Exploring Synergies between Senolysis and Stem Cell Therapy

  • Research Info
  • Team Members
  • Photos
  • Funding
  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding

The accumulation of damaged/senescent cells in the body with time is a hall mark of aging. These cells are believed to play a key role in the onset and/or progression of various aging-associated diseases. More generally, the decreased regenerative ability of transplanted stem cells in older recipients may also be partly attributable to the presence of a high level of senescent cells.

Many factors produced by senescent cells – including proinflammatory cytokines, profibrotic molecules and damaging agents such as labile iron and reactive aldehydes – are known to disrupt the function of normal cells and cause organ function to decline. The hostile environment created by senescent cells is likely to impair the ability of transplanted stem cells to home in on target tissues, mature and restore tissue function.  Therefore, prior removal of senescent cells will likely enhance the effectiveness of stem cell transplantation therapies.

In recent years, two major observations in the longevity field have been made:

  • The use of senolytics to remove senescent cells significantly improved health and lifespan in mice and as might be expected, this approach enhanced the repopulation ability of endogenous stem cells1.
  • Stem cell transplantation has demonstrated beneficial effects in reducing aging-associated functional decline in both mice and humans, and extended lifespans in mice2,3.

The SenoStem project will test the hypothesis that prior removal of senescent cells by senolytics will create a more favorable niche for stem cells to engraft, and thus enhance their regenerative effect in older recipients. The overall aim is to determine whether these two different lifespan-extending interventions can act synergistically.

The first phase of this project will be to carryout in vitro and in vivo studies in order to identify the most  effective and safe senolytic from a list of established and in-house candidates.

The second phase of the project will assess the effectiveness of a combination therapy in which mice are treated with a lead senolytic identified in phase I, followed by transplantation of stem cells. We expect that the combination therapy will be more effective than either the senolytic or stem cell treatment alone.

Senescent cells impair the function of healthy stem cells in aged bodies. Accordingly, prior treatment with a senolytic drug is expected to result in superior function of transplanted stem cells.

References

  1. Chang J, et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med. 2016 Jan;22(1):78-83. doi: 10.1038/nm.4010. PMID: 26657143
  2. Kovina MV, et al. Extension of Maximal Lifespan and High Bone Marrow Chimerism After Nonmyeloablative Syngeneic Transplantation of Bone Marrow From Young to Old Mice. Front Genet. 2019 Apr 12;10:310. doi: 10.3389/fgene.2019.00310. PMID: 31031800
  3. Guderyon MJ, et al. Mobilization-based transplantation of young-donor hematopoietic stem cells extends lifespan in mice. Aging Cell. 2020 Mar;19(3):e13110. doi: 10.1111/acel.13110. PMID: 32012439

Team Members

We’re Hiring!

Please visit the Work With Us page to learn about available positions.

Principal Investigator

Hadi Rebbaa

Abdelhadi Rebbaa, PhD

Research Staff

ElenaMagay

Elena Magay, PhD

Oliver Frost

Oliver Frost (PhD Student)

Postbaccalaureate Fellows

Summer Scholars

Lab Alumni

Publications

Photos

Resources

Funding

To support our work please consider making a donation to SENS Research Foundation!

This project is funded by:

Job Opportunity: Educational Coordinator

Job Type: Full-time
Title: Educational Coordinator
Salary: Pay is salaried, commensurate with job title and responsibilities.

Qualifications:

  • Bachelor’s degree in biology and/or education, or relevant field (Required)
  • 1+ years of teaching experience (Preferred)

SENS Research Foundation (SRF) is hiring an Educational Coordinator for our foundation located in Mountain View, CA. SRF is an exciting, cutting edge non-profit dedicated to transforming the way the world researches and treats age-related disease. Learn more about us at www.sens.org

Qualified candidates will have a minimum of a bachelor’s degree in biology and/or education (or relevant field). Other qualifications or skills should include:

  • Attention to detail
  • Exceptional communication skills
  • Capacity for scientific literacy and passion for our mission
  • Extremely thorough and organized
  • Flexible and willing to learn new skills
  • Proficiency in Microsoft Excel
  • 1+ years of teaching experience

This is a full-time position and will be remote to start – however that may change post-COVID concerns. We are willing to be flexible for the right candidate. Duties will include:

  • Coordinating between students, researchers, and admin staff
  • Coordinating between SRF and host institutions
  • Facilitating and organizing seminars and presentations
  • Organizing application materials and screening applications for academic programs
  • Managing logistical inquiries from applicants
  • Managing schedules

We offer an excellent benefits package including paid vacation and sick leave, fully covered health insurance (inclusive of dependents), an FSA program, and a company matched 401(k) plan. SENS Research Foundation is an equal opportunity employer.

The position is available now and will be filled as soon as the qualified candidate is found. Salary is commensurate with job title.

TO APPLY:

Interested candidates should apply by submitting their resumes and cover letters to [email protected]

COVID-19 considerations:

All employees are to follow COVID restrictions, which will lighten as our workplace is vaccinated. All employees are expected to wear PPE. Vaccinating is strongly encouraged.

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