The gasotransmitters nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are a group of endogenous signalling molecules that play a central role in modulating many physiological and pathological processes, including age-related pathologies. Among their effects, it is well recognized that they induce smooth muscle relaxation, have anti-inflammatory and antifibrotic effects, and are involved in angiogenesis and modulation of oxidative stress. Furthermore, these effects could be potentiated or antagonized by each other at production levels, at downstream molecular targets, or direct interactions between themselves.

The aging process is a complex phenomenon that influences the effects and the efficacy of several signalling molecules including NO, CO, and H2S. A marked impairment in the NO-generating elements and in the NO-dependent biological effects have been linked with aging, to an extent that is proportional to the development of cardiovascular diseases. Conversely, plasmatic concentrations of H2S in humans decrease with aging, however, the relationship between H2S and aging and age-related pathologies is still largely unknown. HO-1, a precursor of CO, is a pathophysiological molecule activated by hemodynamic stress in response to elevated blood pressure and is upregulated in age-related pathologies such as atherosclerosis, preventing its development. The exposure to CO has been shown to improve pulmonary arterial hypertension in an eNOS/NO- dependent manner evidentiating that gasotransmitters interaction also exists in diseases.

This Special Issue aims to provide a deeper understanding of the molecular mechanisms of the above-mentioned transmitters and the mutual interactions of their signalling pathways in aging and age-related pathologies. This will allow the development of gasotransmitter-related donors and/or inhibitors as new therapeutic tools for the elderly. Original studies (basic, preclinical, and clinical), with an emphasis on molecular biology and molecular medicine of gasotransmitters, as well as reviews, are all welcome.

Potential topics include but are not limited to the following:

• NO, CO, and H2S interactions during aging and age-related pathologies
• Age-related differences in the synthesis and biological effects of gasotransmitters
• Sex differences in the gasotransmitter responses during the aging and age-related pathologies
• Oxidative stress and antioxidant enzymes and its relationship with gasotransmitters in the aging and age-related pathologies
• Therapeutic aspects of gasotransmitters and its potential to treat age-related pathologies
• Therapeutic use of novel gasotransmitter-related donors and/or inhibitors in age-related pathologies