Death rates reflect accumulating brain damage in arthropods

Abstract

We present the results of the first quantitative, whole-lifespan study of the relationship between age-specific neurolipofuscin concentration and natural mortality rate in any organism. In a convenient laboratory animal, the African migratory locust, Locusta migratoria, we find an unusual delayed-onset neurolipofuscin accumulation pattern that is highly correlated with exponentially accelerating age-specific GompertzMakeham death rates in both males (rZ0.93, pZ0.0064) and females (rZ0.97, pZ0.0052). We then test the conservation of this association by aggregating the locust results with available population-specific data for a range of other terrestrial, freshwater, marine, tropical and temperate arthropods whose longevities span three orders of magnitude. This synthesis shows that the strong association between neurolipofuscin deposition and natural mortality is a phylogenetically and environmentally widespread phenomenon (rZ0.96, p!0.0001). These results highlight neurolipofuscin as a unique and outstanding integral biomarker of ageing. They also offer compelling evidence for the proposal that, in vital organs like the brain, either the accumulation of toxic garbage in the form of lipofuscin itself, or the particular molecular reactions underlying lipofuscinogenesis, including free-radical damage, are the primary events in senescence.

Aging and its modulation in a long-lived worker caste of the honey bee

“…That old winter bees with negligible behavioral senescence (Fig.1) still showed increased lipofuscin levels might indicate that behavioral senescence is preceded by cellular senescence. However, comparable studies also measured moderate lipofuscin levels throughout early adult life, followed by a marked increase towards the end of life, which is linked to functional decline and increased mortality (Double et al, 2008;Fonseca et al, 2005a). Similarly, long lifespan and lack of detectable behavioral decline in winter bees (Figs1, 2) suggest that intermediate lipofuscin levels in old winter bees are not associated with harmful cellular deterioration.…”

“…This implies that after caste transition lipofuscin accumulation rates are accelerated in the pars intercerebralis, a neurosecretory center. Although during normal aging, significant accumulation in the brain's pars intercerebralis is also documented for another insect, the African migratory locust (Locusta migratoria) (Fonseca et al, 2005a). Accumulation rates in this area were shown to reflect death rates, and thus increased frailty among individuals.…”

“…By comparing groups with accelerated and slowed behavioral senescence we asked how cellular senescence depends on worker phenotype and tissue identity. To this end, we quantified accumulation of lipofuscin, undegradable lipid-protein granules that are normally linked to chronological age and that are associated with functional decline as well as increased mortality (Double et al, 2008;Fonseca et al, 2005a;Hsieh and Hsu, 2011). Our results suggest that cellular senescence is not homogenous among tissues with different functions, and that lipofuscin accumulation is highly dynamic after the winter bee stage is disrupted.…”

“…In contrast to social phenotype transitions, it is well known that lipofuscin accumulates with chronological age (Fonseca et al, 2005a). This prompted us to evaluate the two parameters by comparing the groups with large differences in chronological age.…”

Neuronal Inputs and Outputs of Aging and Longevity

“…In contrast, most genes did not show a consistent age-dependent pattern across species, leading the authors to conclude that humans and rhesus macaques have greatly diverged from mice as demonstrated by a dramatic increase in age-dependent repression of human and macaque neuronal genes (Loerch et al, 2008). While these results indicate that the neuronal mechanisms of aging and longevity might not be highly conserved among different taxa, a study by Fonseca et al (2005) provides a remarkable counter-example. Across a range of terrestrial, freshwater, marine, tropical, and temperate arthropods, whose lifespans vary by three orders of magnitude, the neuronal deposition of lipofuscin, a lipid-protein aggregate, is highly correlated with lifespan.…”