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Updated: Aug 24, 2025

Techniques to Induce and Quantify Cellular Senescence
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Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

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Combining stem cell rejuvenation and senescence targeting to synergistically extend lifespan

Prameet Kaur1, Agimaa Otgonbaatar1, Anupriya Ramamoorthy1

  • 1Division of Science, Yale-NUS College, Singapore 138527, Singapore.

Aging
|October 26, 2022
PubMed

Insights

Combining stem cell rejuvenation and senescent cell removal significantly extends lifespan and improves health. This dual approach, targeting key aging mechanisms, offers synergistic anti-aging benefits for future therapies.

Area of Science:

  • Gerontology and regenerative medicine.
  • Cellular biology and aging research.

Background:

  • Biological age is a key risk factor for numerous human diseases, yet the underlying mechanisms are not fully understood.
  • Organismal aging is characterized by stem cell pool exhaustion and the accumulation of senescent cells, both contributing to age-related decline.
  • Independently, Yamanaka factor-induced pluripotency and senescent cell clearance can reverse aging aspects, indicating their roles as aging drivers.

Purpose of the Study:

  • To investigate the synergistic effects of combining transient cellular reprogramming (stem cell rejuvenation) with senescent cell removal on lifespan and healthspan.
  • To test the hypothesis that simultaneously targeting both stem cell exhaustion and cellular senescence maximizes anti-aging benefits.

Main Methods:

  • Transient expression of Yamanaka factors (Oct4, Klf4, Sox2, c-Myc; OKSM) for cellular reprogramming.
  • Targeted clearance of senescent cells.
  • Assessment of lifespan, intestinal stem cell protection, inflammation levels, and pro-stem cell signaling pathways.

Main Results:

  • OKSM expression alone extended lifespan.
  • The combination therapy protected the intestinal stem cell pool and reduced inflammation.
  • Both interventions synergistically improved overall health and extended lifespan.
  • Transient expression of both rejuvenation and senescent cell clearance proved most effective.

Conclusions:

  • Simultaneously targeting stem cell rejuvenation and senescent cell removal offers synergistic benefits for anti-aging.
  • Combination therapies hold significant potential for enhancing healthspan and lifespan.
  • Transient expression approaches suggest translatability to drug-based treatments for non-genetically tractable organisms.
Keywords:
agingsenescencestem cells

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