Some Thoughts About Aging
Nothing groundbreaking
Aging is Not a Singular Thing
It's popular to talk about aging clocks measuring some latent variable that is "aging," but I think this view is flawed. Aging is not a unified mechanism, rather, there are many processes going on in parallel, each deleterious in its own way. Some are interrelated and correlated, but there is also independence among them. It’s entirely possible that one specific form of damage reaches a lethal threshold while others lag far behind, perhaps due to a mutation making someone particularly vulnerable to that type of damage. Thus, there's no reason to believe in a singular aging variable. One might find factors correlating strongly with morbidity and mortality, or even measure specific molecular damage types that cause morbidity. Aggregating these damage markers could give a good proxy for mortality. However, there's no way to accurately predict death because death itself is a stochastic event occurring at the systems level. Probably many different ways exist to aggregate various sets of factors to obtain equally good predictions, and there’s no single “correct” one. While we might still call these aggregates "aging clocks," the debate about whether they measure "aging" per se misses the point. Aging, rather, should be understood as probabilistic predictors of system collapse - death - not as a single unified biological entity. I summary, aging isn't a hidden essence. It's a cluster of loosely related deteriorative processes whose combined influence probabilistically leads to death.
The Hallmarks Paradigm is Misguided
Since the 2013 publication of the "Hallmarks of Aging," there’s been an obsession with defining aging through a finite list of hallmark processes. People continuously try adding more hallmarks or point out supposedly underappreciated ones. Yet in reality, aging affects every aspect of biology at every organizational level - genome, epigenome, transcriptome, metabolome, matrisome, indeed any "-ome" one might imagine. Anywhere you look, you find changes that are antagonistic to aging, protagonistic, or neutral. There's no simple set of root causes from which everything else flows. Aging is better understood as a complex, intertwined network filled with feedback loops rather than a neatly organized set of hallmark categories. An exhaustive list will absurdly cover all of biology, which would make it pointless, so this quest can be put to rest.
Aging is Not Programmed in the Hard Sense
By "programmed," I specifically mean there's a defined sequence of energetically demanding events that, if interrupted, would terminate aging. I think there isn’t a genetic sequence explicitly designed to age an organism (i.e., isn't like puberty, driven actively by genetic switches). I think the rate of aging and an organism’s lifespan are indeed determined by genetic and epigenetic programs, but these programs become hardwired early in development. Development shapes structures, maintenance mechanisms, and repair efficiency. Different species, even closely related, have widely varying lifespans determined by these early-life genetic and epigenetic programs. A grown organism thus has a limited lifespan already established. Still, there is some leeway, which interventions can exploit. Fundamentally, aging is about damage accumulation and structural decline due to entropy. This is obvious through observation: a young versus old person mirrors a young versus old car. The efficiency of repair and homeostasis mechanisms determines the rate at which this structural deterioration occurs. Thus, aging is not programmed in the sense of actively driving damage; rather, it’s a passive phenomenon defined by how much attention an organism gives to damage control and how effectively it can eliminate or mitigate such damage to retain structural integrity. Interventions may boost certain mechanisms, perhaps at the expense of others. Therefore, aging is pre-programmed genetically and epigenetically, but this programming occurs early in life. Beyond this developmental window, lifespan is probably fixed unless entirely new repair mechanisms are introduced.
Uncertain Why Aging Evolved in the First Place
It remains uncertain precisely why aging evolved at all. Logically, one might argue that an individual who does not age would hold a significant evolutionary advantage, eventually dominating the population. Yet, empirically, aging is the norm across nearly all life forms. There's no fundamental biological limitation on how long you could potentially live, so there must be another reason why aging is so widespread. Selection shadow alone - the idea that selection pressure diminishes with increasing age - doesn't entirely explain this. Even if the evolutionary returns diminish as organisms age, they're still present, offering a fitness advantage that would presumably accumulate over time. Some speculate about tradeoffs, suggesting either traits beneficial during youth become detrimental with age (antagonistic pleiotropy) or that there's a fertility-maintenance tradeoff due to limited energetic resources (disposable soma). But, the first idea seems like a stretch to me - why would benefits early in life necessarily be harmful later on as a general rule? The second idea also seems unconvincing: how much extra energy would it really require not to age? Is the energetic cost truly so substantial that it outweighs the advantage of extended lifespan? I doubt it. Others propose population-level selection as an explanation, suggesting that immortal populations might collapse due to resource limitations or slowed adaptation, but if this were a strong reason, you'd expect to have observed at least some populations like that existing somewhere, and we don't. Maybe a more plausible explanation is that it's genetically and biologically complex to substantially delay aging, and therefore it happens rarely and only under strong, consistent selection pressures. Perhaps a lineage would need multiple mutations all aligning correctly, and the evolutionary conditions for such mutations to accumulate might be quite rare. This complexity argument might be the best explanation I can com up with, but even that doesn't feel fully satisfying to me.
We are Far from Radical Life Extension, and Focusing on Aging Research Won't Help Much
Some voices advocate for investing more effort into studying aging and reversing it. However, I think the problem is fundamentally one of technological readiness, not insufficient research focus. Consider that a century ago, no matter how much the world had invested into aging research, meaningful progress would have been impossible - not from lack of effort, but due to the absence of basic tools for measurement and biological manipulation. Today, we face similar limitations. In contrast, the Manhattan Project and Apollo Program succeeded not because of a sudden burst of interest, but because the necessary technological foundations were already in place - or within reach. In aging, we simply aren’t there yet. As aging is not programmed in the hard sense, current interventions, especially small molecules, are inherently limited. Such interventions mainly attempt to activate or enhance pre-existing repair pathways. But these endogenous repair pathways have fundamental limitations: they cannot address every form of damage, and those they can are often repaired inefficiently or incompletely. Therefore, achieving true breakthroughs requires entirely new technological tools to design, engineer, and introduce novel repair infrastructures into our cells and between them. These engineering breakthroughs, largely unrelated to traditional aging research, are currently beyond our grasp. Without them, merely focusing more resources on aging research will likely yield little meaningful progress toward radical life extension. We need new technologies - game changers like AGI - to facilitate and accelerate the development of these engineering tools. And we should seriously consider alternative approaches such as cybernetic consciousness preservation, which also depend on major breakthroughs but offer a viable hedge in the meantime.
