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Updated: Aug 17, 2025

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A conserved MTMR lipid phosphatase increasingly suppresses autophagy in brain neurons during aging

Tibor Kovács1, Janka Szinyákovics1, Viktor Billes1,2

  • 1Department of Genetics, ELTE Eötvös Loránd University, Pázmány Péter Stny. 1/C, Budapest, 1117, Hungary.

Scientific Reports
|December 17, 2022
PubMed

Insights

Cellular damage accumulation drives aging. Researchers found that the egg-derived tyrosine phosphatase (EDTP) enzyme increasingly suppresses autophagy, a cellular self-cleaning process, in fruit fly brain neurons with age, promoting brain aging.

Area of Science:

  • Cellular biology
  • Neuroscience
  • Aging research

Background:

  • Aging is characterized by accumulating cellular damage.
  • Autophagy, a cellular self-eating process, clears cellular damage but declines with age.
  • The precise reasons for age-related autophagy decline remain unclear.

Purpose of the Study:

  • To investigate the mechanisms behind age-associated defects in autophagic degradation.
  • To identify factors contributing to the decline of autophagy in aging neurons.
  • To explore the role of egg-derived tyrosine phosphatase (EDTP) in brain aging.

Main Methods:

  • Studied age-associated defects in both early and late stages of autophagic degradation.
  • Investigated the accumulation of EDTP, an autophagy repressor, in adult fruit fly brain neurons.
  • Examined the correlation between EDTP activity, DNA N6-adenine methylation, and aging.
  • Assessed the age-related accumulation of MTMR14, the human homolog of EDTP, in brain neurons.

Main Results:

  • Age-associated defects in autophagy occur at multiple stages.
  • EDTP accumulates in fruit fly brain neurons throughout adulthood, repressing autophagy.
  • Increased EDTP activity correlates with rising DNA N6-adenine methylation at the EDTP locus.
  • Human MTMR14 also shows age-related accumulation in brain neurons.

Conclusions:

  • EDTP and its human counterpart MTMR14 act as endogenous pro-aging factors by suppressing neuronal autophagy.
  • These phosphatases may set the pace of brain aging, independent of environmental factors.
  • Autophagy regulation is influenced by DNA N6-methyladenine levels in insects.

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