What Would You Do If You Had More Time?

Maximizing the Human Healthspan through Environmental and Lifestyle Factors with Influences on Associated Diseases through Genetics and Epigenetics, utilizing Statistical Models and Gene Expression Data

Abstract

In humans, the gap between healthspan, “the period of life spent without disease,” and lifespan has only widened in recent years, resulting in us spending an ever-increasing part of our lives being sick and in need of care. Although there has been a recent increase in aging-related research, the specific influences environmental and lifestyle factors play on healthspans through physiology, as well as genetics and epigenetics, remains unclear due to gaps in literature.

Consequently, this study aimed to 1) determine the most significant environmental and lifestyle factors through statistical modeling of humans' healthspans, 2) identify genes that have a potential role in, or are affected by, the most significant environment and lifestyle factors and aging, and 3) elucidate the potential roles, related signaling pathways, and functions of the selected, identified genes, which were Pellino Homolog 2 (PELI2) and HomeoboxB4 (HOXB4), associated to aging-associated diseases, specifically non-small cell lung cancer (NSCLC). This study is the first to 1) assess PELI2’s potential roles in lung cancer and 2) suggest that HOXB4 and PELI2 have a potential role in lung squamous cell carcinoma (LUSC) and lung cancer, respectively.

Smoking, obesity, and air pollution were established to have the most significant impact on the healthspan and lifespan. The downregulation of PELI2 and HOXB4, potentially activated by aging, smoking, air pollution, and obesity, and the percent survival of NSCLC were closely correlated, especially in LUAD and LUSC, suggesting that PELI2 and HOXB4 may perform a pivotal role in the tumorigenesis of NSCLC, interrupting the healthspan.