ACE
Angiotensin-converting enzyme precursor (EC 3.2.1.-) (EC 3.4.15.1) (ACE) (Dipeptidyl carboxypeptidase I) (Kininase II) (CD143 antigen) [Contains: Angiotensin-converting enzyme, soluble form] [DCP] [DCP1]
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Aging increases risk for ischemic vascular diseases. Bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) are known to stimulate vascular regeneration. Activation of either the Mas receptor (MasR) by angiotensin-(1-7) (Ang-(1-7)) or angiotensin-converting enzyme-2 (ACE2) stimulates vasoreparative functions in HSPCs. This study tested if aging is associated with decreased ACE2 expression in HSPCs and if Ang-(1-7) restores vasoreparative functions. Flow cytometric enumeration of Lin CD45 CD34 cells was carried out in peripheral blood of male or female individuals (22-83 years of age). Activity of ACE2 or the classical angiotensin-converting enzyme (ACE) was determined in lysates of HSPCs. Lin Sca-1 cKit (LSK) cells were isolated from young (3-5 months) or old (20-22 months) mice, and migration and proliferation were evaluated. Old mice were treated with Ang-(1-7), and mobilization of HSPCs was determined following ischemia induced by femoral ligation. A laser Doppler blood flow meter was used to determine blood flow. Aging was associated with decreased number (Spearman r = - 0.598, P < 0.0001, n = 56), decreased ACE2 (r = - 0.677, P < 0.0004), and increased ACE activity (r = 0.872, P < 0.0001) (n = 23) in HSPCs. Migration or proliferation of LSK cells in basal or in response to stromal-derived factor-1α in old cells is attenuated compared to young, and these dysfunctions were reversed by Ang-(1-7). Ischemia increased the number of circulating LSK cells in young mice, and blood flow to ischemic areas was recovered. These responses were impaired in old mice but were restored by treatment with Ang-(1-7). These results suggest that activation of ACE2 or MasR would be a promising approach for enhancing ischemic vascular repair in aging.
Keywords
- ACE2
- Aging
- Angiotensin-(1-7)
- Hematopoietic stem/progenitor cells
- Ischemia
Elite athletes are reported to possess longer telomeres than their less active counterparts. ACE gene (Insertion/Deletion) polymorphism has been previously associated with elite athletic performance, with the deletion (D) variant appearing more frequently in short distance swimmers. Additionally, the D allele has been reported to have a negative effect on telomere length. The aim of this study was to investigate the telomere length of elite swimmers and its potential association with ACE genotype. Telomere length was measured by real-time quantitative PCR and ACE I/D genotypes analysed by standard PCR and electrophoresis in 51 young elite swimmers and 56 controls. Elite swimmers displayed shorter telomeres than controls (1.043 ± 0.127 vs 1.128 ± 0.177, p = 0.006). When split by sex, only elite female swimmers showed significantly shorter telomeres than their recreationally active counterparts (p = 0.019). ACE genotype distribution and allelic frequency did not differ between elite swimmers and controls, or by event distance among elite swimmers only. No association was observed between telomere length and ACE genotype in the whole cohort. Elite swimmers possessed shorter telomeres than recreationally active controls. Our findings suggesting a negative effect of high-level swimming competition and/or training on telomere length and subsequent biological aging, particularly in females. However, this significant difference in telomere length does not appear to be attributed to the D allele as we report a lack of association between telomere length and ACE genotype frequency in elite swimmers and controls.
Keywords
- Aging
- Athlete
- Exercise
- Genetics
Coronavirus Disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily targets the human respiratory system and may lead to severe pneumonia and ultimately death. Mortality rate is particurlarly high among people beyond the sixth decade of life with cardiovascular and metabolic diseases. The discovery that the SARS-CoV-2 uses the renin-angiotensin system (RAS) component ACE2 as a receptor to invade host epithelial cells and cause organs damage resulted in a debate regarding the role of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) therapies during COVID-19 pandemic. Some authors proposed the discontinuation of ACEIs and ARBs for cardiovascular, kidney, and metabolic diseases, while expert opinions have discouraged that due to limited empirical evidence of their negative effect on COVID-19 outcomes, and that withdrawing treatment may contribute to clinical decompensation in high-risk patients. Moreover, as cardiovascular and metabolic diseases are associated with neurodegenerative and psychiatric disorders, especially among older adults, a critical appraisal of the potential positive effects of ACEIs and ARBs is highly needed. Herein, we aim to discuss the conundrum of ACEIs and ARBs use in high-risk patients for COVID-19, and their potential protective role on the development and/or progression of geriatric neuropsychiatric disorders.
Keywords
- ACE2
- ACEIs
- ARBs
- COVID-19
- RAS
- SARS-CoV-2
- geriatrics
- neuropsychiatric disorders
Polycystic ovary syndrome, the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenemia, obesity, insulin resistance, and elevated blood pressure. However, few studies have focused on the consequences of pregnancy on postmenopausal cardiovascular disease and hypertension in polycystic ovary syndrome women. In hyperandrogenemic female (HAF) rats, the hypothesis was tested that previous pregnancy protects against age-related hypertension. Rats were implanted with dihydrotestosterone (7.5 mg/90 days, beginning at 4 weeks and continued throughout life) or placebo pellets (controls), became pregnant at 10 to 15 weeks, and pups were weaned at postnatal day 21. Dams and virgins were then aged to 10 months (still estrous cycling) or 16 months (postcycling). Although numbers of offspring per litter were similar for HAF and control dams, birth weights were lower in HAF offspring. At 10 months of age, there were no differences in blood pressure, proteinuria, nitrate/nitrite excretion, or body composition in previously pregnant HAF versus virgin HAF. However, by 16 months of age, despite no differences in dihydrotestosterone, fat mass/or lean mass/body weight, previously pregnant HAF had significantly lower blood pressure and proteinuria, higher nitrate/nitrite excretion, with increased intrarenal mRNA expression of endothelin B receptor and eNOS (endothelial nitric oxide synthase), and decreased ACE (angiotensin-converting enzyme), AT1aR (angiotensin 1a receptor), and endothelin A receptor than virgin HAF. Thus, pregnancy protects HAF rats against age-related hypertension, and the mechanism(s) may be due to differential regulation of the nitric oxide, endothelin, and renin-angiotensin systems. These data suggest that polycystic ovary syndrome women who have experienced uncomplicated pregnancy may be protected from postmenopausal hypertension.
Keywords
- aging
- endothelin
- menopause
- nitric oxide
- renin-angiotensin system
The heart failure (HF)-syndrome is associated with neuro-hormonal activation, chronic kidney disease (CKD), inflammation and alterations in the phosphorus-metabolism, all of which are involved in regulation of mineral bone density. However, the role of HF as an independent factor associated with metabolic bone disease (MBD) remains unclear. HF-patients undergoing dual X-ray absorptiometry (DEXA) were matched in a 1:2 fashion against age and gender matched controls without HF, to determine the proportion of osteoporosis (T-score < -2.5). HF-status was tested against known predictors of MBD. Correlation analysis and Z-score analysis were used to assess the impact of HF on age-related bone demineralisation. A total of 190 HF-patients (age = 80 ± 10 years, female = 61%) were age and gender matched to 380 controls. HF-patients had a higher proportion of osteoporosis (26 vs 17%; [i]p[/i] = .007). HF patients had a lower averaged mineral bone density expressed in g/cm ([i]p[/i] = .030), T-scores ([i]p[/i] = .001) and Z-scores ([i]p[/i] < .001). After adjusting for the individual osteoporosis risk-factors of the FRAX-score, difference in baseline features, kidney function and phosphorus-metabolism alterations, heart failure remained independently associated with a lower averaged T-score (Adjusted [i]β[/i] = -0.189; [i]p[/i] = .017). Heart failure was associated with an accelerated age-related decline in mineral bone density ([i]p[/i] = .0418). Therapies with ACE-I or ARBs and beta-blockers associated with ameliorated bone demineralisation ([i]p[/i] = .023, respectively [i]p[/i] = .029), while loop diuretic associated with worsened bone demineralization ([i]p[/i] < .001). Heart failure independently associates with MBD and higher prevalence of osteoporosis. Heart failure aggravates the aged related loss in mineral bone density while treatment with neuro-hormonal blockers seemed to ameliorate this finding.
Keywords
- Heart failure
- comorbidities
- geriatrics
- metabolic bone disease
- osteoporosis
Heart failure (HF) is often managed by geriatricians. Few data are available on their knowledge and attitudes about this condition. To compare perceptions and knowledge on HF of specialists/fellows in geriatrics working in Italy. This nation-wide survey carried out by the Italian Society of Gerontology and Geriatrics in May-June 2019 enrolled 283 specialists/fellows in geriatrics in Italy. Results were stratified by qualification (specialist/fellow) and performance (lower/higher quartile of correct answers). About half (55.5%) of the participants worked in acute care wards, 190 were residents, and 93 specialists. The overall proportion of correct answers was 70.8%, with no differences between specialists and fellows. There was a poor knowledge, with no differences between groups, about the target doses of ACE-inhibitors (36% of correct answers), the pharmacological treatment of HF with preserved ejection fraction (HFpEF) (37% of correct answers), and the inotropes indicated in acute HF (35% of correct answers). Compared to specialists, fellows performed better on indication (88% vs 76%, P = 0.019) and mechanism of action (93% vs 84%, P = 0.023) of sacubitril/valsartan, and on therapeutic indications of patients with atrial fibrillation (92% vs 75%, P < 0.001). Globally, there was a good knowledge of the latest guidelines on the diagnosis and management of HF. However, for some important topics, such as HFpEF, that is the most common HF manifestation in older adults, the observed performance was relatively poor, indicating the need for focused educational campaigns.
MeSH Terms
- Aged
- Geriatrics
- Heart Failure
- Humans
- Italy
- Specialization
- Stroke Volume
- Surveys and Questionnaires
Keywords
- Aged, 65 years or over
- Care survey
- Health
- Heart failure
Some studies have suggested that the insertion(I)/deletion(D) polymorphism of the Angiotensin-Converting Enzyme (ACE) gene may be associated with human longevity, especially in centenarians. However, this association is still controversial. Besides, there have been no studies in Peruvians. To describe the age distribution of the ACE polymorphism in a convenience sample of Peruvian older people. This was a cross-sectional study in 104 Geriatric Day Hospital patients in Lima, Perú. The ACE polymorphism was determined in all patients. For the purpose of association with age, the sample was divided into four categories: young (< 65), youngest-old (65-74), middle-old (75-84) and oldest-old (85 or more). The distribution of genotype frequencies was consistent with a population in Hardy-Weinberg equilibrium ([i]p[/i] = 0.62). The number (%) of D/D, I/D and I/I genotypes in the young was 2 (14.3%), 3 (21.4%) and 9 (64.3%), respectively; in youngest-old: 4 (11.4%), 15 (42.9%) and 16 (45.7%); in middle-old: 6 (12.2%), 20 (40.8%) and 23 (46.9%); and in oldest-old: 0 (0.0%), 4 (66.7%) and 2 (33.3%). A chi-square analysis showed no significant differences in genotype distribution between age groups ([i]p[/i] = 0.647). No significant age differences were found in the distribution of the ACE polymorphism in this sample. Further studies with greater statistical power are recommended.
MeSH Terms
- Aged
- Aged, 80 and over
- Cross-Sectional Studies
- Female
- Genetic Variation
- Humans
- Longevity
- Male
- Middle Aged
- Peptidyl-Dipeptidase A
- Peru
- Polymorphism, Genetic
Keywords
- ACE gene
- Longevity
- Perú
- ageing
COVID-19, also known as SARS-CoV-2, is a new emerging zoonotic corona virus of the SARS (Severe Acute Respiratory Syndrome) and the MERS (Middle East Respiratory Syndrome) family. COVID-19 originated in China and spread world-wide, resulting in the pandemic of 2020. For some reason, COVID-19 shows a considerably higher mortality rate in patients with advanced chronological age. This begs the question as to whether there is a functional association between COVID-19 infection and the process of chronological aging. Two host receptors have been proposed for COVID-19. One is CD26 and the other is ACE-2 (angiotensin-converting enzyme 2). Interestingly, both CD26 and the angiotensin system show associations with senescence. Similarly, two proposed therapeutics for the treatment of COVID-19 infection are Azithromycin and Quercetin, both drugs with significant senolytic activity. Also, Chloroquine-related compounds inhibit the induction of the well-known senescence marker, Beta-galactosidase. Other anti-aging drugs should also be considered, such as Rapamycin and Doxycycline, as they behave as inhibitors of protein synthesis, blocking both SASP and viral replication. Therefore, we wish to speculate that the fight against COVID-19 disease should involve testing the hypothesis that senolytics and other anti-aging drugs may have a prominent role in preventing the transmission of the virus, as well as aid in its treatment. Thus, we propose that new clinical trials may be warranted, as several senolytic and anti-aging therapeutics are existing FDA-approved drugs, with excellent safety profiles, and would be readily available for drug repurposing efforts. As Azithromycin and Doxycycline are both commonly used antibiotics that inhibit viral replication and IL-6 production, we may want to consider this general class of antibiotics that functionally inhibits cellular protein synthesis as a side-effect, for the treatment and prevention of COVID-19 disease.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Angiotensin-Converting Enzyme 2
- Antiviral Agents
- Azithromycin
- Betacoronavirus
- COVID-19
- Coronavirus Infections
- Dipeptidyl Peptidase 4
- Humans
- Hydroxychloroquine
- Pandemics
- Peptidyl-Dipeptidase A
- Pneumonia, Viral
- Quercetin
- Receptors, Virus
- SARS-CoV-2
Keywords
- Azithromycin
- COVID-19
- Doxycycline
- Hydroxy-chloroquine
- Quercetin
- Rapamycin
- aging
- antibiotic
- corona virus
- drug repurposing
- prevention
- senescence
- senolytic drug therapy
- viral replication
Prior evidence suggests that the choice of antihypertensive medication may influence functional status among older adults with hypertension, particularly in conjunction with exercise. In particular, angiotensin converting enzyme (ACE) inhibitors have shown potential to positively influence function. However, randomized, controlled trials are needed to confirm this hypothesis. This paper outlines an RCT designed to determine if choice of first-line antihypertensive medication influences functional and cardiovascular risk factor responses to exercise among older adults with hypertension. Two hundred and thirteen inactive, community-dwelling adults ≥60 years of age with hypertension and functional limitations will be recruited to engage in a 32-week intervention study. Participants will be randomized to one of three first-line antihypertensive agents: (1) the ACE inhibitor perindopril, (2) the AT1 receptor antagonist losartan, or (3) the thiazide diuretic hydrochlorothiazide (HCTZ). Six weeks after randomization, participants will begin a 20-week structured aerobic exercise intervention. Participants will perform two 45-min center-based sessions coupled with 60 min of home-based walking per week. The primary aim is to determine if perindopril improves self-paced gait speed when compared with losartan and HCTZ. The secondary aim is to determine the relative effect of perindopril on secondary outcomes such as: (a) exercise capacity, (b) body mass and composition, and (c) circulating indices of cardiovascular risk. This RCT is expected to identify differential effects of first-line antihypertensive medications when combined with physical exercise thus have potential implications for antihypertensive prescription guidelines for older adults. www.ClinicalTrials.gov, identifier: NCT03295734.
Keywords
- aging
- antihypertensive
- exercise
- functional status
- hypertension
{{medline-entry |title=Vascular age. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32013519 |abstract=Age can be evaluated according to many criteria. Of course the objective measure is the calendar age which may differ from the biological age. The biological age more or less correlates with the vascular age. The concept of vascular age is based on the statement that