Fight Aging!

Why does aging exist? Why, when we look about the world, can we only find two defensible examples of an immortal species, the hydra and the jellyfish Turritopsis dohrnii? There are a few other species that might be immortal, but the evidence is fairly shaky in near all cases, meaning that it is more of a challenge than is usually the case to show aging, or the data is sparse. These species are probably only negligibly senescent, meaning that they tend to decline rapidly at the end of life and otherwise show few signs of aging up until that point. Lobsters fall into this category, for example. Given that there is exactly one species with good evidence of its immortality - no-one has yet run an equivalent to the rigorous testing of hydra mortality rates in Turritopsis dohrnii - and countless species that clearly age, what are the odds that any given species with poor data is actually immortal? Not so good, I think.

The authors of the paper noted below have an interesting view on why aging is an inevitable outcome of evolutionary processes. To their eyes the declines of aging are an emergent property of competition between classes of cell in multicellular organisms. You might contrast this with the view that aging is a race to the bottom that occurs because environments change, often radically in comparatively short periods of time, and species in which individuals age have a greater ability to adapt to that change than species in which individuals are immortal. Thus aging species out-compete the immortal species in every evolutionary niche over long periods of time. That model has the advantage of predicting that we might see a few immortal species at any given moment, but we should not expect them to last. So while the paper below is thought-provoking, the primary problem I see here is that there is no acknowledgement of the existence of hydra - something of a challenge to a model that presents aging as absolutely inevitable.

In fact, the authors come on very strong with this view of aging as inevitable and beyond our power to defeat in the publicity materials. I have to think that they are quoted out of context and the quotes then assembled by someone who doesn't understand the research, which entirely relates to the evolution of aging, not our ability to intervene in the aging process. How it is we find ourselves stuck in these corroding bodies is a somewhat separate topic from what we choose to do about it - meaning the identification of the best strategies for periodic repair of our failing biochemistry. So I'd say skip the publicity materials, which I think are trying, poorly, to express the idea that there is no way to prevent breakage from occurring in cellular biochemistry, and go straight to the paper. It isn't open access, but the usual way past those barriers works just fine.

It's mathematically impossible to beat aging, scientists say

"Aging is mathematically inevitable - like, seriously inevitable. There's logically, theoretically, mathematically no way out. As you age, most of your cells are ratcheting down and losing function, and they stop growing, as well. But some of your cells are growing like crazy. What we show is that this forms a double bind - a catch-22. If you get rid of those poorly functioning, sluggish cells, then that allows cancer cells to proliferate, and if you get rid of, or slow down, those cancer cells, then that allows sluggish cells to accumulate. So you're stuck between allowing these sluggish cells to accumulate or allowing cancer cells to proliferate, and if you do one you can't do the other. You can't do them both at the same time."

Although human mortality is an undisputed fact of life, the researchers' work presents a mathematical equation that expresses why aging is an "incontrovertible truth and an intrinsic property of being multicellular. People have looked at why aging happens, from the perspective of 'why hasn't natural selection stopped aging yet?' That's the question they ask, and implicitly in that is the idea that such a thing as non-aging is possible, so why haven't we evolved it? We're saying it's not just a question of evolution not doing it; it can't be done by natural selection or by anything else."

"You might be able to slow down aging but you can't stop it. We have a mathematical demonstration of why it's impossible to fix both problems. You can fix one problem but you're stuck with the other one. Things will get worse over time, in one of these two ways or both: Either all of your cells will continue to get more sluggish, or you'll get cancer. And the basic reason is that things break. It doesn't matter how much you try and stop them from breaking, you can't."

Intercellular competition and the inevitability of multicellular aging

Whereas mutation accumulation and antagonistic pleiotropy theory address the role of organismal selection in aging, we ask here whether aging is a fundamental and intrinsic feature of multicellular life. For an organism to avoid aging, it must overcome or mitigate the consequences of heritable changes in somatic cells, the vast majority of which are deleterious, and hence best thought of as "damage." Heritable cellular degradation is a product not just of somatic mutations but also of other changes, such as epigenetic drift and the accumulation of misfolded proteins. In unicellular organisms, competition between cells can weed out deleterious heritable changes, allowing a population to exist indefinitely despite individual degradation. Just as competition between individuals can eliminate deleterious alleles from a unicellular population, competition between cells within a multicellular organism can weed out malfunctioning, slower growing cells within an organism. Therefore, intercellular competition seems to hold the potential for immortality; by continually eliminating damaged cells, a multicellular organism might persist in perpetuity if only selection to do so were somehow strong enough.

Aging in multicellular organisms occurs at both the cellular and intercellular levels. Multicellular organisms, by definition, require a high degree of intercellular cooperation to maintain homeostasis. Often, cellular traits required for producing a viable multicellular phenotype come at a steep cost to individual cells. Conversely, many mutant cells that do not invest in holistic organismal fitness have a selective advantage over cells that do. If intercellular competition occurs, such "cheater" or "defector" cells may proliferate and displace "cooperating" cells, with detrimental consequences for the multicellular organism. Cancer, a leading cause of death in humans at rates that increase with age, is one obvious manifestation of cheater proliferation.

Thus, intercellular competition proves to be a double-edged sword; competition can remove damaged cells, but competition can also allow cheating cells to prosper. Here, we derive a general model of the effect of somatic evolution on aging and examine the behavior of a related model of discrete genotypes in simple numerical cases. Aging is characterized by the dual, but seemingly contradictory, features of loss of cellular vigor and uncontrolled cell growth, and we model the evolution of two corresponding cellular traits. First, we use the term "vigor" to reflect general cellular function or metabolic activity. Second, we use the term "cooperation" to represent investment in traits that are costly to the cell but beneficial for the organism as a whole; one manifestation of loss of cooperation is an increased propensity toward cancer. We show that intercellular competition produces a double bind resulting in inevitably declining organismal vitality with age in multicellular organisms.

Given most organisms' capacity to grow and regenerate, aging does not seem, at first glance, inevitable. Consequently, many have argued that aging is an accident of imperfect selection, where selection fails to purge deleterious, age-related mutations from an otherwise potentially immortal genotype. We have shown that even if selection against aging could be made more powerful, aging would remain an inescapable facet of multicellular life. As our model addresses the role of somatic evolution in aging, it should be seen as complementary, rather than contradictory, to models of aging via evolution by natural selection of multicellular individuals. Our model points to intercellular competition as a key factor in navigating the double bind of cellular degradation and cancer. It suggests that research programs focusing on quantifying the degree of intercellular competition and making comparisons across taxa, among individuals in the same population, among tissues of the same individual, and across developmental time, may be key to understanding the evolution and progress of aging.