Abstract
Organismal lifespan has been the primary readout in aging research. However, how longevity genes control tissue-specific aging remains an open question. To examine the crosstalk between longevity programs and specific tissues during aging, biomarkers of organ-specific aging are urgently needed. Since the earliest signs of aging occur in the skin, we sought to examine skin aging in a genetically tractable model. Here we introduce a Drosophila model of skin aging. The epidermis undergoes a dramatic morphological deterioration with age that includes membrane and nuclear loss. These changes were decelerated in a long-lived mutant and accelerated in a short-lived mutant. An increase in autophagy markers correlated with epidermal aging. Finally, the epidermis of Atg7 mutants retained younger characteristics, suggesting that autophagy is a critical driver of epidermal aging. This is surprising given that autophagy is generally viewed as protective during aging. Since Atg7 mutants are short-lived, the deceleration of epidermal aging in this mutant suggests that in the epidermis healthspan can be uncoupled from longevity. Because the aging readout we introduce here has an early onset and is easily visualized, genetic dissection using our model should identify other novel mechanisms by which lifespan genes feed into tissue-specific aging.
Highlights
Life expectancy is currently increasing in both developed and developing countries
We first tested if Drosophila adult epidermal morphology changes with age
Epidermal knockdown of Atg7 resulted in decelerated epidermal aging similar to the mutant, suggesting a tissue-autonomous role for autophagy (Fig. 6D). These results suggest that changes in epidermal morphology with age are driven by autophagy
Summary
Life expectancy is currently increasing in both developed and developing countries. In turn, agerelated health problems represent a growing socioeconomic challenge for society. Genetic model systems like the fruit fly Drosophila have allowed the identification of evolutionarily conserved genes that control longevity [1, 2] , such as insulin-like peptides [3] and TOR signaling [4, 5] These studies have generally used lifespan of population cohorts as a primary readout. C. elegans muscles show early signs of deterioration, while the nervous system remains remarkably intact [7] This likely reflects the fact that individual tissues make different contributions to lifespan, suggesting that their healthspans may be regulated differently. An open question about the relationship between lifespan and healthspan is how longevity genes differentially control individual tissuespecific aging programs To examine this issue, simple and early visual tissue biomarkers of “aging in progress” are urgently needed. Most of these organs and behaviors either have a complex morphology and www.impactaging.com
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