A car with 200,000 miles that has been on the road for several years may have had its tires replaced three or four times. The short history of wear accumulated by the first set of tires left with those tires when they were replaced, while the engine, despite regular maintenance and the replacement of some of its components, has remained with the car through much more of its journey. The tires and the engine therefore belong to the same car and have traveled much of the same road, but they have not carried the same history of that journey.
The human body is not a machine, and living tissues possess capacities for repair, renewal and adaptation that make the comparison imperfect. That said, food brings chemical matter into contact with cells, tissues and organs throughout life, but those tissues do not necessarily carry the history of that chemistry for the same length of time.
Before food enters the circulation and its components become available to tissues elsewhere in the body, it must be digested, transformed and physically moved across biological surfaces. Among the earliest major cellular interfaces between what we consume, and the internal biology of the organism is the intestinal lining, whose cells repeatedly face the consequences of human eating behavior without having any say in what arrives.
The cells lining the intestine do not determine the size of the meal, when the next one arrives, or how long the same pattern of eating continues. It also does not matter to the cells whether we call the eating pattern high-fat and low-carbohydrate, Mediterranean, or low-fat and high-carbohydrate. They encounter, process and respond to whatever mixture of nutrients arrives.
Remarkably, many of the intestinal cells performing this work will be gone within a few days. New cells are continually produced, move along the intestinal lining, perform their functions, and are eventually shed and replaced by new ones. A person may maintain a particular pattern of eating for decades, and the intestine may repeatedly experience that pattern, but no individual intestinal lining cell remains there for anything close to that length of time.
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This creates a divergence between exposure and biological history. Chemistry occurs throughout the brief life of an intestinal epithelial cell, but because the cell is quickly removed and replaced, the chemical history it carries is also relatively brief. The exposure may therefore persist at the level of the person and the organ even as the cells experiencing it are continually replaced.
A mature red blood cell provides a useful comparison because it circulates for roughly 120 days, considerably longer than the few days of an intestinal lining cell. During those three to four months, red blood cells repeatedly encounter the chemistry of the blood, with one consequence familiar in clinical medicine through what we call hemoglobin A1C.
As glucose circulates, some of it reacts spontaneously with hemoglobin, a process called glycation. The extent of that glycation reflects both glucose exposure and time, which is why hemoglobin A1C provides a useful record of glucose exposure over the last few months. A newly formed red blood cell has not experienced the same circulating history as one approaching the end of its lifespan.
The red blood cell therefore provides a readily measurable chemical history extending across months. That history also has an endpoint because red blood cells are continually removed and replaced. The population carrying today’s A1C record will eventually disappear, while another population begins writing the next one.
Importantly, some cells can remain within the body for many years and some for a lifetime. Many nerve cells in the brain, spinal cord and peripheral nerves can persist for decades, while collagen and other components of the extracellular matrix form part of the structural framework of tissues throughout the body, including blood vessels, the heart, kidneys, skin, tendons and bones. Their persistence gives chemistry a much longer period in which repeated exposure, modification, repair and renewal can interact.
This long history becomes clinically relevant in what we call chronic diseases. Over time, disease can become clinically recognizable as diabetic neuropathy in the peripheral nerves, diabetic retinopathy in the eyes, and diabetic kidney disease that may eventually progress to chronic kidney disease. Across the cardiovascular system, changes occurring over time contribute to conditions such as atherosclerotic cardiovascular disease, while persistent hypertension places continuing demands on blood vessels and the heart.
These conditions cannot be explained by time, glycation or the longevity of cells and structural proteins alone. Genetics, metabolic conditions, tissue-specific characteristics and differences in maintenance and repair also influence what develops over time. This is where chemistry begins to carry a history that extends beyond the period captured by our laboratory measurements.
Living tissues do not stop functioning while this chemistry unfolds. A kidney cannot stop filtering blood while its components undergo maintenance and repair, a heart cannot suspend blood pumping action while proteins and membranes are renewed, and peripheral nerves must continue maintaining their cellular architecture while conducting information. Maintenance is therefore part of living, not an interruption from it.
Chemical modifications occurring within these tissues may be repaired, altered molecules may be degraded and replaced, and damaged components may be removed. What cannot be completely repaired, replaced or cleared may become part of the biological history within which subsequent metabolism continues. In this sense, time gives chemistry the opportunity to become biological history.
This is especially relevant to food because nutrients repeatedly enter an organism that is already metabolizing. Glucose, fatty acids and amino acids are therefore not entering a passive, empty container during consumption. Each meal brings new chemistry into tissues that already carry a biological history.
That history makes the word chronic meaningful biologically. A metabolic disturbance lasting several hours is not equivalent to similar disturbances recurring over many years. One unusually high glucose concentration does not produce diabetic neuropathy, one meal does not produce chronic kidney disease, and one day of metabolic excess does not create diabetic retinopathy or cardiovascular disease. These conditions have complex and disease-specific causes, but they develop within tissues whose biology has been unfolding over long periods of time.
Clinical medicine gives us an interesting window into this difference in timescale. A home blood glucose measurement tells us about glucose at that particular time, while A1C provides a useful record extending across the preceding months. Yet the chronic complications we monitor, and treat may have been developing within tissues over years or decades. Improving glucose control changes the metabolic environment those tissues encounter going forward, but it does not make their previous biological history disappear.
This may be one reason chronic disease cannot be understood entirely from a snapshot of the present. The laboratory measurement is current, while the tissue has a past. That past is not destiny because living tissues continue to repair, replace, remodel and adapt, and treatment can alter what happens next. Biology does not start from zero each morning. What happens within tissues today is partly shaped by what they have already experienced and by what they were able to repair, replace or carry forward.
Chemistry therefore cannot be separated from time when we think about chronic disease. The reactions themselves may occur in moments, but their biological consequences unfold within tissues that must continue functioning while repair, renewal and replacement occur along the way.
What this accumulated history may eventually mean for the physical organization and mechanical behavior of living tissue is another question. The important point here is that the interaction between chemistry and time does not leave the same history in every tissue. These differences are among the reasons why chronic diseases such as diabetes, hypertension, cardiovascular disease and kidney disease must be managed not only in the present, but across time.
Mukaila Kareem is a doctor of physiotherapy and founder of metabolichealthliteracy.com
