Phase I Study to Assess the Safety and Immunogenicity of an Intradermal COVID-19 DNA Vaccine Administered Using a Pyro-Drive Jet Injector in Healthy Adults.

We conducted a nonrandomized, open-label phase I study to assess the safety and immunogenicity of an intradermal coronavirus disease 2019 (COVID-19) DNA vaccine (AG0302-COVID-19) administered using a pyro-drive jet injector at Osaka University Hospital between Yanagida November 2020 and December 2021. Twenty healthy volunteers, male or female, were enrolled in the low-dose (0.2 mg) or high-dose (0.

Alcohol drinking patterns have a positive association with cognitive function among older people: a cross-sectional study.

Background: The relationship between moderate alcohol drinking or other alcohol drinking patterns such as frequency, beverage type, and situation of drinking and cognitive function is not sufficiently clear in older people. The purpose of this study was to investigate the association between alcohol drinking patterns and cognitive function in community-dwelling Japanese people aged 75 and over.

Methods: This study was a cross-sectional design based on a prospective cohort study called the SONIC study.

Double Deletion of Angiotensin II Type 2 and Mas Receptors Accelerates Aging-Related Muscle Weakness in Male Mice.

Background The activation of AT2 (angiotensin II type 2 receptor ) and Mas receptor by angiotensin II and angiotensin-(1-7), respectively, is the primary process that counteracts activation of the canonical renin-angiotensin system (RAS). Although inhibition of canonical RAS could delay the progression of physiological aging, we recently reported that deletion of Mas had no impact on the aging process in mice. Here, we used male mice with a deletion of only AT2 or a double deletion of AT2 and Mas to clarify whether these receptors contribute to the aging process in a complementary manner, primarily by focusing on aging-related muscle weakness.

RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane.

The receptor for advanced glycation end-products (RAGE) and the G protein-coupled angiotensin II (AngII) type I receptor (AT1) play a central role in cardiovascular diseases. It was recently reported that RAGE modifies AngII-mediated AT1 activation via the membrane oligomeric complex of the two receptors. In this study, we investigated the presence of the different directional crosstalk in this phenomenon, that is, the RAGE/AT1 complex plays a role in the signal transduction pathway of RAGE ligands.

The endocytosis of oxidized LDL via the activation of the angiotensin II type 1 receptor.

Arrestin-dependent activation of a G-protein-coupled receptor (GPCR) triggers endocytotic internalization of the receptor complex. We analyzed the interaction between the pattern recognition receptor (PRR) lectin-like oxidized low-density lipoprotein (oxLDL) receptor (LOX-1) and the GPCR angiotensin II type 1 receptor (AT1) to report a hitherto unidentified mechanism whereby internalization of the GPCR mediates cellular endocytosis of the PRR ligand. Using genetically modified Chinese hamster ovary cells, we found that oxLDL activates Gαi but not the Gαq pathway of AT1 in the presence of LOX-1.

A pressor dose of angiotensin II has no influence on the angiotensin-converting enzyme 2 and other molecules associated with SARS-CoV-2 infection in mice.

In the early phase of the Coronavirus disease 2019 (COVID-19) pandemic, it was postulated that the renin-angiotensin-system inhibitors (RASi) increase the infection risk. This was primarily based on numerous reports, which stated that the RASi could increase the organ Angiotensin-converting enzyme 2 (ACE2), the receptor of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in rodents. RASi can theoretically antagonize the potential influence of angiotensin II (Ang II) on ACE2.

Angiotensin 1-7 alleviates aging-associated muscle weakness and bone loss, but is not associated with accelerated aging in ACE2-knockout mice.

The angiotensin-converting enzyme 2 (ACE2)-angiotensin 1-7 (A1-7)-A1-7 receptor (Mas) axis plays a protective role in the renin-angiotensin system (RAS). We recently found that ACE2 knockout (ACE2KO) mice exhibit earlier aging-associated muscle weakness, and that A1-7 alleviates muscle weakness in aging mice. In the present study, we investigated the role of the A1-7-Mas pathway in the effect of ACE2 on physiological aging.

Serum albumin/globulin ratio is associated with cognitive function in community-dwelling older people: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study.

Aim: The objective of this study was to clarify the relationship between cognitive function and the serum albumin/globulin ratio (A/G ratio) in community-dwelling Japanese older adults.

Methods: Randomly extracted residents in both urban and rural parts of Japan were enrolled in this study. A total of 1827 participants with a mean age of 70 or 80 years were recruited.

Association between long-term care and chronic and lifestyle-related disease modified by social profiles in community-dwelling people aged 80 and 90; SONIC study.

Background: Chronic and lifestyle-related diseases and social status were reported to be associated with long-term care (LTC). The social factors should be treated as social sub-groups of which characteristics show social profiles. However, few previous studies considered that.

A gene single nucleotide polymorphism is associated with the onset of stroke and plasma klotho concentration.

protects against development of multiple age-related disorders, including cardiovascular diseases. We assessed whether a human single nucleotide polymorphism (SNP) rs650439 is associated with the onset of stroke in hypertensive patients and plasma klotho concentration in the general population. Five hundred and twenty-three patients with hypertension were analyzed for both the presence of rs650439 and onset of stroke.

Pathophysiological significance of cylindromatosis in the vascular endothelium and macrophages for the initiation of age-related atherogenesis.

Cardiovascular disease is one of the leading causes of death in the elderly, and novel therapeutic targets against atherogenesis are urgent. The initiation of atherosclerotic changes of monocyte adhesion on the vascular endothelium and subsequent foam cell formation are noteworthy pathophysiologies when searching for strategies to prevent the progression of age-related atherosclerosis. We report the significance of the deubiquitinating enzyme cylindromatosis (CYLD) in vascular remodeling by interference with inflammatory responses regulated by NF-κB signaling.

Angiotensin-converting enzyme 2 deficiency accelerates and angiotensin 1-7 restores age-related muscle weakness in mice.

Background: A pharmacologic strategy for age-related muscle weakness is desired to improve mortality and disability in the elderly. Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin II into angiotensin 1-7, a peptide known to protect against acute and chronic skeletal muscle injury in rodents. Since physiological aging induces muscle weakness via mechanisms distinct from other muscle disorders, the role of ACE2-angiotensin 1-7 in age-related muscle weakness remains undetermined.

High plasma adiponectin levels are associated with frailty in a general old-old population: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study.

Aim: The objective of the present study was to investigate the association between frailty and plasma adiponectin levels in a general population of Japanese older adults.

Methods: The volunteer older adults, aged approximately 83 years, were recruited randomly from a general population in the Japanese Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study. We used the modified Cardiovascular Health Study criteria to assess the frailty status of the study participants.

Longitudinal association of hypertension and diabetes mellitus with cognitive functioning in a general 70-year-old population: the SONIC study.

Both hypertension and diabetes in middle-aged individuals have been suggested to be predictive indicators of cognitive decline. However, the association of hypertension, diabetes and their combination with cognitive functioning is still controversial in older people. The purpose of this study was to investigate the association between cognitive decline and hypertension, diabetes, and their combination in 70-year-old people based on a 3-year longitudinal analysis.

Modified forelimb grip strength test detects aging-associated physiological decline in skeletal muscle function in male mice.

The conventional forelimb grip strength test is a widely used method to assess skeletal muscle function in rodents; in this study, we modified this method to improve its variability and consistency. The modified test had lower variability among trials and days than the conventional test in young C57BL6 mice, especially by improving the variabilities in male. The modified test was more sensitive than the conventional test to detect a difference in motor function between female and male mice, or between young and old male mice.

Differences in the association between high blood pressure and cognitive functioning among the general Japanese population aged 70 and 80 years: The SONIC study.

High blood pressure in middle age (up to 64 years) has been proposed as a predictive indicator of dementia. However, the association between hypertension and the cognitive functioning is controversial in older age groups. The aim of this study was to investigate this association in 70-80-year-old participants in the Japanese study of Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC).