Aging At The Down Of Precision Medicine

Admin Learning 8 months ago

The idea is to die young as late as possible.

-Ashley Montagu, Anthropologist

Historically, biological sciences have been treated as soft science- science that lacks rigorous mathematical modeling and therefore cannot predict outcomes precisely. This status of a largely observational science is about to change to a quantitative one with the advent of Systems Biology and other predictive approaches, with the potential to revolutionize the field of medicine.

The dominant method of studying biological systems so far has been the method called 'Reductionism', where a system is best described by its component parts. 'Reductionism' has been effective to describe physical systems with a level of certainty yielding concrete mathematical models like Newton's laws of motion and even Einsteins' General Theory of Relativity. But due to the inherent complexity of living organisms, biological sciences lack even a rudimentary mathematical model, rather widely relying on population parameters like mean values and ranges of values with 95% confidence intervals. Such measurements have served our purpose so far, but there is much to progress. Simply put, for biological sciences, we are not there yet. Here comes the role of Systems Biology. Based on the principles of 'Complex Adaptive Systems', Systems Biology aims to measure the various components as well as their interrelations, revealing a complete description and a set of mathematical formulas to predict their behaviors in a wide array of situations. But as biological systems have been shaped by millions of years of evolutions rendering a level of complexity the entirety of which is likely beyond single human comprehension, a non-axiomatic, non-hypothetical 'Biomarker' based 'Big ata' approach is likely to be the best way to go. This is exactly what 'Precision Medicine' is1.

Traditional medicine has been successful at treating simple ailments with pretty straightforward ontology. Precision medicine is likely to thrive uncovering and manipulating 'Complex Biological Traits', a collection of interrelated pathways and functions that were developed together in the way of evolution and the disturbance of which thus creates diverse systemic symptoms. Examples of such 'complex biological traits' are cancer and aging. While preventing and treating cancer is the first priority of 'Precision Medicine Initiative'6, it won't be much longer to adopt this approach to the problem of 'Aging'.

Preventing aging and gaining immortality have been the quest of humankind for long, prompting kings to appoint their sages in the quest of immortality elixirs and potions, but significant achievement came only in the twentieth century mainly through public health approaches. During this century, life expectancy in developed countries doubled. But this significant achievement is ascribed mainly to decreased childhood mortality. Moreover, the period of life living with relative health has increased significantly, but the maximum lifespan of humans as a species hasn't. This has lead to the hypothesis of 'Compression of Morbidity' stating "If the aging process was plastic, and thus modifiable, then decreasing health risks could delay the onset of morbidity and the morbid period could be squeezed between a delayed age at onset and a less delayed increase in age at death, decreasing lifetime morbidity and improving senior health"2.

Although aging and longevity has been used collectively in different contexts, these two confer significant differences. Aging is a stochastic process, while longevity in a species is evolutionarily conserved. This has led to two different approaches to address the problem of aging.

Aging is an inevitable process occurring through an immutable law of nature, the second law of thermodynamics. So we cannot stop aging, but we can try to slow its progression by adopting a different lifestyle. This has given rise to the popular anti aging techniques like Caloric Restriction, Antioxidant therapy etc. It is mostly related to the extrinsic rate of aging.5

On the other hand, Longevity in a species is evolutionarily conserved. It means that it is already written in their genome at what age a member of a species will mature sexually, and how much maximum lifespan an organism can achieve4. There is significant interspecies difference, so if we can identify a gene or pathway that leads to a species' long life, we can utilize that pathway or gene to increase maximum human lifespan. There is also intraspecies diversity, with some groups of humans living consistently longer lives (e.g. Japanese, Ashkenazi Jews). Close scrutiny of their genetic makeup can also reveal significant findings.

A third approach has been popularized recently ascribing aging to epigenetic changes. According to this school of thought, aging occurs due to accumulated genomic information loss, and epigenetic factors like Sirtuin have the capability to repair and maintain the integrity of the genome, thus slowing and even reversing the effects of aging3.

To implement these antiaging, longevity promoting techniques, we will need 'Precision medicine' to make decisions for individual person. Public health measures like caloric restriction, exercise can help achieve antiaging to some extent, but there is significant individual variation, so one prescription may not fit all. Moreover, there is differential organ aging, meaning different organs of an individual age at different rates7. So anti-aging intervention for one kind of 'organ-ager' may not be appropriate for another.

Adopting Precision Medicine will take more time, and technical problems to implementation will not be the only obstacles. And there is a growing consensus among scientists that humankind or at least some of them will become immortal -mortals with no maximum lifespan- within this century. Whether it becomes true or not, human healthspan and lifespan will almost certainly increase with effects on personal motivations, interpersonal relationships and even human fertility with radical consequences on our species as a whole8. So the ethical burden lies on our shoulders as to how to safely adopt and adapt these changes. 


Bibliography:

1. Mandana Hasanzad, Precision Medicine in Clinical Practice

2. James F. Fries, On the compression of morbidity: from 1980 to 2015; Handbook of the Biology of Aging 3. David A. Sinclair, Matthew D. LaPlante, Lifespan: Why We Age and Why We Don’t Have To

4. Xiaqing Zhao, Daniel E.L. Promislow, Senescence and Aging; The Oxford Handbook of Evolutionary Medicine

5. Roger B. McDonald, Biology of Aging

6. Precision Medicine Initiative (PMI) report by National Academy of Sciences (NAS), USA, Biomarker Tests for Molecular Targeted Therapies: Key to Unlocking Precision Medicine

7. Alessandro Ori et al, Cell Systems, volume 1, issue 3, Integrated transcriptome and proteome analyses reveal organ specific proteome deterioration in old rats

8. Yuval Noah Harari, Homo deus: A Brief History of Tomorrow 


Sk. Mehedi Hasan 

Dhaka Medical College