A virus-acquired host cytokine controls systemic aging by antagonizing apoptosis

PLoS Biol. 2018 Jul 23;16(7):e2005796. doi: 10.1371/journal.pbio.2005796. eCollection 2018 Jul.

Abstract

Aging is characterized by degeneration of unique tissues. However, dissecting the interconnectedness of tissue aging remains a challenge. Here, we employ a muscle-specific DNA damage model in Drosophila to reveal secreted factors that influence systemic aging in distal tissues. Utilizing this model, we uncovered a cytokine-Diedel-that, when secreted from muscle or adipose, can attenuate age-related intestinal tissue degeneration by promoting proliferative homeostasis of stem cells. Diedel is both necessary and sufficient to limit tissue degeneration and regulate lifespan. Secreted homologs of Diedel are also found in viruses, having been acquired from host genomes. Focusing on potential mechanistic overlap between cellular aging and viral-host cell interactions, we found that Diedel is an inhibitor of apoptosis and can act as a systemic rheostat to modulate cell death during aging. These results highlight a key role for secreted antagonists of apoptosis in the systemic coordination of tissue aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Apoptosis*
  • Cytokines / metabolism*
  • DNA Damage
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / physiology*
  • Hormesis
  • Intestines
  • Longevity
  • Mice
  • Muscles / metabolism
  • Viruses / metabolism*

Substances

  • Cytokines
  • Diedel protein, Drosophila
  • Drosophila Proteins

Grant support

AFAR Research Grant https://www.afar.org/research/ (grant number). Received by JK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.