Some reports indicate that the essential cellular components (various organelles) promote the “controlled” formation of prooxidants and consequently trigger pro-inflammatory markers (putative biosignaling cascade associated with innate immunity) to reduce pathogen-mediated injury/insult, decrease the risk for tumor/malignancy which can then significantly augment the lifespan of animals and humans. Interestingly, numerous scientific evidence has become apparent associating mitochondrial impairment with aberrant innate immune responses.  The heart, a vital organ in the body, plays an important physiological role in regulating organismal lifespan.  In addition, aging is associated with a gradual and continual decrease in cardiac functions.  There are not many valid in vitro/ in vivo chemically-induced or genetic models that exist to assess the biosignaling mechanisms associated with aging.  Ames dwarf mice (exhibit a point mutation in the prophet of pit-1 gene) are phenotypically distinguished by small body size and delayed puberty (lacking growth hormone, thyrotropin, and prolactin), live considerably longer, 49–64%, than wild-type animals from the same strain.  However, the cellular biosignaling markers associated with innate immunity and protease activity in the heart of the Ames dwarf mice and their age-matched controls are unknown.  Hence, in this study, the markers of oxidative stress (Reactive Oxygen Species-ROS), inflammation (Interleukin Converting Enzyme-1 (ICE-1) and cyclooxygenase activities (COX)), apoptosis (serine protease, caspase-3,8,9 activities), and mitochondrial NADH content were measured in the Ames mice and its age-matched wild type controls (6 and 20-months old).  Statistical analysis was performed using Prism-V software (La Jolla, CA, USA).  The noteworthy findings in the study are that the NADH content, the serine protease, ICE-I, and COX activities were significantly increased in the Ames dwarf mice.  Thus, the current study emphasizes the critical functions of growth hormone deficiency in modulating oxidative stress as well as innate immune responses in the heart.  Furthermore, elucidating the signaling interplay of prooxidants (ROS), mitochondrial NADH content, apoptotic and inflammasome pathways in the heart of the growth hormone-deficient mice improved our understanding and knowledge regarding the concepts related to aging.