The Missing Link Between Senescence and Body-Wide Aging

The Problem

Senescent, or old, cells drive diseases of aging in tissues far removed from where the damaged cells are located. It is assumed that these effects result from factors that senescent cells release (the “SASP”) being carried by the blood, but this hasn’t been proven in studies. If senescent cells don’t raise the level of SASP in blood, it’s unknown how they cause the damaging effects of aged blood or explain the whole-body benefits when senescent cells are removed.

The Goal

Looking at how the SASP has been defined – as mostly proteins that don’t correlate well to the volume of senescent cells – Sharma’s lab has identified other substances within SASP that have not previously been shown and could explain the link between the SASP and diseases of aging. 

The Status

These substances have been shown to cause healthy cells to become senescent themselves and have been identified in aged blood, but not young. This is a possible new driver of the diseases of aging and a new target for therapies to prevent them. 

Identifying the Basis of Deleterious Systemic Effects of Senescent Cells

A key phenomenon that links senescent cells (SEN) to disease is secondary senescence, in which factors secreted by senescent cells (the SASP) drive senescence in distal nonsenescent cells. However, while circulating levels of some known SASP constituents rise with age, there is no clear correlation between an aged organism’s SEN burden and its level of specific classical SASP factors (cytokines, proteases, and growth factors) in circulation. This suggests that while classical SASP factors may exert deleterious effects on adjacent nonsenescent cells, some other factor(s) are responsible for propagating secondary senescence and other distal harms of SEN.

The Sharma lab has identified a novel SASP constituent that may be the missing link between SEN and their systemic aging effects. They identified high levels of a previously-unknown substance in SEN, not found in nonsenescent cell conditioned medium (CM). The fraction of SEN CM enriched in these substances causes nonsenescent cells to become senescent, whereas neither the SEN CM fraction – that is low in these substances but contains the classical SASP factors – nor the CM of nonsenescent cells, exert this effect. Notably, blood from aging humans contains high levels of substances that resemble the newly-identified material in SEN CM, while blood from young subjects contains very low levels. This supports the translatability of the in vitro finding and its candidacy as the mediator of the distal effects of SEN. Biotechnology already validated against other damage-repair targets is anticipated to deplete the new SASP constituent from the blood without impacting physiological substrates, suggesting a strategy to decouple SEN burden from its downstream consequences.

Team Members

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

Dr. Amit Sharma

Dr. Amit Sharma

Principal Investigator

Dr. Amit Sharma was awarded a Master’s degree in Biomedical Sciences from Delhi University, India.  He received his PhD in 2009 in Biotechnology from University of Pune for his work demonstrating microRNA regulation of cytokines involved in allergic inflammation in mice model. Dr. Sharma’s postdoctoral research at the Buck Institute, Novato California involved investigating novel molecular regulatory pathways involved in genotoxic stress and cellular senescence in invertebrate and mammalian models.

Dr. Sharma is the SENS Research Foundation Group Lead in the Senescence Immunology Research Group. His research focus involves studying how aging and senescence affects the immune system and his research group will also investigate strategies to harness the immune system in mitigating deleterious effects of senescent cells with translational focus.


Annual Budget
150,000 USD

Intro to SENS:

Intramural Research:

Extramural Research:

Use of this Web site constitutes acceptance of the Terms of Use and Privacy Policy.

© 2024 SENS Research Foundation – ALL RIGHTS RESERVED

Thank you for Subscribing to the SENS Research Foundation Newsletter.

You can also


You can