Catalysing ApoptoSENS

We are pleased to announce that the ApoptoSENS team led by Dr. Amit Sharma at the SRF Research Center has recently been granted a Catalyst award, courtesy of the Healthy Longevity Global Competition, to continue and expand their critical work on the interactions between senescent cells and natural killer (NK) cells.

The Healthy Longevity Global Competition, administered by the U.S. National Academy of Medicine (NAM) with support from Johnson & Johnson Innovation, will issue up to 24 Catalyst Awards per year between 2020 and 2022. Each Catalyst Award includes a $50,000 cash prize and travel costs to attend an annual Innovator Summit, beginning in summer 2021. The American Federation for Aging Research (AFAR) will collaborate with the NAM on the application and scientific review process.

The major consequence of unresolved DNA damage is a state of growth arrest termed cellular senescence. Although senescence can prevent mutated cells from transforming into cancer, it can also contribute to age-related disease – largely because senescent cells secrete pro-inflammatory factors, collectively known as the Senescence Associated Secretory Phenotype (SASP).

Strong correlations between the accumulation of senescent cells with increasing age and various negative outcomes, as well as the improvements in healthspan observed in several animal models upon their removal, have made senescent cells attractive targets for rejuvenation therapies. The ApoptoSENS strand of the SENS platform is dedicated to the development of those treatments.

Natural Killer (NK) cells are innate immune cells that surveil the body for precancerous cells and cells infected with viruses and other intracellular pathogens. Once the NK cells recognize a target (based on its display of activating and inhibitory receptors), they release cytotoxic proteins such as perforin and granzymes, which induce programmed death – apoptosis – in the target cells.

Recent reports indicate that NK cells can also selectively eliminate senescent cells in cell culture and animal models, opening up a new avenue to develop therapeutic interventions.

This field of research is still in its infancy, and there are several unanswered questions, such as:

  1. can senescent cells escape immune clearance by secreting or presenting decoy receptors, and
  2. how does immune senescence (NK cell aging) impact the cytotoxic potential of NK cells towards senescent cells?

Supported by the Catalyst Award, the ApoptoSENS team will now investigate whether the age-related loss of cytotoxic potential of NK cells toward senescent cells is reversible and, if so, whether and how this may provide routes for therapeutic intervention. If successful, this work will clear a major hurdle to realizing NK cell-based treatments for senescent cell elimination.

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