatively different therapeutic approaches are clearly needed.

Endurance exercise can induce cardiac mass by as much as 20%. This physiological remodeling differs significantly from the pathologic remodeling noted above. In model organisms, exercise similarly induces cardiac hypertrophy, and improves outcomes after experimental myocardial infarct and other cardiac insults. Understanding these physiological remodeling pathways may thus afford therapeutic opportunities that differ from the existing paradigm of blocking neurohormonal activation. Many effects of exercise on the heart are indirect, including reductions in BMI and improvements in insulin sensitivity. Other effects, however, are clearly direct. Insulin-like Growth Factor-1 (IGF-1) engages the IGF-1 receptor on cardiomyocytes and activates the intracellular PI3K/Akt pathway. This leads to inhibition of apoptosis, improvements in metabolism and calcium handling, and activation of the mTOR-dependent hypertrophic pathway. As with skeletal muscle, concomitant adrenergic input is likely also critical for exercise-induced cardiac adaptations, in this case via β3 receptors and increased nitric oxide (NO) bioavailability. Other pro-physiological hypertrophy mechanisms likely exist.

One of the exciting developments in cardiac research in the last decade has been the realization that the adult heart harbors at least the potential for endogenous regeneration. Adult newts and zebrafish, and newborn mice, can regenerate seemingly normal hearts after apical resection. In humans, calculations based on the incorporation of ambient radioactivity generated in the 1950's by above-ground testing of nuclear bombs has conclusively demonstrated that human cardiomyocytes can turn over, albeit slowly. It remains controversial whether this turnover stems mostly from the replication of existing cardiomyocytes or from resident or circulating stem cells. In either case, data are emerging to suggest that exercise may activate this process. Endurance exercise in rodents induces measurable replication of cardiomyocytes. Transcriptional profiling of exercising rodent hearts revealed that endurance exercise represses expression of the transcription factor CCAT-enhancer binding protein (C/EBPβ). Haploinsufficiency of C/EBPβ in mice led to physiological cardiac hypertrophy and cardiomyocyte proliferation, thus mimicking some effects of exercise on the heart. Akt inhibits C/EBPβ, and may thus promote cardiomyocyte proliferation. Other Akt-dependent pathways likely exist. The mechanisms underlying these observations are being studied intensively.

A longstanding and often controversial debate exists over the ideal amount of exercise needed for cardiac protection, and the possibility that too much exercise may have ill-effects. A link between strenuous exercise and sudden death is well-established, but can only partly be explained by the well-known high prevalence of idiopathic hypertrophic cardiomyopathy in this population. Strenuous exercise may cause disproportionate adaptations in the right ventricle (RV), which have been postulated to predispose to arrhythmias, most commonly atrial fibrillation. 12 weeks of aggressive exhaustive exercise training in rats led to RV enlargement, diastolic dysfunction, and fibrosis, and increased susceptibility to triggered VT. The changes were likely caused by pathologic angiotensin II (ATII) activation, because angiotensin converting enzymes inhibitors (ACEIs) reversed the phenotype, but the mechanisms of cardiotoxicity by strenuous exercise remain unclear. These studies highlight a number of important issues: 1) the effects of exercise differ depending on exercise type, intensity, or frequency; 2) the appropriate "dose" of endurance exercise in humans is likely variable, because inter-individual responses to exercise vary widely; 3) the "dose" that maximally confers cardiovascular protection likely differs from that which maximally confer cardiovascular fitness; 4) rodents provide powerful tools with which to probe the molecular mechanisms of exercise adaptations, but they are poor models to ascertain the optimal "dose" of exercise in humans, because specific rodent and human exercise regimens are difficult to compare (i.e., poor scalability); and 5) the Hippocratic instruction of tempered exercise likely holds true today as it did 2500 years ago.

Exercise and the brain - active body and mind

There is little doubt that exercise improves mental health. Physical activity correlates well with mental well being, especially in old age. Exercise significantly counteracts at least moderate depression, and can prevent loss of memory. Indeed, mental well-being post-MI is a strong predictor of outcomes, and improvements in mental health may well explain a significant part of why physical activity is so beneficial to cardiovascular health.

Early and exciting inroads are being made into understanding the molecular mechanisms that underlie these neuronal benefits of exercise. One focus has been on a small roster of secreted neurotrophic factors, including BDNF and VGF. BDNF is a well-studied neurotrophin, thought to be critical for learning and memory. Exercise stimulates BDNF expression in the hippocampus, the seat of learning, and raises levels of BDNF in venous return from the brain in humans. Exercise has been known to stimulate neurogenesis in the adult hippocampus, and the increases in hippocampal size seen in exercising humans correlates with exercise capacity (VO2max) and circulating BDNF. Neutralizing BDNF, either with blocking antibodies or by genetic deletion in BDNF +/− heterozygote animals, prevents the ability of exercise to improve learning. BDNF likely mediates these responses to exercise by modulating neuronal and axonal plasticity, and may do so in part via activating pro-energetic pathways including PGC-1α and mitochondrial biogenesis. BDNF is also likely modulated by other neurotrophic factors, including IGF-1, which is also significantly induced in the hippocampus by exercise.

Exercise also ameliorates major depression in humans, and produces antidepressant effects in rodent models. Interestingly, transcriptional profiles of rodent hippocampus after exercise and after treatment with serotinergic antidepressants yield similar results, suggesting similar mechanisms of action. The presence of the peptide VGF increases in the hippocampus during exercise, and intracerebroventricular infusions of VGF produce antidepressant-like effects in mouse and rat behavioral models. Conversely, antidepressant responsiveness to exercise in the same models was blocked in heterozygous VGF +/− mice. VGF is regulated by BDNF, expression of which is also low in depression. Like BDNF, VGF likely modulates synaptic plasticity in response to exercise. Other factors also exist to mediate the anti-depressant effects of exercise. The macrophage migration inhibitory factor (MIF), for example, likely contributes to activation of BDNF during exercise, and MIF −/− mice have a blunted antidepressant response to exercise. Together, these small neurotrophic factors thus appear to mediate important beneficial neurologic changes in response to exercise.

The neurological benefits of exercise are not limited to depression and memory. Exercise also benefits neurodegenerative illnesses like Parkinson disease and Alzheimer's disease, and this can be recapitulated in rodent models. Mice lacking one copy of BDNF fail to benefit from exercise, again implicating this factor in exercise-induced neuroplasticity. A genetic model of spinocerebellar ataxia (SCA), caused by a polyglutamine expansion in the Ataxin-1 protein, is also markedly improved by exercise. Again, a neurotrophic factor induced by exercise is implicated: epidermal growth factor (EGF). A downstream effector of EGF, Capicua (Cic), interacts directly with ataxin and is strongly inhibited by exercise. Genetic reduction of Cic in Cic +/− heterozygote mice rescues multiple abnormal phenotypes in the SCA mouse model, thus mimicking the effects of exercise.

Lastly, although there have been great inroads in recent years in the understanding of neural networks that regulate appetite for food, much less has been done to ask the same question of exercise: what regulates appetite for exercise? Different rodent strains have different appetites for voluntary exercise, and rodents can be selectively bred for high versus low voluntary physical activity, indicating the existence of a strong genetic component. Genetic quantitative trait loci that track with these differences can in fact be mapped, but their function remains unknown. Importantly, subsequent studies reveal few differences in skeletal muscle composition between these selected mouse cohorts, indicating that central networks likely regulate motivation for exercise. Initial experiments, mostly pharmacological, implicate the dopaminergic system, underscoring links to movement disorders like Parkinson's disease. Definitive genetic experiments in mice, akin to those performed to evaluate the neurobiology of food satiety, have not yet been reported.

In summary, complex mechanisms underpin the dramatic cognitive and neural benefits of exercise. A number of exercise-induced neurotrophic factors are providing the initial molecular clues to decipher these mechanisms.

Exercise and Aging

Exercise capacity predicts longevity, and physical fitness is one of the best predictors of health in elderly individuals. For instance, a study of 538 aged runners and 423 age-matched controls found that only 15% of the runners died over 21 years, compared to 34% in the control group. Controlled experiments to prove causality are of course difficult in humans, but animal experiments also have strongly supported the conclusion that exercise prolongs life. Forcing rodents to exercise prolongs their average longevity and improves their aged health status. Evolution-in-the-lab experiments, in which rodents with higher exercise capacity were selected and interbred over numerous generations, revealed that longevity was co-selected with exercise capacity. Exercise is thus linked to long life both in animal models and in man.

How does exercise prolong life? Does it do so by individually averting each of the illnesses of aging, or does it have a more general and fundamental anti-aging power? The question is difficult to answer in part because the process of aging remains poorly understood. A number of theories of aging exist. The mitochondrial theory of aging, borne of the earlier "free radical theory of aging" proposed in 1956 by Denham Harman, posits that unstable free radicals produced by mitochondria are an obligatory byproduct of aerobic life. These radicals damage biomolecules, especially mtDNA, leading to progressive mitochondrial dysfunction, worsening free radical generation, and thus a vicious cycle of oxidative damage that ultimately limits mammalian lifespan. Accumulation of oxidative damage to DNA, proteins, and membranes can be seen in aged tissues across phylogeny, including humans. Recent experiments in genetically modified mice have supported the mitochondrial/free radical theory of aging. Transgenic over-expression of antioxidant enzymes increases lifespan in mice. Conversely, mice that harbor an error-prone mitochondrial DNA polymerase rapidly accumulate mtDNA mutations and demonstrate multiple aspects of aging, including graying fur, kyphosis, degenerative diseases, and premature death.

Exercise appears to favorably impact these processes, but the details of how this occurs remain murky. Exercise reduces oxidative damage. Strikingly, endurance exercise reverses nearly all of the aging phenotypes in the "mutator" mice described above, including their multisystem pathology and premature mortality; the mice are nearly indistinguishable from control mice. Even more strikingly, exercise prevents accumulation of mtDNA mutations in these "mutator" mice. Exercise thus somehow activates systemic mechanisms of mitochondrial quality control, even outside skeletal muscle. There is indeed growing appreciation that exercise induces mitochondrial adaptations in tissues beyond skeletal muscle, and, as noted above, exercise also systemically activates autophagy/mitophagy.

PGC-1α and its powerful regulation by exercise may again play a central role in these processes. PGC-1α simultaneously induces mitochondrial biogenesis and anti-ROS programs. Mice that lack PGC-1α accumulate ROS-mediated damage and display dramatically accelerated neuro-degeneration. Strikingly, transgenic mice with boosted PGC-1α expression in skeletal muscle have increased longevity and are healthier in old age. As noted above, these transgenic mice recapitulate many aspects of endurance exercise adaptations, but they are not more active at baseline. Boosting PGC-1α only in skeletal muscle is thus sufficient to prolong life in rodents. The same approach does not rescue premature aging in mtDNA "mutator" mice, which suggests either a threshold effect or more unappreciated complexity. Overall, these observations again point to the powerful influence of muscle on the rest of the body, and again suggest the existence of organ crosstalk via myokines. The existence of circulating "rejuvenating" factors has been supported by parabiosis experiments (see above for description of the approach): old animals in young-old heterochronic parabiotic pairs reacquire numerous attributes of youth, including tissue and stem cell regenerative potential.

Telomeres are nucleoprotein complexes at chromosome ends that preserve chromosomal integrity. The telomere theory of aging holds that cell divisions causes progressive telomere attrition, culminating in activation of p53, the 'guardian of the genome', leading to cellular apoptosis and senescence. Stem cells, which are hyper-proliferative, are especially prone to telomere erosion. Loss of resident stem cells impairs turnover and repair capacity of tissues and slowly leads to tissue degeneration. Short telomeres in human peripheral blood leukocytes correlates with higher mortality rates in individuals more than 60 years old, and telomere length predicts good health and longevity in centenarians and their offspring. Telomeres are kept from eroding by the enzyme telomerase. Mice with dysfunctional telomerase develop numerous accelerated aging phenotypes, supporting the telomere theory of aging. Similarly, mice engineered with hyper-active p53 alleles also display premature aging. Exercise appears to favorably impact these processes as well, but again the mechanisms are not clear. Exercise activates telomerase and inhibits telomere erosion in circulating cells in mice and humans. Recent data have also indicated that telomere shortening and p53 activation leads to repression of PGC-1α and mitochondrial capacity. This observation links theories of aging, and suggests that activation of PGC-1α by exercise may thus interfere with aging at this level as well.

In summary, exercise undeniably attenuates the aging process. Early indications are that common, central mechanisms underlie aging in differing tissues, and that exercise may target these key pathways. Longevity and physical inactivity are both on the rise in the industrial world. Studies probing into the mechanisms by which exercise influences aging thus represent one of the most exciting frontiers of exercise research.

Exercise in a pill - is it a dream?

Finding a "gymnomimetic" pill that fully recapitulates exercise is likely an impossible dream. The sheer complexity and pleitropic effects of exercise almost certainly preclude such a simple approach. Nevertheless, understanding the numerous molecular pathways modulated by exercise may enlighten approaches to mimic individual effects of exercise. Pharmacologic activation of AMPK or SIRT in mice, for example, recapitulates certain aspects of exercise, including increases in exercise capacity. Activating individual effects of exercise could, for example, serve as adjunct treatment to exercise programs.

The challenges to find even partial exercise mimetics, however, are many. First, the number of potential targets identified so far remains small. Efforts to understand the molecular underpinnings of exercise should thus continue. Second, most of these targets, such as transcription factors or coactivators, are not easily "druggable". In this light, recent developments with myokines are particularly exciting, because circulating and extracellular factors provide more readily accessible pharmaceutical targets. Early developments with miRNAs also hold promise in this context, because miRNAs are proving to be readily targeted in humans with antiMirs and miRNA analogs. And third, because gymnomimetics would likely be used for prevention or chronic treatment, safety profiles would need to be nearly perfect. This is a serious problem, because exercise by its nature has pleitropic effects, which is generally not ideal for a pharmaceutical agent. In this last context, initial proof-of-concept therapeutic efforts may have more success by targeting patient populations with few other options, because such patients would more likely be willing to accept adverse side effects. For example, genetic induction of PGC-1α in muscle in mice reduces degeneration in a murine model of Duchene Muscle Dystrophy. Lastly, the gymnomimetic field is also muddled by contrasting goals. Whereas many look to exercise for mechanistic insight into disease prevention, many in the sporting arena seek performance-enhancement.

In short, although the physiology of exercise has been investigated for centuries, the molecular biology of exercise remains a young science. The translation of molecular findings to therapeutics so far remains more of a promise than a reality.

# data[].attributes.attachment_link.title
Running Forward: New Frontiers in Endurance Exercise Biology

# data[].attributes.attachment_link.description
"Give every individual the right amount of exercise, not too little and not too much" - Hippocrates Physical activity has long been tied to good health. Hippocrates was guided by his theory of balanced humors to advocate that absolutely everyone, young or old, needs exercise -- but not too much.

# data[].attributes.attachment_link.readable_text
Heather Topham Wood

Heather Topham Wood is a seasoned writer whose work has appeared in numerous publications, including USA Today, Gadgetell, Feel Rich and Step in Style. Heather is a published novelist with six Amazon bestsellers and a contract through Crescent Moon Press. She holds a bachelor's degree in English from TCNJ.

Since running is a high-intensity exercise, your heart rate will increase greatly during exertion. The speed and distance of the run affects your heart rate reading. Using a heart rate monitor can help you run within a target training zone. Most heart rate monitors for running require securing a chest strap around your body and wearing a wireless receiver on your wrist. Check with your doctor before trying any new exercises or exercising at a higher intensity.

Video of the Day

Calculate your maximum heart rate before you start monitoring your progress during runs. For men, the maximum heart rate is 220 minus your age. For women, subtract 88 percent of your age from 206. For instance, a 40-year-old man will have a maximum heart rate of 180, and a 40-year-old woman will have a maximum heart rate of 171.

During distance runs, exercising at your target heart rate can improve aerobic capacity and muscle cell adaptation. A distance run is one that's longer than 5 miles and involves you working at 70 to 75 percent of your maximum heart rate. Use this heart rate on recovery run days or as part of your preseason training plan. To increase your lactate threshold, run at 80 to 90 percent of your maximum heart rate. Your lactate threshold is the level at which lactic acid is released into your bloodstream.

Running at your target heart rate during interval training sessions improves your max oxygen consumption, increases cardiac output, enhances anaerobic endurance and increases the rate of lactic acid removal from your body. Long intervals of three to five minutes should be run at 95 percent of your max heart rate with short rest periods in-between. Short intervals of no more than 90 seconds can be run at 100 percent of your max heart rate and should have long rest sessions.

If you are new to exercise, do not start running at 70 percent or higher of your maximum heart rate immediately. The American Heart Association suggests you work at 50 percent of your maximum heart rate. By six months of regular running, you should be able to exercise comfortably at 85 percent of your max heart rate. Keep in mind that certain medications, like blood pressure drugs and medical conditions, like heart disorders, can affect your heart rate readings.

# data[].attributes.attachment_link.title
How Does Running Affect Your Heart Rate?

# data[].attributes.attachment_link.description
Since running is a high-intensity exercise, your heart rate will increase greatly during exertion. The speed and distance of the run affects your heart rate reading. Using a heart rate monitor can help you run within a target training zone. Most heart rate monitors for running require securing a chest strap around your body and wearing a wireless...

# data[].attributes.attachment_link.readable_text
Abstract

This factsheet explains how exercise affects the lungs, how breathing is influenced by activity and the benefits of exercise for people with and without a lung condition.

Regular physical activity and exercise improves quality of life, whether you are healthy or you have a lung condition. Many people associate keeping fit with maintaining a healthy heart, losing weight and reducing the risk of illnesses such as diabetes, but exercise also helps keep lungs healthy.

This factsheet explains how exercise affects the lungs, how breathing is influenced by activity and the benefits of exercise for people with and without a lung condition.

What is exercise and how much should I do?

Any type of physical activity counts as exercise. It could be planned sport such as running, swimming, tennis or bowls, an exercise training programme, or a hobby such as cycling or walking.

It could also include physical activities which are part of your daily life, such as gardening, cleaning or walking to the shops.

In order to stay healthy, you should do 30 minutes of moderate exercise five days per week. For a healthy person, moderate exercise might be walking at a pace of 4 to 6 km per hour. If you have a lung problem, you would need to walk fast enough to make you moderately breathless.

What happens to my lungs when I exercise?

During exercise, two of the important organs of the body come into action: the heart and the lungs. The lungs bring oxygen into the body, to provide energy, and remove carbon dioxide, the waste product created when you produce energy. The heart pumps the oxygen to the muscles that are doing the exercise.

When you exercise and your muscles work harder, your body uses more oxygen and produces more carbon dioxide. To cope with this extra demand, your breathing has to increase from about 15 times a minute (12 litres of air) when you are resting, up to about 40-60 times a minute (100 litres of air) during exercise. Your circulation also speeds up to take the oxygen to the muscles so that they can keep moving.

When your lungs are healthy, you keep a large breathing reserve. You may feel 'out of breath' after exercise, but you will not be 'short of breath'. When you have reduced lung function, you may use a large part of your breathing reserve. This may make you feel 'out of breath', which can be an unpleasant feeling, but it is not generally dangerous.

What are the benefits of exercise?

It is normal to get breathless during exercise. However, regular exercise can increase the strength and function of your muscles, making them more efficient. Your muscles will require less oxygen to move and they will produce less carbon dioxide. This will immediately reduce the amount of air you will need to breathe in and out for a given exercise. Training also improves your circulation and strengthens your heart.

Exercise will improve your overall physical and psychological well-being. It can decrease the risk of developing other conditions such as stroke, heart disease and depression. Regular exercise is also one of the most important interventions to prevent the onset of type-II diabetes.

What can I do to help my lungs cope with exercise?

The most important thing to do to keep your lungs healthy is to look after them. Smoking will affect your ability to undertake physical activity and reach your true potential. If you quit smoking, you are likely to be able to exercise for longer as early as two weeks after your last cigarette. The ELF factsheet on 'Smoking and the lungs' can provide more information on this topic.

Can exercise cause any problems with the lungs?

People who follow high-intensity training regimes, or who regularly train in certain environments, may be at risk of developing exercise-induced asthma, or a condition known as bronchial hyperresponsiveness in which the airways become blocked after exercise. If take bronchodilators, you should normally take these 10 minutes before you exercise to prevent exercise-induced bronchoconstriction. Your doctor can give you advice on this.

Scientists believe this is caused by harmful substances in the environment in which they are training, such as chlorine in a swimming pool, or cold dry air on a ski slope. Endurance athletes have the potential to inhale more harmful substances into their lungs, as they are exposed to these conditions for longer periods of time. Our factsheet, 'Asthma in elite athletes', provides more information on this.

If I notice a problem, what should I do?

It is important that you are aware of the symptoms associated with lung problems, such as cough, shortness of breath or fatigue, and that you see your doctor about them as soon as possible.

When you visit the doctor, you may be asked to take a spirometry test. This tests your breathing and can help in the diagnosis of lung problems. You will be asked to breathe into a device that measures the amount of air in your lungs and how fast you can breathe out. Our spirometry factsheet provides more information on the test. You may also be asked to take an exercise test to measure your limitations.

Exercising with a long-term lung condition

People with long-term lung conditions can help improve their symptoms through regular exercise.

If you have a long-term lung condition, the thought of becoming quickly out of breath can be daunting and you may not feel motivated to exercise. It can be tempting to avoid exercise because you think it will make you breathless, but if you do less activity you become less fit and daily activities will become even harder.

It is best to ask the guidance of a doctor or physiotherapist before you begin exercising, to ensure that your exercise plans are in line with your capacity and are safe. All exercise programmes must be built up over time to allow the body to adapt. It's important that you exercise at your own pace. If you reach a stage where you are too breathless to talk, then slow down the pace or if necessary take a short pause. The more you do, the more you will be able to do!

Intermittent exercises can also help you to deal with the shortness of breath. In this case you alternate brief exercise, lasting 1-2 minutes, with moments of rest (or slower exercise). This is called 'interval training'.

COPD

If you have COPD, you will have damaged airways. This means that when you breathe out your airways become narrowed before you have got rid of all the air in your lungs. Many people with COPD find that pursing their lips enables them to breathe out more slowly and effectively. You may also find it easier to walk with braced arms (for example leaning on a shopping stroller, or even by grasping the belt of your trousers). Patients with severe lung disease can benefit from using a wheeled walking aid.

If you suffer from severe COPD, you may have problems bringing enough oxygen into the body. If this is the case, you may need to take supplementary oxygen during your activity. Your doctor will be able to assess this before you begin a training programme.

Read factsheet on 'Living an active life with COPD' for more information on how to stay active with COPD.

Lung fibrosis

If you suffer from lung fibrosis, interstitial lung diseases or problems with the chest wall, you will have difficulties expanding your lungs. You may need to breathe in more deeply and slowly, to allow the lungs to expand as much as possible.

Asthma

Having asthma should not restrict your ability to exercise or be physically active. If you feel uncomfortable during or after exercise, you should ask your doctor to investigate whether the management of your condition could be improved. In fact, many athletes have asthma and are able to compete at the highest level when their condition is well-controlled.

Your doctor may prescribe medicine to control your symptoms. Inhaled steroids, a common type of drug used by people with asthma, are the most important controller medication you can take. β2 agonists are the best medication to give quick short term relief from symptoms.

If you are an athlete hoping to take part in competitions, you should check whether your medication is listed as a performance-enhancing drug. Most asthma drugs (including inhaled steroids) have no restrictions, but it important to check each drug you are planning to take. By receiving the best treatment, as early as possible, you will have the best chance of competing on equal terms with non-asthmatic competitors.

Case study: Kjeld Hansen, Denmark, has asthma and completed the New York marathon.

"It is hard to motivate yourself to train when your 100% is no match for a non-asthmatic person. My asthma sometimes felt as if I was breathing through a whistle. If you try to run and whistle at the same time, you'll feel what I felt."

"During training for the marathon, I felt my confidence grow. I followed my treatment regime carefully and exercised at least 3 times a week. By following my treatment plan, I was able to get rid of my asthma symptoms. The marathon training also felt amazing - I was able to push myself to new levels and see improvements day-by-day."

General tips

At the start of your work-out, prepare yourself with gentle activities involving the muscles you will be using duing your exercise (warm up)

Improve your flexibility with stretching exercises

Gradually improve your ability to exercise for longer periods (build up stamina)

Increase activity at your own pace, and do not be afraid to get modestly out of breath (i.e. 4-5 on a scale of 0-10)

Improve your muscle strength (i.e. by lifting weights)

At the end of your work-out, slow down your activities and stretch the muscles you have used and allow your breathing to return to normal (cool down)

Remember: Exercise can bring many benefits and be enjoyable, even with a long-term health problem. Even if a task seems difficult at first, if you tackle one thing at a time at your own pace, you will quickly notice an improvement in your symptoms.

# data[].attributes.attachment_link.description
This factsheet explains how exercise affects the lungs, how breathing is influenced by activity and the benefits of exercise for people with and without a lung condition. Regular physical activity and exercise improves quality of life, whether you are healthy or you have a lung condition.

# data[].attributes.attachment_link.readable_text
"One 60-minute run can add 7 hours to your life" claimed The Times last week. The story was based on a new review in Progress in Cardiovascular Diseases that concluded that runners live, on average, three years longer than non-runners and that running will do more for your longevity than any other form of exercise. But there's more to running than its health-enhancing effects. Research published in recent years has shown that donning your trainers and pounding the hills or pavements changes your brain and mind in some intriguing ways, from increasing connectivity between key functional hubs, to helping you regulate your emotions. The precise effects sometimes vary according to whether you engage in intense sprints or long-distance running. Here, to coincide with a new feature article in The Psychologist - " Minds run free " - we provide a handy digest of the ways that running changes your mind and brain.

Running changes your brain wiring
David Raichlen and his colleagues scanned the brains of young, competitive distance runners and controls while they rested in a scanner with their eyes open for six minutes. As reported in Frontiers in Human Neuroscience, the runners showed greater connectivity between the so-called frontal parietal network and other neural regions involved in working memory and self-control, which the researchers interpreted as likely due to the cognitive demands of running and the runners' increased aerobic fitness. The runners also showed greater "anti-correlation" between their default mode network (the DMN, which sparks into life when we're resting) and a series of regions involved in motor control and sensation - the researchers said this could indicate that when on the move, the runners are likely to be very cognitively engaged, with their DMN suppressed.

Intense sprints seem to boost your executive function
For a study published last year in Preventive Medicine Reports, researchers asked young volunteers (average age 12) to complete several 10-second sprints for ten minutes and then take some cognitive tests. The participants acted as their own controls and on another day (either before or after the sprint day) they completed the same mental tests after 10 minutes of rest. The participants' performance on the Stroop Test - a long-established measure of mental control or what psychologists call "executive function" - seemed to be enhanced immediately after the sprints and 45 minutes afterwards, as compared with after resting. There were no effects of the sprints on visual-spatial memory performance or basic mental speed (as judged by the Digit Symbol Substitution test). Based on their finding of an apparent benefit of sprints on executive function, Simon Cooper and his colleagues said there was a case for including more opportunities for intense exercise in the school day.

Seven weeks of interval running training can boost your cognitive flexibility
For three times per week for seven weeks, a small group of young dinghy sailors spent 45 minutes per session, rising to 90 minutes at the end of the programme, engaged in interval training: running fast for between 200 to 1000m, interspersed with periods of rest. The researchers tested their volunteers' cognitive function before the training period and afterwards, and compared the outcomes with a control group of young dinghy sailors who just continued their active lifestyle as usual. Writing in The Journal of Strength and Conditioning Research, Tomas Venckunas and his colleagues reported that the running group didn't just get fitter and better at running, but also showed superior gains in their cognitive flexibility: that is, they were better at adapting to rapid switches in task instructions in a keypress task on a computer.

Ridiculously extreme long-distance running shrinks your brain (but it grows back)
In 2009, 67 endurance athletes ran nearly 3,000 miles over 64 days, without a single day's rest, to complete the TransEurope-FootRace ultramarathon. For a paper in BMC Medicine, a team of researchers led by Wolfgang Freund scanned the brains of a sample of these runners before the race, during and eight months afterwards. During the race, the runners' brains shrunk, in terms of grey matter volume, by about six per cent, an amount that the researchers described as "substantial" considering that normal aging is associated with volume loss of around 0.2 per cent per year. However, at the final scan, the runners' brains had recovered to their pre-race volume. In a follow-up study in BMC Sports Science, Medicine and Rehabilitation, the same research team pinpointed the running-related grey matter loss to four key areas, including parts of: temporoparietal cortex, occipitotemporal cortex, anterior cingulate and prefrontal cortex, and caudate nucleus. Although highly speculative, they noted the overlap of these areas with the Default Mode Network and suggested the observed cell loss in these regions may reflect the combination of the metabolic demands of running combined with a prolonged lack of use of the DMN, the brain's resting-state network.

The "runners' high" may be linked to changes in brain chemicals
Completing a run can leave you feeling euphoric and several studies suggest this could be down to changes to the brain's chemical messengers. For instance, a 2008 study in Cerebral Cortex used PET neuroimaging to show that a two-hour run led to enhanced opioid binding across several areas of the brain, as compared with before the run, and that this was associated with subjective feelings of euphoria. This supports the idea that running triggers the increased released of endorphins in the brain - a kind of natural high. A more recent paper in the Journal of Experimental Biology pointed to the importance of other neurotransmitters: the researchers found that an intense treadmill run, but not a walk, was associated with increased circulation of endocannabinoids - endogenous brain chemicals that bind to the same receptors in the brain as cannabis.

Running may quieten your mind
Anecdotally, many runners also say that going for a jog has a calming effect, helping their brains dial back on usual levels of worry and rumination. A study published last year in Experimental Brain Research appeared to provide some partial scientific support for this idea. Petra Wollseiffen and her colleagues used electroencephalography (EEG) to measure the surface electrical activity of the brains of 11 ultramarathoners several times during a six hour run. Running was associated with reductions in activity in the frontal cortex of the brain, and for the first hour, runners also reported feeling more relaxed and an increased sense of "flow". However, the levels of decreased brain activity and subjective feelings of flow didn't correlate so it would be an oversimplification to say that this research shows that running helps you to relax by switching off your brain.

Running increases the growth of new neurons (at least in mice)
It was the received wisdom through most of the last century that adults can't grow new neurons - a process called neurogenesis. It's now known that this isn't true: in fact, new neurons continue to grow through life in specific areas of the brain. Interest has turned to the function of these news neurons and ways to encourage their growth. To date, much of the research is on rats and mice, in whom a recurring finding is that running seems to encourage neurogenesis. Take a seminal paper published in Nature in 1999. Fred Gage and his team reported that mice who had the opportunity to choose to run in a spinning wheel exhibited twice the amount of neurogenesis in a part of the hippocampus (a brain region involved in memory and learning), as compared with mice who had no choice but to swim or others who had to complete a water maze. More recent animal research suggests that it is particularly long-distance running, as opposed to interval-style training (short bursts of running) that may increase neurogenesis, perhaps through release of what's known as "brain derived neurotrophic factor (BDNF)", a chemical that encourages cell growth.

A short jog may help you regulate your emotions
For a 2015 study in Cognition and Emotion, Emily Bernstein and Richard McNally asked volunteers to jog or stretch for 30 minutes and then they showed them a sad clip from the film The Champ. Participants who said they usually struggled to handle negative emotion were more intensely affected by the sad clip, just as you'd expect, but crucially this was less so if they had completed the jog (but not the stretching). The researchers said: "... a bout of moderate aerobic exercise appears to have helped those participants potentially more vulnerable to problematic affective dysregulation to be less susceptible to the impact or lingering effects of the stressor".

Intense sprints may boost your ability to learn
Bernward Winter and his colleagues tested participants' ability to learn new made-up words for objects after either two intense sprints of three-minutes length, after 40 minutes of gentle running, or after resting. Participants were able to learn 20 per cent faster after the sprints compared with the other conditions, and they showed superior memory retention when tested again a week later. Writing in the Neurobiology of Learning and Memory, the researchers said the blood measures they took suggested that the participants' enhanced learning performance after sprints may have been associated with increased levels of dopamine, epinephrine, norepinephrine and BDNF. "This [finding] is pertinent to the organization of learning-supportive environments, e.g., in schools (intense exercise during the breaks)," the researchers said.

Running a marathon seems to wipe your memory of the pain
Let's not romanticise long-distance running. As Daniel Engber observed at Slate last year, "a vast, disturbing literature has now accumulated on the ill effects of running marathons", particularly all the pain, including chaffing, blisters and cramps. One way that repeat marathon runners seem to cope is that the satisfaction of completing a run gradually wipes their memories for the pain they went through. Researchers demonstrated this for a study published in Memory: they asked marathon runners to report their pain and emotions directly after completing a marathon and then caught up with them again six months later, to ask them to recall their earlier post-marathon pain. The runners tended to have forgotten just how much pain they'd been in, and this was especially true if they'd been on an emotional high at the end of the marathon.

-Want to read more about the psychology of running? Check out this month's cover feature at The Psychologist about psychologists who run and whether their experiences match the data: Minds run free.

-Image via Giphy.com

# data[].attributes.attachment_link.title
10 Ways That Running Changes Your Mind and Brain

# data[].attributes.attachment_link.description
When you go for a run, it's not just your body that gets a workout. By Christian Jarrett

# data[].attributes.attachment_link.description
In endurance sports such as cycling and running, hitting the wall or the bonk is a condition of sudden fatigue and loss of energy which is caused by the depletion of glycogen stores in the liver and muscles. Milder instances can be remedied by brief rest and the ingestion of food or drinks containing carbohydrates.

# data[].attributes.attachment_link.readable_text
Beth asks: I'm considering training for my first marathon, but I'm intimidated by the longer miles. More specifically, I'm terrified of hitting "the wall." Any suggestions for me to get past this sticking point?
Our fears are usually far worse than reality. Instead, embrace your fear by turning it into curiosity. If you really want to run a marathon, jump into training with both feet.

Not everyone who runs a marathon will "hit the wall." There are many factors that contribute to this phenomenon, and some are within your control while some may not be. Researchers suspect it is likely that genetics plays some role in this, and your daily diet may also be a factor.

In general, hitting the wall refers to depleting your stored glycogen and the feelings of fatigue and negativity that typically accompany it. Glycogen is carbohydrate that is stored in our muscles and liver for energy. It is the easiest and most readily available fuel source to burn when exercising, so the body prefers it. When you run low on glycogen, even your brain wants to shut down activity as a preservation method, which leads to the negative thinking that comes along with hitting the wall.

It's important to note that you burn a blend of stored carbohydrate and fat for fuel all of the time. However, the ratio of these two fuels changes with the intensity of the activity. For example, during a speed workout you will use a higher percentage of glycogen in your fuel blend. On a long slow run, you would burn a higher percentage of fat and a lower percentage of carbohydrate.

If you do the math, it's easy to see why many runners hit the wall around the 18- or 20-mile mark. Our bodies store about 1,800 to 2,000 calories worth of glycogen in our muscles and liver. On average, we use about 100 calories per mile when running, depending upon run pace and body mass.

However, proper training for marathon mileage gives your body and mind time to adapt to these rigors. Since you don't use purely carbohydrate as fuel, you have the ability to continue running by accessing fat stores.

The energy issue then, is really about reaching for those fuel sources. In order to utilize your fat stores, you must have some carbohydrate present to facilitate this metabolic pathway. When you deplete your glycogen stores, it becomes difficult to access fat as a fuel source because burning fat for energy is a more complex process. Long runs help train your body to utilize the fat metabolic pathway more efficiently.

During training you should also experiment with taking nutrition on longer runs for a quick carbohydrate source. By the time you build up to 20 mile runs, you should have a pretty good idea about how much fuel you need to sustain yourself for this distance. ( Here are more tips to help you avoid hitting the wall.)

Hitting the wall is not something that needs to be feared, dreaded, or avoided (unless it's race day, of course). The old adage of "if you don't use it, you lose it" can be applied here.

Training is more than just logging the miles. It is a total body process, and by the end of it you will be transformed into a runner that is prepared and ready to meet all the demands of the marathon. Between stored glycogen and stored fat, you actually have the ability to run many, many miles.

# data[].attributes.attachment_link.description
Beth asks: I'm considering training for my first marathon, but I'm intimidated by the longer miles. More specifically, I'm terrified of hitting "the wall." Any suggestions for me to get past this sticking point? Our fears are usually far worse than reality. Instead, embrace your fear by turning it into curiosity.

# data[].attributes.body
The hormones that are involved in runner's high also can be found in marijuana buzz. Running causes the release of many hormones.

# data[].attributes.body
Running causes lactic acid build up in your muscles and can improve parts of your body such as your heart and lungs. More running makes you stronger and can also hurt your legs.

# data[].attributes.body
Running also causes many injuries such as muscles and bones. It is very easy to get stress fractures (when you get tiny fractures in your bone by putting too much pressure on your bones (such as running too much too fast when you aren't in shape))

# data[].attributes.body
When you hit the wall, your glycogen stores in your legs run out because you have been running for a long time. This causes your legs to start to feel terrible and you loose energy.