Chapman, Hannah et al. (2021) International Worm Meeting "Does programmed organismal death promote fitness at the C. elegans colony level?"

Gems, David, Chapman, Hannah, Galimov, Evgeniy R.

[International Worm Meeting, 2021]

Is aging a form of programmed death which, like programmed cell death, promotes fitness? According to evolutionary theory, the answer is no, at least for species that reproduce as outbred dispersed populations. However, it is theoretically possible for adaptive death to evolve in species with clonal, colonial modes of existence, including bacteria, budding yeast and, potentially, C. elegans (1-3). Adaptive benefits of programmed organismal death in post-reproductive adults include increasing food availability for kin (consumer sacrifice) and consumption of dead adults by kin (biomass sacrifice)(1-3). Occurrence of adaptive death in C. elegans could partially explain the presence of so many genes where loss of function increases lifespan (1). We recently created an in silico model of a C. elegans colony on a virtual food patch to probe the likelihood that earlier adult death could increase fitness at the colony level. For the latter, dauer yield per colony was used as a metric. Behavior of the model supported the hypothesis that traits that reduce individual worm fitness can increase colony fitness (4). Increased colony fitness was sometimes observed not only when adult lifespan was shorter but also when brood size was reduced. Notably, reduction of brood size could increase the efficiency with which food was converted into dauer yield. Our findings supported the hypothesis that colony fitness is a function of population structure (4). To test this we have been altering C. elegans colony structure by varying founder animal number, and measuring colony fitness using a dauer yield assay. Results will be presented at the meeting. This work draws attention to the possibility that many characteristics of individual nematodes may promote fitness at the colony level rather than the individual nematode level. (1) J.N. Lohr, E.R. Galimov, D. Gems. Ageing Res. Rev. (2019) 50: 58. (2) E.R. Galimov, D. Gems, Biochem. (Moscow) (2019) 84: 1433. (3) E.R. Galimov, D. Gems, Phil. Trans. R. Soc. London (2021) 376: 20190730. (4) E.R. Galimov, D. Gems, Aging Cell (2020) 19 e13141.

Gems, David et al. (2021) International Worm Meeting "Three programmatic mechanisms of aging in C. elegans"

Galimov, Evgeniy, Kern, Carina, Gems, David

[International Worm Meeting, 2021]

One of the main objectives of research on aging in C. elegans is to develop an understanding of the fundamental principles that govern the process of senescence (aging) including the development of diseases of aging. Attaining this understanding has proven to be difficult, despite major advances in terms of knowledge of genes and pathways which affect lifespan. Work in the Gems lab has investigated two different ideas about aging in C. elegans. First, and initially, that it results mainly from the accumulation of stochastic molecular damage. Second, and more recently, that it results mainly from non-stochastic programmatic mechanisms driven by wild-type gene action. Tests of the damage theory yielded largely negative effects [1-6]. By contrast, tests of programmatic theories have both supported such theories [7-11] and led to elaborations of them [12-16]. Our recent work suggests a new picture of C. elegans aging as driven by three distinct forms of programmatic mechanism. First, programs optimized for fitness in early life that later run on in futile fashion, causing pathology. This is exemplified by uterine tumor formation which results from run-on of embryogenetic programs [10, 11], consistent with recent programmatic theories [17-19]. Second, costly programs that promote aging as part of a suicidal reproductive effort (semelparous reproductive death, c.f. Pacific salmon). For example, consumption of intestinal biomass to support production of yolk that is vented to support larval growth leads to gut atrophy (see presentation by C.C. Kern)[8, 16, 20]. Third, programmed adaptive death, that can evolve in organisms that exist in clonal, high-density populations and, particularly, where reproductive death occurs [12-14]. We suggest that the unusually high degree of plasticity in aging in C. elegans reflects suppression of genetically determined reproductive death and adaptive death. [1] Free Radic Biol Med (2003) 34, 277. [2] Free Radic Biol Med (2004) 37, 239. [3] Free Radic Biol Med (2011) 51, 1575. [4] Genes Dev (2008) 22, 3236. [5] Cell Cycle (2009) 8, 1681. [6] Mech Ageing Dev (2012) 133, 282. [7]. Oncotarget (2016) 7, 39082. [8] Curr Biol (2018) 28, 2544. [9] Antioxid Redox Signal (2013) 19, 321. [10] Aging (2018) 10, 1188. [11] NPJ Aging Mech Disease (2018) 4, 6. [12] Philos Trans R Soc B (2021) 376, 20190730. [13] Ageing Res Rev (2019) 50, 58. [14] Biochem (Moscow) (2019) 84, 1433. [15] Preprints (2020) 2020110019. [16] BioRxiv (2020) doi.org/10.1101/2020.1111.1115.380253. [17] Physiol (2005) 20, 252. [18] Cell Cycle (2006) 5, 2087. [19] Proc Biol Sci (2019) 286, 20191604. [20] J Gerontol A (2019) 74, 1180.

Ali, Irtiqa et al. (2021) International Worm Meeting "Investigating the basis of severe stress resistance in ageing"

Ackerley, Jacob, Benedetto, Alexandre, Ali, Irtiqa, Zarate-Potes, Alejandra, Martin, Jack

[International Worm Meeting, 2021]

Key words Severe stress resistance, ageing, CeMbio, IIS, oxidative, heat. Abstract Stress resistance and longevity are robustly correlated across heat stress paradigms but not oxidative stress paradigms. In particular, severe stress resistance in ageing C. elegans markedly differs between exposure to oxidative and heat stress that kill wild type worms within a couple of hours (Benedetto et al. Aging Cell 2019). Severe stress resistance may engage multiple mechanisms such as basal stress handling vs adaptive stress response pathways, different stress transduction pathways, the ability to execute the organismal death program (Galimov et al. 2019), or protection/sensitisation conferred by the gut microbiota. To disentangle these and evaluate their relative roles in ageing worms, we are screening C. elegans mutant in combination with strains from CeMBio collection for resistance to 7% tert-butyl hydroperoxide (t-BHP) and 42oC heat-shock as severe oxidative stress and thermal stress paradigms, respectively, before contrasting these results with aged animals. We are performing these screens on young adults at first, before moving into aged worms. So far, we have found that the capacity to execute the organismal death pathway does not significantly impact severe stress resistance in young adults fed an OP50 diet. However, young adults fed on 48 different bacterial isolates displayed varying levels of severe heat and oxidative stress resistance, some of which were insulin/IGF1-signalling (IIS) pathway-dependent. We are currently investigating the basis of these differences. This poster will provide an overview of the methods used, current results and planned future work.