Fight Aging!

The hypothesis that aging is a genetic program that is to some degree selected has always been a vocal minority view in the research community. There are just as many quite diverse theories of programmed aging as there are more mainstream evolutionary theories of aging that orbit the concept of antagonistic pleiotropy, the idea that lesser selection pressure in late life, because early reproduction means greater evolutionary fitness, allows for the evolution of mechanisms that are beneficial in youth and harmful in late life. There is even a fusion of the two sides: the hyperfunction theory of programmed aging suggests that aging is a consequence of developmental processes that fail to shut down.

One modern way of framing programmed aging is to consider the operations of cellular biochemistry derived from the genome as analogous to computer software, and aging the consequence of flaws in that software. If such software was evolved rather than designed, as some software is these days. That said, it is important to note that calling, say, the ability of a biological system to accumulate a specific form of damage and dysfunction a flaw (or a bug, or some other appropriate term for software that isn't behaving as desired) says nothing of how hard it might be to produce a better version that lacks this flaw.

It seems self-evident that at some point in the future our not entirely biological descendants, possessing some system for specifying the seed of an individual that is derived from or incorporating DNA, will be engineered to be functionally immortal. Immortal lower animals exist, such as the hydra that is essentially a steady state embryo, an ambulatory bundle of stem cells. Reconciling (a) the necessary mechanisms of constant growth, repair, and replacement to sustain an organism indefinitely with (b) the need for a central nervous system that maintains memory and state over time seems a challenging project, to say the least, however. At present it would be a major undertaking to alter one gene in the human genome while having any confidence that the outcomes are fully understood, let alone producing an entirely new functionally immortal higher species.

Thus for now it seems that the best approach to aging is based on repair. Don't try to alter the biochemistry that we have; accept its flaws, and attempt to repair the well-known forms of damage that accumulate with age as a result of those flaws. Comparatively little effort has so far been put towards building therapies capable of damage repair, while the specific desired forms of repair are quite well understood, that pursuing repair seems a much better use of time than building incremental first steps towards a distant future of an engineered, ageless genome.

Ageing as a software design flaw

Many theories of why we age have been proposed, including damaged-based and programmatic theories, with the former currently more widely accepted and studied. Most damage-based theories postulate that inefficient repair mechanisms result in singular or multiple, and often interacting, forms of damage accumulation. Although damage can be broadly defined as any change that affects function, here I refer more specifically to molecular damage hypothesized to drive ageing, such as by-products of metabolism, unwanted chemical modifications, and other types of molecular damage affecting crucial cellular components like the genome, telomeres, mitochondria, and proteins. By contrast, programmatic theories argue that ageing results from predetermined mechanisms encoded in the genome, rather than stochastic damage accumulation.

The concept of information in biology has a long history, and biological systems can be seen as highly complex information systems. Likewise, the idea that ageing could be linked to information decay or loss has been proposed, in particular in the context of the information theory of ageing. According to this theory, loss of genetic or epigenetic information with age, driven by DNA damage, is the primary cause of ageing. One hypothesis is that errors accrue in the DNA, corrupting the information in the genome and ultimately disrupting tissue homeostasis and causing ageing. More broadly, the idea that errors or damage to one or more biological types of hardware, including the DNA, accumulate and drive the process of ageing has been prevalent for decades. By hardware I encompass all elements of biological systems, including organs, tissues and the basic unit of life, the cell, and its structures (mitochondria, telomeres, proteins, DNA, and so on), most of which have at some point been hypothesized to be important in ageing.

What if, however, the processes that cause ageing are not a product of inevitable molecular damage but rather intrinsic features of the software? In this context, I define software as the genetic program, the DNA code that orchestrates how a single cell becomes an adult human being capable of reproducing, ultimately our evolutionary purpose. Herein, I present and explore the hypothesis that perhaps ageing is not a result of inevitable wear and tear or accumulated molecular damage in the hardware but rather that ageing is caused by design flaws in the software itself. I discuss manipulations of ageing and how they support this hypothesis, acknowledge exceptions, and lastly, propose areas of future study.