In vivospectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction inCaenorhabditis elegans

Abstract

SummaryAutofluorescent lipofuscin and advanced glycation end-products (age pigments) accumulate with age across phyla, yet little is understood about their formation under physiological conditions and their specific contributions to the aging process. We used in vivo spectrofluorimetry to quantitate autofluorescence in wild-type Caenorhabditis elegans and longevity mutants disrupted for distinct aspects of the aging process. In wild-type animals, age pigments increase into adulthood, accumulating slowly during the reproductive phase and more rapidly during the post-reproductive period. As in humans, insulin signaling influences age pigment accumulation -mutations that lower efficacy of insulin signaling and extend lifespan [ daf-2 ( e1370 ) insulin receptor and age-1 ( hx546 ) PI3-kinase] dramatically lower age pigment accumulation; conversely, elimination of the insulin-inhibited DAF-16/ FOXO transcription factor causes a huge increase in age pigment accumulation, supporting that the short-lived daf-16 null mutant is truly progeric. By contrast, mutations that increase mitochondrial reactive oxygen species production do not affect age pigment accumulation, challenging assumptions about the role of oxidative stress in generating these species in vivo . Dietary restriction reduces age pigment levels significantly and is associated with a unique spectral shift that might serve as a rapidly scored reporter of the dietary restricted state. Unexpectedly, genetically identical siblings that age poorly (as judged by decrepit locomotory capacity) have dramatically higher levels of age pigments than their same-aged siblings that appear to have aged more gracefully and move youthfully. Thus, high age pigment levels indicate a physiologically aged state rather than simply marking chronological time, and age pigments are valid reporters of nematode healthspan.

The role of lysosomes in iron metabolism and recycling

“…Finally, when wild-type siblings that aged differently -as evaluated by changes in their motility -were compared, it was found that the still mobile and youthful ones at day 11 of their life spans contained only 25% of the lipofuscin that was found in severely motility-impaired siblings of the same age. This implies that lipofuscin accumulation reflects biological rather than chronological age (Gerstbrein et al, 2005). The positive correlations between lipofuscin accumulation and hampered cellular function are in harmony with observations that chronic feeding of rats with green tea between the age of 12 and 19 months delays hippocampal accumulation of lipofuscin and improves learning and memory.…”

Systems biology of aging in four species

“…Previously, whole-genome transcriptional profiles of worm populations of varying ages were generated using DNA microarrays [8,9] A concept of interest is to use biomarkers of aging to predict the lifespan of individuals within a population with an identical age and sharing the same environment. Levels of lipofuscin, a pigment thought to correlate with physiological age, were found to predict the remaining lifespan of worms [14]. Golden et al performed DNA microarray analyses on individual worms, with the aim of discovering genes that vary stochastically amongst individuals within an age-matched population [15,16].…”

3-Ketoacyl thiolase delays aging ofCaenorhabditis elegansand is required for lifespan extension mediated bysir-2.1

“…These biomarkers include behavioral decline and tissue aging (8)(9)(10)(11). Aging of C. elegans is characterized by a progressive decline in locomotion, both in speed and coordination (9,10,12), and decreased defecation and pharyngeal pumping rate (8,9,13). Old nematodes, like old humans, show progressive tissue and organ deterioration: muscles, gonad, intestine, and connective tissues degenerate in aged worms (9)(10)(11).…”