Limits of Cellular Regeneration Underpin Lifespan

Seth Nickerson, Staff Writer

The human body contains trillions of individual cells, each representing the most basic unit of life, and comprising hundreds of unique cell-types. Our cells perform thousands of distinct functions, such as fighting infection, secreting insulin, or sensing the environment. Together, they form productive ensembles of various cell types that constitute the dozens of specialized organs within us.

These multicellular organ structures carry out the complex biochemistry of life. However, the byproducts of their metabolism can be toxic and capable of causing mutations in our DNA which, if left unchecked, can accumulate and initiate the formation of cancer. Our defense against this damage is the immune system, which eliminates such precancerous cells, and then monitors their replacement by inducing the proliferation of undamaged neighboring cells.

This is the case for many organs and cell types but not all, the remainder of which lack robust proliferative capacity and, rather than divide or die, must continuously repair their damage. Such cells are found within organs such as our brains and our hearts, and once lost, are virtually impossible to replace. These static cells compose tissues and organs that are essential for survival, and in a sense, represent the limits of an organism’s lifespan.

The contractile muscle cells of the heart, called cardiomyocytes, are one such static cell type, the number of which is fixed shortly after birth. Chained together and pulsing in sync every second, they pump vital blood throughout the body. Yet a single heart attack can cut off the flow of oxygen to these cells causing their ineluctable destruction. Once lost, they are unlikely to regenerate. Without reconstruction, this cellular chain of muscle is weakened forever.

The neuronal cells of the brain form a massive, intricate, three-dimensional network that allows for the computation, transmission, and storage of information. Over time, these cells embody life experience and become intimately interwoven, yet in adulthood, they rarely divide or regenerate. These properties make neurons very precious, and each one exquisitely unique.

Destruction of neurons underlies the permanent memory and cognitive deficits that are common symptoms during the progression of Alzheimer’s disease. If lost neurons were able to regenerate, they might never replace what experience had woven over decades. The ability to reconstruct such elegant and convoluted structures is one of modern science’s most remarkable challenges.

Despite the inherent vulnerabilities of our hearts and our minds, our lives are completely dependent upon these organs. Yet the trauma of mere existence, the very concept of growing old, weakens our biological systems, and ultimately, they will expire or fail. The impermanence of life thus can be described as a narrative – the limitations and shifting balance of damage and regeneration on a cellular level over time.

Scientists strive to determine what is necessary and sufficient for a biological system to function. From that knowledge, we deduce what to fix and how to fix it when our bodies break or come under duress. Our aim is to develop such a complete understanding of the mechanics of life that we can enhance human health with alacrity.

This paradigm of research and development is the goal of basic medical science. Initially, we study the human condition until our knowledge of its mechanisms becomes exhaustive. Eventually, our ability to command human physiology will transcend the forces of nature.

Seth Nickerson is a PhD candidate in the department of Biochemistry and Molecular Pharmacology at the NYU School of Medicine. Contact him at: Seth.Nickerson@med.nyu.edu

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