Distinct Longevity Mechanisms Across and Within Species & Their Association With Aging

Distinct longevity mechanisms across and within species and their association with aging

News Release, World Mitochondria Society, Berlin - Germany – June 26, 2023

Lifespan varies within and across species, but the general principles of its control remain unclear.

In their new study, published in Cell,  Vadim N. Gladyshev from Harvard Medical school and his team, conducted multi-tissue RNA-seq analyses across 41 mammalian species, identifying longevity signatures and examining their relationship with transcriptomic biomarkers of aging and established lifespan-extending interventions.

An integrative analysis uncovered shared longevity mechanisms within and across species, including downregulated Igf1 and upregulated mitochondrial translation genes, and unique features, such as distinct regulation of the innate immune response and cellular respiration.

Signatures of long-lived species were positively correlated with age-related changes and enriched for evolutionarily ancient essential genes, involved in proteolysis and PI3K-Akt signaling. Conversely, lifespan-extending interventions counteracted aging patterns and affected younger, mutable genes enriched for energy metabolism. The identified biomarkers revealed longevity interventions, including KU0063794, which extended mouse lifespan and healthspan.

In summary their research highlighted that:

  • Distinct molecular mechanisms control lifespan within and across species
  • Aging effects are reversed by longevity interventions but not by species longevity
  • Regulation of Igf1 and mitochondrial translation are shared signatures of longevity
  • Longevity signatures enable the discovery of geroprotectors, such as KU0063794

Overall, this study uncovers universal and distinct strategies of lifespan regulation within and across species and provides tools for discovering longevity interventions.

Aricle DOI.

Image Credits: Tyshkovskiy, Alexander et al. Cell, Volume 186, Issue 13, 2929 - 2949.e20

Targeting Mitochondria 2023 this October will dedicate a full session to "Mitochondria & Longevity: Towards Expanding Life Span". Submit a related abstract.


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