In Chemistry, Time and Chronic Disease article, we followed what happened when living tissues remain exposed to chemistry over time. Because food brings chemical matter into the body, we concluded that another issue worth exploring in chronic disease is “what this accumulated chemical history may eventually mean for the physical organization and mechanical behavior of living tissue.” Life requires continuous chemistry, but that chemistry takes place in living tissues that age, repair and change over time.
Nutrition, physical activity and other health practices can influence how well those materials are maintained and may alter the pace of some age-related changes, but when it comes to longevity, none makes chronological time run backward. A heart that has worked for eighty years, along with the arteries, lungs and kidneys, carries eighty years of biological history shaped by chemical exposure, use, repair and remodeling. Tissues are therefore not merely places where chemistry occurs. They are also the physical materials from which our organs are constructed.
Within the circulatory system, blood vessels must physically expand with each pulse and recoil as flow continues, while the heart must fill, change shape, generate force and relax. The lungs must repeatedly expand and recoil as air moves in and out, while the kidneys must preserve an extraordinarily delicate filtration structure as blood continuously passes through them under pressure. Except for the obvious actions of skeletal muscle, we do not always describe these organ activities as movement because most occur beyond our awareness.
But when we say that an organ is a physical structure, what is the living material that gives it its physical properties? Cells do not simply sit next to one another. They live within an organized extracellular environment containing water, collagen, other proteins, carbohydrates and numerous molecules that together form what is broadly called the extracellular matrix. Cells and this surrounding matrix form organized living tissues, while the matrix helps support the arrangement of cells and contributes to how tissues hold their shape, transmit force, stretch, recoil and respond when pressure or other mechanical demands are imposed upon them. Different organs contain different cells and differently organized matrices because the physical work required of an artery, heart, lung, kidney or skeletal muscle is not the same.
The composition and organization of the extracellular matrix can also change. Persistent injury and repair can produce fibrosis, in which excessive matrix material alters normal tissue architecture, while calcification can still introduce different material properties. These are molecular and structural events, but they also raise physical questions. What happens to a tissue containing increasingly cross-linked collagen? What happens when fibrosis develops in an organ that must stretch or recoil?
The consequences depend upon the tissue and the extent and location of the change, but the general principle is straightforward. Increasing collagen cross-linking or fibrosis can make tissue less compliant, so that more force or pressure may be required to stretch or deform tissue that once accommodated those demands more easily. A structure that normally stretches and recoils may become less able to do so, while changes in the extracellular matrix can alter how forces are transmitted between cells and across the tissue. Because cells are physically attached to and influenced by their surrounding matrix, changing that matrix also changes part of the mechanical environment the cells themselves experience.
We can describe blood pressure numerically, but the pressure represented by that number ultimately acts upon physical material. A relatively compliant artery and a stiffer artery may encounter the same pressure but cannot necessarily accommodate it in the same way. Elastin, collagen, calcification, inflammation, glycation and other forms of remodeling can alter the material properties of the arterial wall over time. The heartbeat still arrives, but the material receiving that pulse may no longer stretch and recoil as it once did.
Heart function is often measured through heart rate, rhythm, blood pressure, ejection fraction and electrical activity, but beneath those measurements is living material performing physical work. When scar formation, fibrosis, altered collagen organization or other forms of remodeling change that architectural environment, the heart is still asked to perform the same fundamental tasks through material whose properties have changed.
Kidney disease is often encountered through estimated filtration rate and other laboratory measurements, but filtration occurs across microscopic physical structures exposed continuously to blood flow and pressure. The glomerular filtration apparatus depends upon an extraordinarily organized relationship among cells, membranes, matrix and capillaries. Changes such as thickening, matrix expansion, scarring and fibrosis can therefore alter the architecture through which filtration must continue. The laboratory number tells us that function has changed, but the reality is that the function had to be produced by a physical structure in the first place.
Even electrical physiology cannot entirely escape this physical reality. Atrial fibrillation, a common abnormal heart rhythm, is an electrical disorder, but electrical impulses travel through living cells arranged within physical tissue. Fibrosis, scarring and structural remodeling can alter that landscape and influence how electrical activity travels through it, although these changes are neither the only causes of atrial fibrillation nor sufficient to explain every case. The specialized cells of the heart’s conduction system are themselves living tissue, and aging, injury, fibrosis and disease can interfere with impulse generation or transmission. Electrical activity ultimately coordinates another physical event as heart tissue contracts to move blood.
It is therefore clear that cells and tissues live in both chemical and mechanical environments. Cells do not only respond to nutrients, hormones and other chemical signals. They can also sense when their physical environment changes and respond by changing their own activity, including how they maintain and remodel the tissue around them.
Physical activity becomes the focal point here, not because the phrase “exercise is medicine” needs another slogan, but because moving an entire human changes both the metabolic and mechanical environment of the organism. A person sitting quietly is not metabolically or mechanically inactive, but physical activity increases metabolic demand while also changing the forces, pressures, flows and movements experienced throughout the body. Working muscles require more energy, prompting circulation and ventilation to adjust to the increased demand while tissues throughout the body experience mechanical conditions different from those experienced during inactivity.
Movement changes the range, magnitude, frequency and distribution of mechanical events already occurring within the body, repeatedly asking living tissues to operate across a broader physiological range than prolonged physical inactivity usually requires. This does not mean that every mechanical stimulus is beneficial or that more loading is always better. Excessive pressure can damage vessels, excessive loading can injure musculoskeletal tissues, and compromised tissues may tolerate demands very differently from healthy ones.
Regular physical activity cannot guarantee that tissues will remain healthy, nor can movement simply reverse fibrosis, calcification, scarring or other structural changes once they are established. What regular physical activity can do is repeatedly challenge living tissues in ways that help maintain their capacity to meet physical demands. When aging or disease has already changed those tissues, rehabilitation works with the capacity that remains, seeking to improve strength, mobility, endurance and tolerance for ordinary physical demands even when the underlying structural change cannot simply be removed.
Chemistry and time therefore remain inseparable, but following their consequences into living material reveals another dimension of health and chronic disease. Prevention is partly about preserving the physical capacity of living tissues, while rehabilitation is often about developing the capacity that remains. Alongside asking what changed chemically or what changed in a laboratory measurement, we should also ask what the tissue became physically and what the living system can still be helped to do. This is where regular physical activity finds its place, not simply because “exercise is medicine,” but because living tissues retain and develop capacity partly through being repeatedly required to use it. The slogan may be convenient, but the biology underneath it is far more interesting than it sounds.
Mukaila Kareem is a doctor of physiotherapy and founder of metabolichealthliteracy.com
