2. Academic Validation
  3. Dietary supplementation of clinically utilized PI3K p110α inhibitor extends the lifespan of male and female mice

Dietary supplementation of clinically utilized PI3K p110α inhibitor extends the lifespan of male and female mice

  • Nat Aging. 2023 Feb;3(2):162-172. doi: 10.1038/s43587-022-00349-y.
C P Hedges 1 2,  B Shetty 1,  S C Broome 1,  C MacRae 1,  P Koutsifeli 3,  E J Buckels 2 4,  C MacIndoe 3,  J Boix 5,  T Tsiloulis 1,  B G Matthews 4,  S Sinha 6,  M Arendse 6,  J K Jaiswal 2 7,  K M Mellor 2 3,  A J R Hickey 8,  P R Shepherd 2 4,  T L Merry 9 10
Affiliations

Affiliations

  • 1 Discipline of Nutrition, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
  • 2 Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.
  • 3 Department of Physiology, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
  • 4 Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
  • 5 Centre for Brain Research, University of Auckland, Auckland, New Zealand.
  • 6 Department of Pathology, Waikato Hospital, Hamilton, New Zealand.
  • 7 Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand.
  • 8 Applied Surgery and Metabolism Laboratory, School of Biological Sciences, University of Auckland, Auckland, New Zealand.
  • 9 Discipline of Nutrition, School of Medical Sciences, University of Auckland, Auckland, New Zealand. [email protected].
  • 10 Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand. [email protected].
PMID: 37118113 DOI: 10.1038/s43587-022-00349-y
Abstract

Diminished Insulin and insulin-like growth factor-1 signaling extends the lifespan of invertebrates1-4; however, whether it is a feasible longevity target in mammals is less clear5-12. Clinically utilized therapeutics that target this pathway, such as small-molecule inhibitors of phosphoinositide 3-kinase p110α (PI3Ki), provide a translatable approach to studying the impact of these pathways on aging. Here, we provide evidence that dietary supplementation with the PI3Ki alpelisib from middle age extends the median and maximal lifespan of mice, an effect that was more pronounced in females. While long-term PI3Ki treatment was well tolerated and led to greater strength and balance, negative impacts on common human aging markers, including reductions in bone mass and mild hyperglycemia, were also evident. These results suggest that while pharmacological suppression of Insulin Receptor (IR)/insulin-like growth factor receptor (IGFR) targets could represent a promising approach to delaying some aspects of aging, caution should be taken in translation to humans.

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