Our Bodies Were Not Built To Last

As summer kicks in to high gear, the weather is heating up, MLB pennant races are heating up, barbecue grills are heating up, and the music is reckless and hot. Last summer witnessed the 50^th anniversary of the Grateful Dead with an epic reunion and the 20^th anniversary of the passing of Jerry Garcia. Yet, unbelievably, the music never stopped and the long strange trip continues. The Dead have been resurrected once again, with Dead and Company rocking a six-week US tour. With my kids finally accepting their own fate as the next generation of Deadheads, the revival of the music that makes so many of us feel alive has gotten me thinking about heritability and what information (biological or existential) is critically important to pass on to the next generation. And further, what is the meaning of life? (Full disclosure: this could simply be how I am dealing with my own process of aging, so please humor me for a moment…)

 

Here’s a sobering thought: the fundamental meaning of life is to get your genetic material into the next generation. There is no deeper meaning from a biological perspective than to maximize reproductive fitness. Different species take different approaches to spreading their seed, so-to-speak. On one end of the spectrum, some animals like sockeye salmon and mosquitos, which live in relatively unstable environments where the probability of survival is relatively low, focus on producing large numbers of offspring before they die, hoping that these offspring will reach sexual maturity and also reproduce. This is a good reproductive strategy in such environments because reproductive fitness is defined not by one’s ability to pass on their own genes, but by their offspring’s ability to pass on their genes.

 

Contrast this with the approach at the other end of the spectrum. Some animals, like orcas and primates live in much more stable environments, in population densities that are near carrying capacity for the environment (the highest density that can be supported by the resources available). These species produce many fewer offspring, but because there is a high probability of survival for offspring and parents alike, the parents invest a considerable amount of energy into raising their offspring (I know this is true because my kids exhaust me! Please help…)

 

In the case of primates, in particular, we know a great deal about reproduction, life history, and parental investment: primates produce few offspring, invest considerable energy into offspring care, and they generally have lengthy lives relative to other species in the same habitats. Compound this with advances in modern medicine, and human primates are enjoying lifespans that increase with successive generations. We live longer than our grandparents’ generation, and so on and so forth. And while this is fantastic news because we get to enjoy our children and grandchildren for longer than at any other time during human history, this does not come without a significant price: our skeletons break down in ways that other primates’ do not. Simply put, our bodies were not built to last.

 

Humans are unique among primates in that we walk around on two legs. In fact, the evolution of our bipedal locomotion predated the evolution of our large brains by several million years. And our unique mode of locomotion combined with our ever-lengthening lifespans has resulted in several musculoskeletal problems that we develop as we age. Before we get to that somber topic, it is useful to review some of the anatomical adaptations that allow us to walk around bipedally.

1. Forward position of foramen magnum. The foramen magnum – or the opening in the skull through which the brain stem/spinal cord exit – is more anterior positioned in humans compared to other primates and mammals, which places the vertebral column directly underneath the skull as opposed to behind it as in quadrupedal animals.

2. S-shaped curvature of vertebral column. By moving the vertebral column directly underneath the skull, humans require an S-shaped spinal curvature (with cervical and lumbar lordoses and a thoracic kyphosis) in order to balance the head and torso over the pelvis.

3. Broad pelvis with laterally-flared iliac blades. The iliac blades of the human bony pelvis – the parts that stick out to the side – are rotated laterally and flare outward from the midline of the body. This positions the lesser gluteal musculature (gluteus medius and gluteus minimus) lateral to the hip joint, enabling these muscles to function as abductors of the thigh at the hip joint, and prevent excessive pelvic tilt to the unsupported side during the stance phase of bipedal gait. In nonhuman great apes, this musculature is positioned posteriorly and acts synergistically with the gluteus maximus to extend the thigh, not abduct it.



4. Oversized hip and knee joints. Joint loading in response to bipedal locomotion, as well as that reflective of body mass, is borne entirely through the joint surfaces of the lower limb in humans. Therefore, we evolved expanded articular surfaces compared to our great ape relatives, which reduces shear stress in the articular cartilage. The femoral condyles and tibial condyles of the human knee are also significantly flatter in lateral profile than in nonhuman apes, which further reduces shear stress in articular cartilage. Because articular cartilage is avascular and cannot actively repair itself, reducing the shear stress borne by the cartilage also reduces the incidence of damage.



Carrying angle of the femur

5. Carrying angle of femoral shaft. The shaft of the human femur (thigh bone) is oriented obliquely relative to the femoral condyles (the part of the femur that sits on the tibia, or leg bone, to form the knee joint). This angled shaft places the knee joint directly under the center of mass. In quadrupedal animals (including our great ape relatives), the femoral shaft is more vertically oriented.

6. Adducted hallux. The human hallux – or big toe – is in line with all other digits of the foot, enabling an efficient toe off in an anterior direction in bipedal gait. In nonhuman primates, the hallux is abducted, which enables these animals to grasp with their feet in a fashion similar to manual grasping.

7. Sesamoids in tendons of flexor hallucis brevis. Sesamoid bones are bones that develop in the tendons of muscles, and the best example is the patella, or knee cap. In humans, sesamoids also develop in the tendon of flexor hallucis brevis, a muscle in the sole of the foot that flexes the big toe. These sesamoids create a tunnel through which courses the tendon of flexor hallucis longus (another big toe flexor muscle). This tunnel allows flexor hallucis longus to remain free to contract and flex big toe when all of the body weight is placed on head of the 1st metatarsal, such as when pushing off during walking.

These seven adaptations to bipedal locomotion are present in the earliest members of the fossil genus Australopithecus (and some earlier ones too), even before brains evolved to be bigger. So one can make the argument that bipedal locomotion is the hallmark of human evolution, with the evolution of big brains being a secondary adaptation that may or may not be related to the evolution of our unique locmotor mode.

Numerous hypotheses exist as to why we evolved this weird form of walking. Walking around bipedally is energetically efficient; it requires only approximately 1 calorie/min to walk. Was this the advantage it proffered over quadrupedal locomotion? Or perhaps we became bipedal in order to free our hands up to carry provisions back to our mates. Or maybe it was a way of reducing heat stress by reducing the surface area where sunrays hit directly while increasing the amount of surface area exposed to wind? Could it have evolved in order for us to see over tall grasses in the savannah? Or to increase feeding efficiency and resource exploitation? Or perhaps it was so we could posture for mates… All of these are plausible hypotheses, and there are plenty of scientific arguments in favor or one or more of these. But the fact remains, it doesn’t really matter why we evolved bipedal locomotion. Any way you slice it, we evolved it. And now we’re saddled with the baggage of our ancestors: bodies adapted to bipedal locomotion take a severe beating. Again, our bodies, especially our skeletons, were not built to last.



Vertebral compression fracture

Bone is approximately 60% mineral (calcium and phosphate) and the other 40% is collagen and other proteins. We reach our peak bone mass at about 30 years of age, which means that the most responsive time for us to build bone mass is while we are young and growing. With age, everyone loses bone mass and density; we call this osteopenia, and it is normal. But when we lose an abnormal amount of bone mass, we can this osteoporosis. Osteoporosis is common, with about 54 million Americans suffering from this disease, and often results in bone fracture. The most prevalent osteoporotic fractures are vertebral compression fractures, where the loss of bone in the vertebral column results in fracture of the body of the vertebra itself. Humans and the other great apes have an equivalent amount of bone mineral and equal bone densities, but human vertebral bodies are enlarged to absorb more compressive shock during bipedal locomotion. Therefore, they have thinner walls of the vertebral body, which are at risk of collapsing with reduced bone mass and/or density, resulting in compression fracture. These types of fractures do not occur in nonhuman apes because they have thicker walls of their vertebrae than do humans, and because their spines are parallel to the ground, not perpendicular, so there is no axial compression of the vertebral column during locomotion.

Another result of repetitive compression loading of the spine that only humans suffer is degenerative disc disease. Intervertebral discs between each of the vertebrae of the spine are comprised of two tissue types: a central, jelly-like nucleus surrounded by a strong, fibrous ring that contains the nucleus. After repeated compression, the fibrous ring of the intervertebral disc can break down, leading to a posterior bulge that impinges upon peripheral nerves that exit the spinal cord (which runs through the canal in the posterior aspect of the vertebral column). Ergo, pinched nerves. These degenerated discs do not occur with high frequency in nonhuman apes, again as a result of their quadrupedal (and less destructive) mode of locomotion.

Degenerative disc disease

One final example of how our long lifespans are not in accord with the “lifespan” of our skeleton is degenerative joint disease and osteoarthritis. The ends of bones with joint spaces are covered in a thin layer of hyaline (articular) cartilage. Hyaline cartilage is avascular, meaning that it does not have its own blood supply, and it cannot actively repair itself if damaged. In order to protect against damage, joint surfaces (of the knee at least) become flatter as body size increases during growth. This is because as body mass increases, so does the transarticular load transmitted through joint surfaces (and hyaline cartilage covering them). This has the effect of reducing shear stresses that are experienced by the cartilage and limiting the capacity to damage the cartilage by growth alone. When the hyaline cartilage breaks down, the result is damage to the bone, pain, and joint swelling – osteoarthritis. The incidence of osteoarthritis in nonhuman great apes is dramatically lower than in humans, and is attributed to a combination of shorter lifespans in the wild and the lack of a destructive, bipedal mode of locomotion.

Given all of the ways that our skeletons break down during life, it is truly quite remarkable that 60-70 year old musicians such as the surviving members of the Grateful Dead are still able to shake it, shake it in the summer of 2016. So we should embrace it while we can keep on dancing, keeping in mind that while every cloud has a silver lining; in this case, every silver lining does have a touch of grey.

Contributed by: Jason Organ, PhD

Follow Jason on Twitter.

Jungers, W. (1988). Relative joint size and hominoid locomotor adaptations with implications for the evolution of hominid bipedalism Journal of Human Evolution, 17 (1-2), 247-265 DOI: 10.1016/0047-2484(88)90056-5


Jurmain R (2000). Degenerative joint disease in African great apes: an evolutionary perspective. Journal of human evolution, 39 (2), 185-203 PMID: 10968928


Latimer B (2005). The perils of being bipedal. Annals of biomedical engineering, 33 (1), 3-6 PMID: 15709701


Russo, G., & Kirk, E. (2013). Foramen magnum position in bipedal mammals Journal of Human Evolution, 65 (5), 656-670 DOI: 10.1016/j.jhevol.2013.07.007


Ward, C. (2002). Interpreting the posture and locomotion ofAustralopithecus afarensis: Where do we stand? American Journal of Physical Anthropology, 119 (S35), 185-215 DOI: 10.1002/ajpa.10185

Coronary Artery Disease: A Role For Calcium?

In the heart, there still lie a myriad of mysteries. For everything we know about this integral organ, there are still several things we have yet to figure out. One of the most pressing questions is what factors are “at the heart” of the current coronary artery disease (CAD) epidemic and how can we stop it? It turns out that the answer, while still not fully understood, may have to do with a familiar element. Calcium, the mineral we all know from the milk commercials that is touted for healthy bones and teeth, may play a prominent role in keeping your heart healthy as well.

Anyone who has watched a medical show, from Grey’s Anatomy to Scrubs, will recognize this predictable scene in the hospital:  “Clear!” A flat line appears on a black screen, accompanied by a caustic continuous siren, blaring uproariously. The paddles that conduct electricity failed to restart the heart. “Clear!” The handsome doctor shouts once more after a dramatic pause. This time, the flat line turns into a rhythm and the continuous alarm morphs into a dulcet beeping, indicating the patient will live. Television often portrays the cure all for fixing the heart is simply a little electrical jolt from a defibrillator, easy as that.

The doctor will see you now!

             



Do not try this at home!

The heart is profoundly affected by electricity. Electrocution is an effective method for execution because sending large currents through the heart can render it useless. At the very least, a small shock can definitely cause your heart to skip a beat (just ask the little brother who stuck a butter knife into a power socket!). Electricity is so essential to the heart, the organ has evolved its own conducting system, which means it can regulate its own beat without input from the brain.

 

 

Many ailments can cause a heart to stop, but one disease is wreaking havoc on the human population and killing people in unprecedented numbers. As recently as 2013, coronary artery disease (CAD) has reigned supreme as the most common cause of death worldwide. As many as eight million people a year die from complications caused by CAD. Like cancer, it would be hard to find a person who doesn’t know someone that has been afflicted with CAD. Despite the steep number of people affected by the disease, there is little consensus on what causes this deadly condition or how to stop it.

The theories are numerous and some are understandably more credible than others. Coronary artery disease is thought to have a direct correlation with diet and exercise - most people diagnosed with CAD are obese and sedentary. And indeed, changing your diet, cutting cholesterol, quitting smoking, and beginning a healthy exercise regime does lower the incidence of CAD-related adverse events such as heart attack or sudden coronary death (which is exactly what it sounds like). But that isn’t the whole story, not by a long shot.



It is a difficult decision, but as they say,
"an apple a day keeps the doctor away". www.cdc.gov 

For a clearer view of what is really happening to the heart when it suffers from CAD we need to take a closer look - we need to look at the individual cells in the heart. There are several important players at this level, but the cells that reside in the large middle layer have been shown to play a significant role. This layer is made-up of cardiovascular smooth muscle (CSM) cells and these cells are thought to be the main players in the propagation of CAD.

In a healthy heart, the CSM cells are quiescent, that is to say they are stable, just hanging out and not doing too much. In a heart affected by CAD, however, the CSM cells come to life - they begin to divide and travel. When the CSM cells begin to divide and conquer, things start to go south because the simple act of proliferating and moving causes inflammation below the skin layer of the blood vessel. Like a cut on your finger, the injury causes inflammation and alerts the immune system, which will come to the rescue, close the cut, stave off infection, and save the day! The immune system’s army of white blood cells wants to save the day in the heart vessels as well and, while its intentions are good, the results can ultimately be disastrous. Why? After the work is done by the white blood cells, they leave what can be likened to a “scab” on your blood vessel. This thickening on the wall of the vessel can elicit additional responses from the immune system, thereby compounding the problem and causing the scab-like mound to grow and grow, possibly blocking off the entire blood vessel. When this occurs, it is referred to as a myocardial infarction (heart attack). The blood that supplies your heart is cut off, and the oxygen the heart needs to pump never arrives. When the heart can’t feed itself with oxygen, it certainly can’t send any to the rest of the body!

A clog, even in a small artery, can cause big problem
for your heart and your health. www.cdc.gov

But why do the normally passive CSM cells start to act out and move around? That is the million-dollar question. As mentioned above, the electrical signals in the heart are critical for the coordinated, rhythmic beating of the heart. The constant and familiar lub-dub of the heart is the result of a myriad of events occurring in perfect harmony. Perhaps just as important as the electrical current, however, are the affects it elicits, namely the release of the well-known mineral, calcium.

In addition to being pivotal for healthy bones, calcium is also a crucial player in achieving those perfectly rhythmic heartbeats. Calcium might even explain how the smooth muscle in your heart switches from innocent bystander to mischievous villain. The calcium in the heart acts a second messenger for CSM excitation-contraction (beating) and sends the signals that modulate CSM proliferation, migration, and calcification.

The blue dots represent calcium. When the heart behaves normally, the calcium remains constant and the cells of the heart do not divide. If excess calcium is allowed to build up in the sarcoplasmic reticulum (SR), however, the cells of the heart begin to divide and move. Eventually, the vessel wall becomes so large it is difficult for blood to pass. (modified from McKenney-Drake, Rodenbeck, at el., Atherosclerosis, 20

In order for the heart to beat properly, calcium levels must be precisely balanced with the help of channels or transporters, which regulate the flow of calcium ions in or out of cells. It seems likely that when calcium transporters break down, the mismanagement of calcium will cause problems in the heart. In mild CAD, certain avenues available to calcium transport malfunction, which causes the calcium to aggregate in the sarcoplasmic reticulum (SR, the compartment in the heart cells that stores calcium). When this happens, it essentially “activates” the proliferation of CSM cells. Dr. Dineen-Rodenbeck recently verified this hypothesis by blocking a common transporter that is responsible for bringing calcium back into the SR. When calcium is unable to aggregate in the SR, the cells are not switched “on” and all remained quiet. Once CAD becomes severe, the SR stores are basically depleted and the risk of death caused by complications associated with CAD rise. This is an important discovery because knowing the role of calcium in the heart and understanding what occurs when it is lowered or elevated may lead to treatments. In the end, the regulation of calcium may be the key to managing the CAD epidemic.

These studies should not be taken as proof that you need to regulate your dietary calcium differently – after all, calcium is essential for strong bones and teeth. Rather, these findings will help guide future research and treatment efforts that may be able to manage calcium levels specifically in the heart to alleviate CAD.

Contributed by:  April Barnard

 

References

Rodenbeck SD, Barnard AL, and Sturek M. SERCA inhibition attenuates medial thickening in an organ culture model of coronary artery disease. FASEB J (In Press).

Dineen SL, McKenney ML, Bell LN , et al. Metabolic syndrome abolishes glucagon-like peptide 1 receptor agonist stimulation of SERCA in coronary smooth muscle. Diabetes 2015; 64:3321–3327

 

Sturek M. Ca2+ regulatory mechanisms of exercise protection against coronary artery disease in metabolic syndrome and diabetes. J Appl Physiol. 2011;111:573-586.