Xenotopic synthetic biology: Prospective tools for delaying aging and age-related diseases

Andrey A Parkhitko1, Valentin Cracan2,3

  • 1Aging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.

Science Advances
|March 28, 2025
PubMed

Insights

Leveraging enzymes from other species offers a novel strategy to combat aging. These non-mammalian enzymes can reverse age-related metabolic changes, potentially delaying aging and age-related diseases.

Area of Science:

  • Biochemistry
  • Gerontology
  • Molecular Biology

Background:

  • Metabolic dysregulation is a key driver of aging.
  • Genetic and pharmacological interventions show limitations in preventing age-dependent decline.
  • Aging is a complex process influenced by multiple metabolic factors.

Purpose of the Study:

  • To review enzymes from lower organisms that modulate age-associated metabolic parameters.
  • To explore the potential of non-mammalian enzymes in reversing metabolic changes linked to aging.
  • To propose a novel strategy for delaying aging and age-related diseases.

Main Methods:

  • Literature review of enzymes affecting amino acid levels, redox potentials, glutathione, mitochondrial membrane potential, and reactive oxygen species.
  • Analysis of enzymes including METase, ASNase, ADI, NDI1, AOX, LbNOX, TPNOX, EcSTH, RquA, LOXCAT, Grubraw, ScURA, StGshF, mtON, mito-dR, DAAO, and KillerRed-SOD1.
  • Discussion of how these enzymes impact metabolic pathways relevant to aging.

Main Results:

  • Identified various non-mammalian enzymes that modulate key metabolic parameters associated with aging.
  • Demonstrated the potential of these enzymes to influence amino acid homeostasis, redox balance, and oxidative stress.
  • Highlighted enzymes affecting mitochondrial function and glutathione levels.

Conclusions:

  • Non-mammalian enzymes represent an underutilized resource for anti-aging strategies.
  • Targeting age-associated metabolic dysregulation with exogenous enzymes offers a promising therapeutic avenue.
  • This approach could lead to interventions for delaying aging and mitigating age-related diseases.