In this insight, Dr. Alan Cohen of the Université de Sherbrooke shares with us the inspiration for, challenges, and messages behind his review article “Are trade-offs really the key drivers of aging and lifespan?”.

About the paper

What’s your paper about?

This review article challenges the long-held and widespread notion that trade-offs, particularly between survival and reproduction, are a sufficient explanation for why and how aging and lifespan evolve. It relies on our increasing mechanistic understanding of aging, as well as on both theoretical and empirical findings that suggest trade-offs are not always as strong as traditionally expected. Many mechanisms may serve more as constraints on lifespan than as modulable factors to be adjusted via trade-offs.

How did you come up with the idea for it?

At the Evolutionary Demography Conference in Lyon (Jan 2018), I was surprised to see 4-5 different talks that in one way or another called into question the strength or universality of trade-offs. I had recently published a more specific theoretical paper on the same subject (Cohen, A.A., Isaksson, C., Salguero-Gómez, R. (2017). Co-existence of multiple trade-off currencies has major impacts on evolutionary outcomes. PLOS ONE, 2(12):e0189124), and so I talked with the various presenters and proposed that we collaborate on a review, feeling the time was ripe. When I was contacted to contribute to this special issue (incidentally by the same to researchers that organized the conference in Lyon, Jean-Michel Gaillard and Jean-François Lemaître!), I suggested this topic.

What are the key messages of your article?

Trade-offs alone cannot fully explain taxonomic variation in aging and lifespan. We propose a framework in which both trade-offs and constraints operate to adjust lifespan and aging mechanisms across species, but with the relative importance changing across clades as a function of physiology and environment. In some cases, trade-offs may be crucial; in others, they may play little role.

How is your paper new or different from other work in this area?

I think few researchers would question the general statement that both adaptation and constraints shape evolution, and thus that the impact of trade-offs may be modulated by constraints. Nonetheless, the evolutionary impact of constraints on aging has been largely ignored. This is true even for the Mutation Accumulation Theory, which, though it does not rely on trade-offs, does rely on selection: it proposes that selection against deleterious mutations declines with the age of expression of the mutations. Constraint-based explanations for aging propose that the specific physiology of each species or clade imposes an upper limit on lifespan that is not subject to selection except insofar as the constraint itself can be eliminated on longer timescales. Conversely, the absence of important constraints might also serve to weaken the trade-offs and create situations in which some species largely escape aging.

About the research

Why is it important?

My perception generally is that many evolutionary biologists and ecologists tend to acknowledge constraints, and then set them aside and focus on adaptation. I hope that this paper will serve as a larger example of how the presence of constraints can change our understanding of how adaptation happens, and force us to more deeply consider the interplay between the two.

Did you have any problems writing your article?

Obviously, as a review article there weren’t really data here, but we certainly had challenges with the article. The biggest was communication: my brief summary above makes it seem simple, but we needed to define terms and limit the scope: did we focus on both interspecific and intraspecific evidence of trade-offs, or just one? Did we focus on survival vs. reproduction trade-offs, or all trade-offs? The literature is vast, and my main research area is on understanding the aging process, so I often felt out of my depth. First with my co-authors, and then with reviewers and editors, we had many challenges in understanding each other. Overcoming those challenges led to a final paper I think we are all very proud of. I learned a great deal from the process!

As a specific example, just before submitting the final version of the manuscript, it became clear that my co-authors and I did not even really agree on what a trade-off was, and this was creating confusion! I had always conceived of trade-offs on a mechanistic level – for example, ATP allocated to generating offspring versus allocated to repairing DNA damage. Some of my co-authors conceived of trade-offs as patterns of negative correlations among fitness components, whereas I conceived of them as mechanisms subject to selection that create those patterns. It was the most junior member of the team, Salomé Bourg, who wisely suggested we should add a definition. That solved the problem quite nicely!

What does your work contribute to the field?

The article is at the intersection of two fields: aging biology and evolutionary ecology. For evolutionary ecology, it suggests that we may be overestimating the importance of trade-offs in contexts well beyond the evolution of aging. The principles we identify should apply to nearly all trade-offs. The impact on aging biology is two-fold. First, our article contributes to an increasing literature questioning the classical evolutionary theories of aging. While those theories explain much, they do not explain everything, and a larger framework is needed. Second, it proposes that we can start to classify known aging mechanisms by how they would respond (or not) to selection; in other words, whether they are the basis of a trade-off or a constraint, or some combination.

What are the big questions still to answer?

• Many aging mechanisms appear to be universal, or nearly-universal, biological processes. How then can many species be essentially immortal? In our terms, why are they able to escape from constraints?
• Can we start to map aging mechanisms across the tree of life to arrive at a coherent understanding of how it evolves both mechanistically and demographically?
• Some genetic control over the aging process is highly conserved from yeast to nematodes to mammals. How then can intermediate clades escape aging altogether? What do these genes do in non-aging animals?

About The Author

How did you get involved in ecology?

I started my Ph.D knowing that I wanted (a) to spend time outdoors with critters, and (b) understand aging, which seemed – and still seems – to be one of the great remaining mysteries. Ecology was the obvious choice.

What are you currently working on?

I am at a Faculty of Medicine, and thus have little time left for ecology, and no time whatsoever for field work. L. Most of my work uses statistics and complex systems theory to try to understand and measure underlying physiological/biological processes that are not evident by looking at biomarkers one at a time. I mostly apply this to quantify loss of homeostasis as an emergent aging process, but I have other projects looking at aging/death as critical transitions in complex systems, or using ecosystem models to understand the immune system as a whole.

What’s your current position?

Associate Professor, here now for 9 years.

What project/article are you most proud of?

Probably my first article, Cohen, A.A.(2004). “Female Post-Reproductive Lifespan: A General Mammalian Trait,” Biological Reviews, 79: 733-750. I showed that menopause-like phenomena are widespread among mammals, and proposed that physiological constraints create a disconnect between rates of reproductive and somatic senescence. Humans females in this context are unique for the duration, but not the presence, of a post-reproductive period.

What do you do in your spare time?

Aikido and improvisational dance.

One piece of advice for someone in your field…

Faculty jobs are scarce in eco/evo. Consider moving toward the biomedical world, where an eco/evo perspective is sorely needed (good stats, systemic thinking), and where there may be unique opportunities to apply your skills in creative interdisciplinary ways. However, beware of two pitfalls: (1) Everyone loves interdisciplinary in theory, but in practice there are tons of barriers. (2) The problems in the science system (cutthroat competition, metric-based judging of research and researchers, etc.) are worse in the biomedical world than in eco/evo.

You can read the paper in full here or the free plain language summary here. This paper This paper is part of a Special Feature: An Integrative View of Senescence in Nature (to be published Autumn 2019).