Urinary C-type natriuretic peptide excretion: a potential novel biomarker for renal fibrosis during aging

Renal aging is characterized by structural changes in the kidney including fibrosis, which contributes to the increased risk of kidney and cardiac failure in the elderly. Studies involving healthy kidney donors demonstrated subclinical age-related nephropathy on renal biopsy that was not detected by standard diagnostic tests. Thus there is a high-priority need for novel noninvasive biomarkers to detect the presence of preclinical age-associated renal structural and functional changes. C-type natriuretic peptide (CNP) possesses renoprotective properties and is present in the kidney; however, its modulation during aging remains undefined. We assessed circulating and urinary CNP in a Fischer rat model of experimental aging and also determined renal structural and functional adaptations to the aging process. Histological and electron microscopic analysis demonstrated significant renal fibrosis, glomerular basement membrane thickening, and mesangial matrix expansion with aging. While plasma CNP levels progressively declined with aging, urinary CNP excretion increased, along with the ratio of urinary to plasma CNP, which preceded significant elevations in proteinuria and blood pressure. Also, CNP immunoreactivity was increased in the distal and proximal tubules in both the aging rat and aging human kidneys. Our findings provide evidence that urinary CNP and its ratio to plasma CNP may represent a novel biomarker for early age-mediated renal structural alterations, particularly fibrosis. Thus urinary CNP could potentially aid in identifying subjects with preclinical structural changes before the onset of symptoms and disease, allowing for the initiation of strategies designed to prevent the progression of chronic kidney disease particularly in the aging population.

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Structural and functional changes in the kidneys and their effect on cardiovascular risk in elderly patients

Актуальные проблемы медицины ◽

10.18413/2687-0940-2020-43-4-539-548 ◽

2020 ◽

Vol 43 (4) ◽

pp. 539-548

Author(s):

Natalya I. Golovina ◽

◽

Yury A. Lykov ◽

Keyword(s):

Chronic Kidney Disease ◽

Cardiovascular Risk ◽

Kidney Disease ◽

Elderly Patients ◽

Structural Changes ◽

Interstitial Fibrosis ◽

The Elderly ◽

Functional Changes ◽

Age Related ◽

Organ Systems

Like other organ systems, the kidneys also go through process of normal senescence, including both anatomical and physiological changes. Normal physiological aging is characterized by the expected age-related changes in the kidneys. With age, the kidneys are subject to structural changes, for example, there is a decrease in the number of functional glomeruli due to an increase in the prevalence of nephrosclerosis (atherosclerosis, glomerulosclerosis, atrophy of the tubules with interstitial fibrosis) and to some extent compensatory hypertrophy of the remaining nephrons. Older age is also associated with reduced cortical volume, increased medullary, and larger and more numerous renal cysts. Changes in normal aging are important in clinical practice. Against the background of suppression of reparative capabilities, the elderly are more prone to acute damage and chronic kidney disease, aggravation of the course of chronic kidney disease. The elderly have less renal functional reserve when they do actually develop chronic kidney disease and they are also at higher risk for acute kidney injury. Cardiovascular disease is a leading cause of death and a common comorbidity among patients with kidney disease. In this review, we have identified the most characteristic structural and functional changes in the kidneys in elderly patients and their impact on cardiovascular risk.

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Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽

10.1161/str.45.suppl_1.tp136 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

George Howard ◽

Mary Cushman ◽

Maciej Banach ◽

Brett M Kissela ◽

David C Goff ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Stroke Risk ◽

Multivariable Analysis ◽

The Elderly ◽

Stroke Risk Factors ◽

Age Related ◽

Increased Risk ◽

The Impact ◽

Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

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Constipation in patients with comorbidity

Лечащий врач ◽

10.51793/os.2021.24.12.010 ◽

2021 ◽

Author(s):

Е.А. Лялюкова ◽

Е.Н. Логинова

Keyword(s):

Gastrointestinal Tract ◽

Neurological Diseases ◽

The Elderly ◽

Lifestyle Changes ◽

Secretory Cells ◽

Endocrine Disorders ◽

Silver Age ◽

Functional Changes ◽

Slowing Down ◽

Age Related

Пациенты пожилого и старческого возраста в силу физиологических причин и коморбидной патологии имеют высокий риск развития запора. Причиной запора чаще всего являются алиментарные факторы и возраст-ассоциированные заболевания и повреждения толстой кишки (дивертикулярная болезнь, ишемия толстой кишки, ректоцеле, геморрой и другие); метаболические, эндокринные расстройства и неврологические заболевания. Возрастные анатомические, структурные и функциональные изменения пищеварительной системы вносят свой вклад в развитие запоров у пожилых. У пациентов «серебряного возраста» отмечено увеличение длины желудочно-кишечного тракта, прогрессирование атрофических, склеротических изменений слизистой и подслизистой оболочки, снижение количества секреторных клеток, замещение мышечных волокон соединительной тканью и др. Все это способствует замедлению транзита по желудочно-кишечному тракту и нарушению акта дефекации. Образ жизни пожилых людей также может способствовать развитию запора. Низкое содержание в рационе клетчатки, употребление преимущественно термически обработанной пищи, нарушение ритма питания (прием пищи 1-2 раза в день) являются одной из причин возникновения запоров у пожилых, чему способствуют трудности при жевании вследствие стоматологических проблем. Колоноскопия показана всем пациентам пожилого и старческого возраста с запором, а выявление «симптомов тревоги» необходимо проводить при каждом визите пациента. Вне зависимости от причины вторичного запора, все пациенты должны осуществлять ряд мер немедикаментозного характера, включающих изменение образа жизни, диету с включением достаточного количества клетчатки и потребление жидкости. Физические методы лечения могут включать лечебную гимнастику, массаж толстой кишки для стимуляции моторной активности кишечника в определенное время. При неэффективности немедикаментозных мероприятий рекомендуется использование осмотических слабительных, а также средств, увеличивающих объем каловых масс. Высокая эффективность и безопасность псиллиума позволяет рекомендовать его в лечении хронического запора у пожилых пациентов. Elderly and senile patients, due to physiological reasons and comorbid pathology, have a high risk of constipation. The causes of constipation are more often nutritional factors and age-associated diseases and damage to the colon (diverticular disease, colon ischemia, rectocele, hemorrhoids, and others); metabolic, endocrine disorders and neurological diseases. Age-related anatomical, structural and functional changes in the digestive system contribute to the development of constipation in the elderly. In patients of «silver age», there was an increase in the length of the gastrointestinal tract, the progression of atrophic, sclerotic changes in the mucous and submucosa, a decrease in the number of secretory cells, replacement of muscle fibers with connective tissue, etc. All this contributes to the slowing down of transit through the gastrointestinal tract and the violation of the act of defecation. Elderly lifestyles can also contribute to constipation. The low fiber content in the diet, the use of mainly thermally processed food, the violation of the rhythm of the diet (eating 1-2 times a day) are one of the causes of constipation in the elderly, which is facilitated by difficulty in chewing due to dental problems. Colonoscopy is ordered for all elderly and senile patients with constipation, and the identification of «anxiety symptoms» should be carried out at each patient visit. Regardless of the cause of secondary constipation, all patients should take a number of non-pharmacological measures, including lifestyle changes, a diet with adequate fiber, and fluid intake. Physical therapies may include medical gymnastics, colon massage to stimulate bowel movement at specific times. If non-drug measures are ineffective, it is recommended to use osmotic laxatives, as well as agents that increase the volume of feces. Psyllium supplementation is recommended for treatment of chronic constipation in elderly patients due to its high efficacy and safety.

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Abstract P329: White Matter Score Does Not Predict Post-tPA Hemorrhage in Elderly Patients Evaluated Acutely via Telestroke

Stroke ◽

10.1161/str.52.suppl_1.p329 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Muhammad Bilal Tariq ◽

Shekhar Khanpara ◽

Eliana Bonfante Mejia ◽

Liang Zhu ◽

Christy T Ankrom ◽

...

Keyword(s):

White Matter ◽

Elderly Patients ◽

The Elderly ◽

Periventricular White Matter ◽

Severe Stroke ◽

Age Related ◽

Increased Risk ◽

Symptomatic Intracranial Hemorrhage ◽

Relationship Of ◽

Patient Presentation

Background: While tPA may be safe in the elderly, increasing age appears to augment risk of post-tPA symptomatic intracranial hemorrhage (sICH). Age-related white matter changes (ARWMC) are associated with increased sICH. Patients evaluated for acute ischemic stroke (AIS) via telestroke (TS) may not have access to MRI to allow incorporation of microbleeds in tPA decisions. We assessed if increased CT-based ARWMC was associated with increased sICH in elderly patients. Methods: Patients 80 years and older who received tPA for AIS at spoke hospitals were selected from our TS network registry from 9/2015 to 12/2018. TS spoke CT scans from patient presentation were reviewed by three of the authors for periventricular white matter (PWMC) and deep white matter (DWMC) changes. Total ARWMC score, based on the Fazekas score, was collected. Total ARWMC score was either mild (0-2), moderate (3-4), or severe (5-6). PWMC and DWMC were either mild (0-1) or moderate-severe (2-3). Logistic regression adjusted for age, sex, race, ethnicity, NIHSS and premorbid mRS was used to analyze relationship of ARWMC scores with sICH and patient-outcomes. Results: Of 241 patients, median age overall was 86 years (IQR 83-90), and 66% were female. The overall median ARWMC score was 3 (IQR 2-5). Regression analysis showed that more severe ARWMC scores did not lead to higher frequency of post-tPA ICH (moderate OR 0.57, CI 0.19-1.71; severe OR 1.32, CI 0.48-3.65) including sICH (moderate OR 0.78, CI 0.21-2.94; severe OR 2.09, CI 0.62-7.02). Similarly, severe PWMC and DWMC were not associated with increased risk of post-tPA ICH (PWMC OR 1.31, CI 0.51-3.38; DWMC OR 1.25, CI 0.52-3.01), including sICH (PWMC OR 1.61, CI 0.51-5.08; DWMC OR 1.81, CI 0.65-5.01). In our cohort, older patients had no difference in hemorrhage (ICH OR 0.93 CI 0.85-1.00: sICH OR 0.95 CI 0.86-1.04), and patients with less severe stroke were more likely to have hemorrhage (ICH OR 1.06 CI 1.02-1.10; sICH OR 1.08 CI 1.03-1.13). IRR among the CT scan readers was moderate (k=0.504). Conclusions: ARWMC scores were not associated with post-tPA ICH in the elderly. Our analysis lends support for the use of tPA despite severity of white matter disease. ARWMC should not be used to assist in tPA decision-making in elderly patients via telestroke.

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Regenerative Medicine Approaches for Age-Related Muscle Loss and Sarcopenia: A Mini-Review

Gerontology ◽

10.1159/000479278 ◽

2017 ◽

Vol 63 (6) ◽

pp. 580-589 ◽

Cited By ~ 16

Author(s):

Juan Diego Naranjo ◽

Jenna L. Dziki ◽

Stephen F. Badylak

Keyword(s):

Regenerative Medicine ◽

Treatment Options ◽

The Elderly ◽

Signaling Molecules ◽

Current Treatment ◽

Muscle Physiology ◽

Age Related ◽

Increased Risk ◽

And Function ◽

Age Related Changes

Sarcopenia is a complex and multifactorial disease that includes a decrease in the number, structure and physiology of muscle fibers, and age-related muscle mass loss, and is associated with loss of strength, increased frailty, and increased risk for fractures and falls. Treatment options are suboptimal and consist of exercise and nutrition as the cornerstone of therapy. Current treatment principles involve identification and modification of risk factors to prevent the disease, but these efforts are of limited value to the elderly individuals currently affected by sarcopenia. The development of new and effective therapies for sarcopenia is challenging. Potential therapies can target one or more of the proposed multiple etiologies such as the loss of regenerative capacity of muscle, age-related changes in the expression of signaling molecules such as growth hormone, IGF-1, myostatin, and other endocrine signaling molecules, and age-related changes in muscle physiology like denervation and mitochondrial dysfunction. The present paper reviews regenerative medicine strategies that seek to restore adequate skeletal muscle structure and function including exogenous delivery of cells and pharmacological therapies to induce myogenesis or reverse the physiologic changes that result in the disease. Approaches that modify the microenvironment to provide an environment conducive to reversal and mitigation of the disease represent a potential regenerative medicine approach that is discussed herein.

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Low vitamin D status is associated with hearing loss in the elderly: a cross-sectional study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa310 ◽

2020 ◽

Author(s):

Betsy Szeto ◽

Chris Valentini ◽

Anil K Lalwani

Keyword(s):

Vitamin D ◽

Hearing Loss ◽

Low Frequency ◽

The Elderly ◽

Vitamin D Status ◽

Total Calcium ◽

Mineral Density ◽

Cross Sectional ◽

Age Related ◽

Increased Risk

ABSTRACT Background The elderly are at increased risk of both hearing loss (HL) and osteoporosis. Bone mineral density (BMD) has been putatively linked to HL. However, the roles of serum calcium concentrations and vitamin D status have yet to be elucidated. Objectives The purpose of this study was to examine the relation between vitamin D status, parathyroid hormone (PTH), total calcium, BMD, and HL in a nationally representative sample of elderly adults. Methods Using the NHANES (2005–2010), audiometry and BMD data of 1123 participants aged ≥70 y were analyzed in a cross-sectional manner. HL was defined as pure tone averages >25 dB HL at 500, 1000, and 2000 Hz (low frequency); 500, 1000, 2000, and 4000 Hz (speech frequency); and 3000, 4000, 6000, and 8000 Hz (high frequency) in either ear. Multivariable logistic regression was used to examine the relation between HL and total 25-hydroxyvitamin D [25(OH)D], PTH, total calcium, and BMD, adjusting for covariates. Results In multivariable analyses, total 25(OH)D < 20 ng/mL was found to be associated with greater odds of low-frequency HL (OR: 2.02; 95% CI: 1.28, 3.19) and speech-frequency HL (OR: 1.96; 95% CI: 1.12, 3.44). A 1-unit decrease in femoral neck BMD (OR: 4.55; 95% CI: 1.28, 16.67) and a 1-unit decrease in total spine BMD (OR: 6.25; 95% CI: 1.33, 33.33) were found to be associated with greater odds of low-frequency HL. Serum PTH and total calcium were not found to be associated with HL. Conclusions In the elderly, low vitamin D status was associated with low-frequency and speech-frequency HL. Low vitamin D status may be a potential risk factor for age-related HL.

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Pairing Cholinergic Enhancement with Perceptual Training Promotes Recovery of Age-Related Changes in Rat Primary Auditory Cortex

Neural Plasticity ◽

10.1155/2016/1801979 ◽

2016 ◽

Vol 2016 ◽

pp. 1-18 ◽

Cited By ~ 13

Author(s):

Patrice Voss ◽

Maryse Thomas ◽

You Chien Chou ◽

José Miguel Cisneros-Franco ◽

Lydia Ouellet ◽

...

Keyword(s):

Auditory Cortex ◽

Structural Changes ◽

Primary Auditory Cortex ◽

Auditory Training ◽

Tone Frequency ◽

Perceptual Training ◽

Adult Rats ◽

Functional Changes ◽

Age Related ◽

Old Rats

We used the rat primary auditory cortex (A1) as a model to probe the effects of cholinergic enhancement on perceptual learning and auditory processing mechanisms in both young and old animals. Rats learned to perform a two-tone frequency discrimination task over the course of two weeks, combined with either the administration of a cholinesterase inhibitor or saline. We found that while both age groups learned the task more quickly through cholinergic enhancement, the young did so by improving target detection, whereas the old did so by inhibiting erroneous responses to nontarget stimuli. We also found that cholinergic enhancement led to marked functional and structural changes within A1 in both young and old rats. Importantly, we found that several functional changes observed in the old rats, particularly those relating to the processing and inhibition of nontargets, produced cortical processing features that resembled those of young untrained rats more so than those of older adult rats. Overall, these findings demonstrate that combining auditory training with neuromodulation of the cholinergic system can restore many of the auditory cortical functional deficits observed as a result of normal aging and add to the growing body of evidence demonstrating that many age-related perceptual and neuroplastic changes are reversible.

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Abstract 12954: Impairment of the Compensatory Natriuretic Peptide Response to Myocardial Infarction in the Aged is Associated With Adverse Cardiorenal Repair and Heart Failure

Circulation ◽

10.1161/circ.130.suppl_2.12954 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

S. J Sangaralingham ◽

Tomoko Ichiki ◽

Gerald E Harders ◽

Horng H Chen ◽

John C Burnett

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Natriuretic Peptide ◽

The Elderly ◽

Significant Loss ◽

Coronary Artery Ligation ◽

Artery Ligation ◽

Aged Rat ◽

Clinical Model ◽

Increased Risk

Introduction: The incidence of post-myocardial infarction (MI) heart failure (HF) is increasing in the elderly. Studies have demonstrated that B-type natriuretic peptide (BNP) mediates critical cardiorenal compensatory and protective actions through guanylyl cyclase receptor A and cGMP activation. Such actions include natriuresis, diuresis and suppression of adverse cardiorenal remodelling. Hypothesis: While the mechanism of this increased risk may be multifactorial, we hypothesized that an impairment of the compensatory protective BNP/cGMP axis in both the aged kidney and heart contributes to post-MI HF. Methods: 20 month old Fischer rats were randomized into two groups: Sham-operated (S) and MI(produced by left coronary artery ligation). Cardiorenal structure and function were assessed at 4 weeks and included mean arterial pressure(MAP), LV EF, LV chamber dimension, proteinuria, sodium (Na) excretion and fibrosis by picrosirius red staining. Plasma BNP and cGMP levels were assessed by RIA. Data presented as mean±SE,*P<0.05. Results: LV EF (S:78±2, MI:46±3 %*) was significantly reduced in aged MI rats, despite no difference in LV fibrosis in the remote region and no change in MAP compared to aged sham rats. Post-MI HF was evident and characterized by a significant reduction in Na excretion (S:0.20±0.03, MI:0.13±0.01 mEq/day*) as well as significant increases in LV dilatation (S:7.2±0.1, MI:8.3±0.2 mm*) and cardiac hypertrophy (S:2.78±0.06, MI:3.25±0.16 mg/g*) in aged MI rats. Notably, plasma BNP (S:9±1, MI:11±2 pg/ml) failed to increase and plasma cGMP (S:44±6, MI:27±3 mm*) was significantly reduced in the MI group. Importantly, MI in the aged rat resulted in a significant loss in total renal mass (S:2739±83, MI:2351±68 mg*), consistent with renal atrophy, while no changes in proteinuria or renal fibrosis were observed. Conclusions: Post-MI dysfunction of the protective BNP/cGMP axis in the aged rat was associated with various cardiorenal abnormalities including renal atrophy, which may contribute to the pathophysiology of HF. This pre-clinical model provides new insights into post-MI HF and may be used to examine therapeutic strategies using natriuretic peptides to protect the heart and kidney in the elderly post-MI population.

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Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19

Innovation in Aging ◽

10.1093/geroni/igab046.1283 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 332-332

Author(s):

Ranran Zhai ◽

Timothy Pyrkov ◽

Anastasia Shindyapina ◽

Marco Mariotti ◽

Peter Fedichev ◽

...

Keyword(s):

Immune Cell ◽

The Elderly ◽

Significant Negative Correlation ◽

Epidemiological Studies ◽

Notch Signaling Pathway ◽

Biological Age ◽

Risk Of Death ◽

Age Related ◽

Increased Risk ◽

Clock Models

Abstract Epidemiological studies revealed that the elderly and those with comorbidities are most susceptible to COVID-19. To understand how genetics affects the risk of COVID-19, we conducted a multi-instrument Mendelian Randomization (MR) analysis and found that the genetic variation that supports a longer life is significantly associated with the lower risk of COVID-19 infection, as well as being hospitalized after infected. The odds ratio is 0.31 (P = 9.7e-6) and 0.46 (P = 3.3e-4), respectively, per additional 10 years of life. We further applied aging clock models and detected an association between biological age acceleration and future incidence and severity of COVID-19 infection for all subjects and individuals free of chronic disease. Biological age acceleration was also significantly associated with the risk of death in COVID-19 patients. A bivariate genomic scan for age-related COVID-19 infection identified a key contribution of the Notch signaling pathway and immune system. Finally, we performed MR using 389 immune cell traits as exposure and observed a significant negative correlation between their effect on lifespan and COVID-19 risk, especially for B cell-related traits. More specifically, we discovered the lower CD19 level on B cells indicates an increased risk of COVID-19 and potentially decreases the lifespan expectancy, which is further validated in clinical data from COVID-19 patients. Our analysis suggests that the factors that accelerate aging and limit lifespan cause an increased COVID-19 risk. Thus, the interventions target these factors (e.g., reduce biological age), after further validation, may have the opportunity to reduce the risk of COVID-19.

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COMPARISON OF PROPENSITY TO FALLS IN MALE AND FEMALE ELDERLY AND ITS CORRELATION BETWEEN THE BALANCE AND COGNITION LEVEL

Manual Therapy Posturology & Rehabilitation Journal ◽

10.17784/mtprehabjournal.2018.16.561 ◽

2020 ◽

pp. 1-6

Author(s):

Élcio Alves Guimarães ◽

Kennedy Rodrigues Lima ◽

Flávia Fernandes Oliveira ◽

Renato Mota da Silva ◽

Lucas Resende Sousa ◽

...

Keyword(s):

Mental State ◽

Mini Mental State Examination ◽

The Elderly ◽

The Other ◽

Timed Up And Go ◽

Functional Changes ◽

Functional Reach ◽

Increased Risk ◽

Risk Of Fall ◽

State Examination

Background: Aging is a dynamic, progressive and physiological process, accompanied by morphological and functional changes, as well as biochemical and psychological changes, resulting in a decrease in the functional reserve of organs and system. With aging, functional losses occur, so the elderly have a greater predisposition to falls. Objective: To compare the propensity to falls between elderly men and women correlating with the level of cognition and balance. Methods: The sample consisted of 60 elderly people, of which 30 were male and 30 were female both aged 65 to 80 years. The propensity to falls was assessed using the “Timed Up and Go” and “Functional Reach” tests, and the state of cognition was assessed by the test “Mini-Mental State Examination”. Results: The results obtained with Time Up and Go, Functional Reach and the Mini-Mental State Examination, indicated that, as the values of one of the variables increase, the values of the other variable increase too; as the values of one of the variables decrease, the values of the other variable increase too. Conclusions: It can be concluded that there was no increased risk of fall when compared the genders; but the female presented altered cognitive deficit.

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