The Science

INFLAMMAGING

Inflammaging is a state of chronic inflammation believed to develop with advancing age. Accumulation of senescent cells with a senescence-associated secretory phenotype (“SASP”) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Demographically, the world is rapidly growing older and more prone to inflammaging. All countries face major challenges to ensure that their health and social systems are ready to make the most of this demographic shift. According to the World Health Organization, in 2020, the number of people aged 60 years and older outnumbered children younger than 5 years. By 2030, 1 in 6 people in the world will be aged 60 years or over. In 2020, the population aged 60 years and over was estimated to be 1.4 billion. By 2050, the world’s population of people aged 60 years and older is expected to double to 2.1 billion.

As we grow older, a series of complex changes ripple through our immune system. Rising levels of inflammatory factors lead to unresolved, degenerative immune responses. Mounting evidence suggests that this inflammation undermines many bodily systems, accelerates biological aging and contributes to age-related diseases, such as cancer, cardiovascular disease, diabetes, and neurodegenerative disease.

The induction and retention of low-grade inflammation in an aging human body is mainly the result of the accumulation of non-proliferative but metabolically active senescent cells, which can also be caused by persistent activation of protein complexes, known as inflammasomes, in innate immune cells. These two elements share common mechanisms in promoting secretion of pro-inflammatory proteins and in many cases interact to drive senescence, and thus, inflammaging. Our novel approach is to reduce senescent cells and eliminate the pro-inflammatory factors they secrete systemically through multiple pathways. We believe our novel immunotherapeutic approach has the potential to fundamentally change the treatment of age-related diseases.

CELLULAR SENESCENCE

Cellular senescence is a biological condition resulting from the impact of stressors, such as chemotherapy, radiation, and pollutants, on human cells. These stressors reduce natural human cell cytotoxicity, leading to the accumulation of senescent cells and senescence-associated secretory phenotype (SASP). Considered harmful to neighboring cells, secreted SASP factors also activate a type of protein molecule called inflammasomes that accelerate the increasingly persistent cycle of inflammation.

As we age, senescent cells accumulate, and SASP factors increase, leading to low-grade, chronic inflammation and age-related diseases. At HCW Biologics, our proprietary immunotherapy platform rejuvenates the immune system, allowing it to reduce accumulated senescent cells and silence activated inflammasomes. This disrupts the link between aging and chronic disease.

ACTIVATED INFLAMMASOMES

As the first line of defense against infection or tissue injury, our innate immune system activates protein complexes called inflammasomes that initiate inflammatory responses. These activated inflammasomes persist as we age, even in the absence of infection, and regulate the release of pro-inflammatory factors. As inflammatory factor levels increase, this fuels a feedback cycle of inflammasome activation and leads to the persistent, low-grade body-wide inflammation associated with many age-related diseases.

Our mission at HCW Biologics is to lengthen healthspan by modulating the inflammasome pathway to reduce inflammation and associated age-related diseases.