Extraordinary plasticity in aging in Strongyloides ratti implies a gene‐regulatory mechanism of lifespan evolution

Abstract

SummaryAging evolves as the result of weakened selection against late-acting deleterious alleles due, for example, to extrinsic mortality. Comparative studies of aging support this evolutionary theory, but details of the genetic mechanisms by which lifespan evolves remain unclear. We have studied aging in an unusual nematode, Strongyloides ratti , to gain insight into the nature of these mechanisms, in this first detailed examination of aging in a parasitic nematode. S. ratti has distinct parasitic and free-living adults, living in the rat small intestine and the soil, respectively. We have observed reproductive and demographic aging in parasitic adults, with a maximum lifespan of 403 days. By contrast the maximum lifespan of free-living adults is only 5 days. Thus, the two adults of S. ratti have evolved strikingly different rates of aging. Parasitic nematode species are frequently longer-lived than free-living species, presumably reflecting different extrinsic mortality rates in their respective niches. Parasitic and free-living female S. ratti are morphologically different, yet genetically identical. Thus, the 80-fold difference in their lifespans, the greatest plasticity in aging yet reported, must largely reflect evolved differences in gene expression. This suggests that interspecific differences in lifespan may evolve via similar mechanisms.

Genome-Environment Interactions That Modulate Aging: Powerful Targets for Drug Discovery

“…S. ratti is a parasite, the free-living form is very short-lived (ϳ5 days), yet once inside a host, female worms can live for more than a year (Gardner et al, 2006). These remarkable (Ͼ50-fold) differences in lifespan from the same genome are, as far as we are aware, the largest lifespan difference caused by the environ-AGING GENES AS TARGETS FOR DRUG DISCOVERY ment.…”

Transgenesis inStrongyloidesand related parasitic nematodes: historical perspectives, current functional genomic applications and progress towards gene disruption and editing

“…Strongyloides ratti is arguably the best studied of the animal parasitic Rhabditida in terms of its evolutionary (Gemmill et al 2000; Dorris et al 2002; Fenton et al 2004), developmental (Viney, 1996; Harvey et al 2000; Crook and Viney, 2005; Gardner et al 2006) and reproductive biology (Viney et al 1993; Viney, 1994; Harvey and Viney, 2001) and in terms of ecological aspects of its relationship with its host (Harvey et al 1999; Wilkes et al 2004, 2007; Paterson et al 2008; O'Meara et al 2010). Moreover, studies of S. ratti have been at the forefront of genome- and transcriptome-scale investigations of the evolution of parasitism in parasitic nematodes (Thompson et al 2005, 2006, 2008, 2009; Spinner et al 2012).…”

Hormesis does not make sense except in the light of TOR-driven aging

“…Even humans, long-living organisms, do not die from a decline due to such an accumulation. (And of course worm that lives just 5 days [67] cannot possibly accumulate deadly levels of molecular damage). Instead any human being has died from age-related diseases, which are caused by active cellular processes initiated by hyper-activation of signaling pathways including mTOR [36, 68].…”