Photobiomodulation therapy mitigates cardiovascular aging and improves survival.

BACKGROUND: Photobiomodulation (PBM) therapy, a form of low-dose light therapy, has been noted to be effective in several age-associated chronic diseases such as hypertension and atherosclerosis. Here, we examined the effects of PBM therapy on age-associated cardiovascular changes in a mouse model of accelerated cardiac aging. METHODS: Fourteen months old Adenylyl cyclase type VIII (AC8) overexpressing transgenic mice (n = 8) and their wild-type (WT) littermates (n = 8) were treated with daily exposure to Near-Infrared Light (850 nm) at 25 mW/cm2 for 2 min each weekday for a total dose of 1 Einstein (4.5 p.J/cm2 or fluence 3 J/cm2 ) and compared to untreated controls over an 8-month period. PBM therapy was administered for 3.5 months (Early Treatment period), paused, due to Covid-19 restrictions for the following 3 months, and restarted again for 1.5 months. Serial echocardiography and gait analyses were performed at monthly intervals, and serum TGF-ß1 levels were assessed following sacrifice. RESULTS: During the Early Treatment period PBM treatments: reduced the age-associated increases in left ventricular (LV) mass in both genotypes (p = 0.0003), reduced the LV end-diastolic volume (EDV) in AC8 (p = 0.04); and reduced the left atrial dimension in both genotypes (p = 0.02). PBM treatments substantially increased the LV ejection fraction (p = 0.03), reduced the aortic wall stiffness (p = 0.001), and improved gait symmetry, an index of neuro-muscular coordination (p = 0.005). The effects of PBM treatments, measured following the pause, persisted. Total TGF-ß1 levels were significantly increased in circulation (serum) in AC8 following PBM treatments (p = 0.01). We observed a striking increase in cumulative survival in PBM-treated AC8 mice (100%; p = 0.01) compared to untreated AC8 mice (43%). CONCLUSION: PBM treatment mitigated age-associated cardiovascular remodeling and reduced cardiac function, improved neuromuscular coordination, and increased longevity in an experimental animal model. These responses correlate with increased TGF-ß1 in circulation. Future mechanistic and dose optimization studies are necessary to assess these anti-aging effects of PBM, and validation in future controlled human studies is required for effective clinical translation.

Age-associated difference in circulating ACE2, the gateway for SARS-COV-2, in humans: results from the InCHIANTI study.

Levels of angiotensin-converting enzyme 2 (ACE2), the gateway for COVID-19 virus into the cells, have been implicated in worse COVID-19 outcomes associated with aging and cardiovascular disease (CVD). Data on age-associated differences in circulating ACE2 levels in humans and the role of CVD and medications is limited. We analyzed data from 967 participants of the InCHIANTI study, a community-dwelling cohort in the Chianti region, Italy. Relative abundance of ACE2 in plasma was assessed using a proteomics platform. CVD diagnoses, use of renin-angiotensin-aldosterone system (RAAS) antagonists: ACEi, ARBs, and aldosterone antagonists, were ascertained. Multiple linear analyses were performed to examine the independent association of ACE2 with age, CVD, and RAAS antagonist use. Age was independently associated with lower log (ACE2) in persons aged ≥ 55 years (STD ß = - 0.12, p = 0.0002). ACEi treatment was also independently associated with significantly lower ACE2 levels, and ACE2 was inversely associated with weight, and positively associated with peripheral artery disease (PAD) status. There was a trend toward higher circulating ACE2 levels in hypertensive individuals, but it did not reach statistical significance. In a stratified analysis, the association between log (ACE2) and log (IL-6) was more evidenced in participants with PAD. Circulating ACE2 levels demonstrate curvilinear association with age, with older individuals beyond the sixth decade age having lower levels. ACEi was associated with greater circulating ACE2 levels. Interestingly, ACE2 was elevated in PAD and positively associated with inflammatory markers, suggesting compensatory upregulation in the setting of chronic inflammation. Further studies are needed to comprehensively characterize RAAS components with aging and disease, and assess its prognostic role in predicting COVID-19 outcomes.

Aging- and gender-related modulation of RAAS: potential implications in COVID-19 disease.

Coronavirus disease 2019 (COVID-19) is a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is frequently characterized by a marked inflammatory response with severe pneumonia and respiratory failure associated with multiorgan involvement. Some risk factors predispose patients to develop a more severe infection and to an increased mortality; among them, advanced age and male gender have been identified as major and independent risk factors for COVID-19 poor outcome. The renin-angiotensin-aldosterone system (RAAS) is strictly involved in COVID-19 because angiotensin converting enzyme 2 (ACE2) is the host receptor for SARS-CoV-2 and also converts pro-inflammatory angiotensin (Ang) II into anti-inflammatory Ang(1-7). In this review, we have addressed the effect of aging and gender on RAAS with emphasis on ACE2, pro-inflammatory Ang II/Ang II receptor 1 axis and anti-inflammatory Ang(1-7)/Mas receptor axis.