Testosterone supplementation's effects on age-related bladder remodeling – experimental study in rats

Abstract

Objective: This study was designed to evaluate the effect of testosterone replacement on the fibrotic process of the detrusor bladder muscle during the normal aging process.

Methods: 15 Wistar senile rats, aged between 18 and 20 months were divided into two groups: testosterone group – 11 animals submitted to the administration of testosterone undecanoate (50?mg/kg intramuscular), once per month; and, Control group – four animals underwent a sham procedure. At the end of eight weeks, animals from both groups were sacrificed; bladders were removed and subsequently stereologically evaluated to determine the volumetric density of collagen fibers. The success of testosterone administration was confirmed by the measurement of serum testosterone at the beginning and end of the experiment.

Results: In the replacement group, testosterone average was 3.2?ng/ml, whereas in the control group, the mean testosterone at the end of the experiment was 0.64?ng/ml (p?<?0.05). Analysis of stereological collagenous fiber showed higher density in the control group compared to the testosterone group I (56% versus 37.02%, respectively). The difference of volume concentration of collagen between both groups was statistically significant (p?<?0.000).

Conclusion: Bladder wall fibrosis was reduced in senile rats subjected to testosterone replacement.     

The effects of orchidectomy and supraphysiological testosterone administration on trabecular bone structure and gene expression in rats

Abstract

Objective: This study aimed to determine the effects of orchidectomy and supraphysiological testosterone replacement on trabecular structure and gene expression in the bone.

Methods: Twenty-four 3-month old male rats were randomized into sham (SH), orchidectomized (ORX) and testosterone-treated (TE) groups. Orchidectomy was performed on the ORX and TE group. Weekly testosterone enanthate intramuscular injection at 7?mg/kg body weight was administered to the TE group for 8 weeks while the other groups received peanut oil as vehicle. Blood was collected before and after treatment for serum testosterone analysis. The femora and tibiae were harvested after the treatment period for trabecular structure and gene expression analysis.

Results: The trabecular bone volume decreased significantly and the porosity increased significantly in the ORX group compared to the SH group (p?<?0.05). Testosterone treatment prevented all these changes (p?<?0.05). The expression of osteogenic genes decreased significantly in the ORX group compared to the SH group (p?<?0.05). Testosterone treatment decreased the expressions of RANKL and OPG genes significantly (p?<?0.05).

Conclusion: Orchidectomy-induced degeneration in trabecular structure is caused by a decrease in the expressions of osteogenic genes. Supraphysiological testosterone replacement is able to prevent these degenerative changes in the bone despite the modest changes in gene expression.     

Association between testosterone levels and the metabolic syndrome in adult men

Abstract

Objective: To evaluate the relationship between testosterone levels and the metabolic syndrome (MS) in men older than 45 years.

Methods: Six hundred and sixty men (45–70 years) selected from 2906 participants of a population screening for prostate cancer were included in this study. Testosterone and the components of MS were assessed in all men. MS was diagnosed according to NCEP-ATP III criteria. Triglycerides (TG)/HDL-cholesterol (chol) index was calculated.

Results: The presence of MS was inversely associated with testosterone (χ², p?<?0.001), independently of age (OR 0.802, CI 95%: 0.724–0.887, p?<?0.0001). Hypertension was the most frequent abnormality observed followed by elevated TG and waist circumference (WC). Testosterone correlated positively with HDL-chol (r: 0.14, p?<?0.0001) and negatively with body mass index (BMI)(r: ?0.29, p?<?0.0001), WC (r: ?0.26, p?<?0.0001), TG (r: ?0.20, p?<?0.0001), TG/HDL-chol (r: ?0.20, p?<?0.0001), glucose (r: ?0.11, p?=?0.005) and MS score (r: ?0.23, p?<?0.0001).

Conclusions: Our results show that in men older than 45 years, as long as testosterone levels decline, the prevalence of MS increases, independently of age. The correlations found between testosterone and four of the five components of MS, as well as with BMI and TG/HDL-chol ratio, a surrogate marker of insulin resistance, suggest considering male hypogonadism as a determinant of developmental abnormalities typical of MS.     

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study

Purpose.?We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH).

Methods.?Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250?mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment.

Results.?Forty-six patients (ART group, n?=?23; control, n?=?23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7?±?8.7 vs. 12.5?±?9.5; p?<?0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p?<?0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p?<?0.05), whereas no significant changes were seen in the controls.

Conclusion.?ART improved LUTS in hypogonadal men with mild BPH.     

Serum levels of inhibin B in men of different age groups

The decline of testosterone levels in aging men is well documented. However, it is unclear to what extent the Sertoli cell marker inhibin B changes during aging. Herein we report on the determination of serum levels of inhibin B, follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in 906 patients from 16 to 89 years of age, presenting to our department for different complaints. There was a weak but significant correlation of the levels of inhibin B with age (r = 0.064, p < 0.05). A significant negative correlation of FSH and inhibin B was documented in all age groups (r = -0.423, p < 0.01). Also, the LH levels increased significantly with low inhibin B levels (r = -0.289, p < 0.01). Testosterone levels showed no significant correlation with inhibin B. We conclude from our study that Sertoli cell function as documented by serum levels of inhibin B is stable throughout life. In addition, the ongoing correlation of FSH and inhibin levels also indicates no significant decline of Sertoli cell function in the aging male.     

Effects of testosterone treatment on body composition in males with testosterone deficiency syndrome

Abstract

Objective: We evaluated the safety of testosterone treatment and its efficacy on body composition in males with testosterone deficiency syndrome (TDS) over 24 months.

Methods: 50 males aged 50–65 years with TDS (Aging Males Symptoms Scale [AMS]?>?26 and calculated free testosterone [cFT] 250?pmol/l) were administered 50?mg testosterone gel daily for one year. During the second year, patients received 1000?mg of testosterone undecanoate every 2–3 months. Outcome measures were clinical chemistry values and total testosterone; sex hormone-binding globulin and cFT, changes in AMS and International Prostate Symptom Score; and changes in body composition measured by dual-energy-x-ray absorptiometry.

Results: There were no clinically significant changes in clinical chemistry safety parameters. There were significant improvements in both total and cFT and in AMS scores after three months (p?<?0.001). Lean mass increased 2.35% at 12 months and 4.5% at 24 months, but proportionally more muscle mass was gained in arms and legs than in the trunk. Fat mass decreased 4.2% at 12 months and 9.1% at 24 months.

Conclusions: Testosterone treatment in males with TDS leads to body changes affecting lean and fat mass with significant improvement in AMS scores, and has an excellent safety profile.     

Effect of testosterone therapy on lumbar spine and hip mineral density in elderly men

Objective.?The aim of the present study was to analyse the effect of testosterone therapy on bone mineral density in healthy elderly men who had low levels of total testosterone.

Design.?Randomized, double-blind, placebo-controlled study.

Participants.?Forty-eight men over 60 years old with decreased testosterone levels (≤320 ng/dL) comprised the study. Twenty-five out of 48 received intramuscular injections of testosterone enanthate every three weeks during 12 months; the remaining 23 participants formed the control group. All participants had measurements of bone mineral density (BMD) in both lumbar spine and hip before and at the end of the study as well as testosterone and 17-β estradiol levels.

Results:?Testosterone treated group exhibited a significant (p < 0.05) increment (from 1.198 ± 0.153 to 1.240 ± 0.141 g/cm²) in lumbar BMD in parallel with a significant (p < 0.001) increment (from 301 ± 32 to 471 ± 107 ng/dL) in testosterone concentrations, whereas no significant change occurred in femoral neck BMD.

Conclusions.?Testosterone therapy elicited a positive effect only in lumbar BMD in elderly men with diminished testosterone serum levels.     

Testosterone is associated with age-related changes in bone health status,muscle strength and body composition in men

Objective: Variations in testosterone levels are associated with several outcomes of aging. The present study aimed to examine the relationship between age-related decline of testosterone levels and changes in bone health status, handgrip strength, body fat percentage and fat-free mass. Materials and methods: A total of 335 Malaysian Chinese and Malay men aged 40 years and above were recruited for this study. Their body compositions, calcaneal speed of sound and handgrip strength were measured and their blood was collected. Linear regression analysis was done to examine the relationship among age, testosterone levels and outcomes of aging. Results: The results indicated significant changes in all testosterone measurements, sex hormone binding globulin level, calcaneal speed of sound, handgrip strength, body fat percentage and fat-free mass with age (p < 0.05). Age-dependent decline in bioavailable and free testosterone levels were significantly associated with reduction in calcaneal speed of sound, fat-free mass and handgrip strength (p < 0.05). Age-dependent decline in the total testosterone level was significantly associated with an increase in body fat percentage among the elderly men (p < 0.05). Conclusion: Testosterone levels are associated with changes in outcome of aging such as bone health status, muscle strength and body composition, and the relationships are age-dependent.     

Change in testosterone concentrations over time is a better predictor than the actual concentrations for symptoms of late onset hypogonadism

Abstract

Background. Symptoms of late-onset hypogonadism (LOH) and concentrations of testosterone (T) and bioavailable testosterone (BT) were studied in relation to the data from the same men 5 years earlier.

Methods.?In 2008, 282 men, aged 60–82 years, answered a questionnaire regarding demographic data, medical history, different symptoms of LOH and the 10 questions from the ‘Androgen Decline in Aging Males (ADAM)-questionnaire’. Blood samples were analysed for concentrations of T and calculations were made for BT.

Results.?A total of 87.2% of the questionnaires were returned and analysed, and 75.2% of the responders gave blood samples. The oldest third of the men were most affected by LOH symptoms (p?<?0.05). Both T and BT concentrations decreased during the 5 years (p?<?0.05) but only the symptom ‘less strong erections’ changed significantly (p?<?0.05). Men reporting one of the four specific symptoms from the ‘ADAM-questionnaire’ for the first time in 2008 had a higher loss of T and BT than men who had unchanged or fewer symptoms than that reported in 2003.

Conclusions.?The magnitude of the decrease in concentrations is a better predictor of LOH than are the actual concentrations of T and BT. A combination of symptoms predicts LOH better than any single symptom.     

Testosterone deficiency in male heart failure patients and its effect on endothelial progenitor cells

Background: Endothelial progenitor cells (EPCs) are thought to contribute to reendothelialization and neoangiogenesis. Since it is known that EPCs express a testosterone receptor, we wanted to assess the prevalence of testosterone deficiency in patients with CHF and its impact on circulating EPCs. Methods: 137 male patients with chronic heart failure (CHF) were included (age 61?±?13 years; BMI 29?±?5?kg/m²; New York Heart Association classification (NYHA) I: n = 47, NYHA II: n = 51, NYHA III: n = 39). Numbers of different populations of circulating EPCs were quantified using flow cytometry. Levels of free testosterone and EPC-regulating cytokines were determined using ELISA. Results: The prevalence of testosterone deficiency in our University CHF clinic was 39%. However, there was no difference between patients with and without testosterone deficiency regarding their levels of EPCs. Testosterone levels were inversely correlated with age (R² = ?0.32, p = 0.001) and NYHA status (R² = 0.28, p = 0.001) and correlated with cardiorespiratory capacity (R² = 0.26, p = 0.03). Conclusion: Testosterone deficiency is frequent in male patients with CHF but does not appear to impact the regenerative EPCs.     

A randomized,double-blind,placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up

Introduction: The clinical significance of low to low-normal testosterone (T) levels in men remains debated. Aim: To analyze the effects of raising serum T on lean body mass (LBM), fat mass (FM), total body mass, and health-related quality-of-life (HRQoL). Methods: Randomized, double-blind, placebo-controlled study. Men, aged 50–80 years, with serum total T<15 nmol/L and bioavailable T < 6.68 nmol/L, and a Aging Males’ Symptoms (AMS) total score >36, received 6 months treatment with transdermal 1% T gel (5–7.5?mg/day; n =183) or placebo gel (n =179), followed by 12 months open-label with T in all. Results: After 6 months, LBM increased in T- treated patients by 1.28?±?0.15?kg (mean ± SE) and FM decreased by 1.16?±?0.16?kg, with minor changes with placebo (LBM +0.02?±?0.10?kg and FM ?0.14?±?0.12?kg; all p < 0.001, T group vs. placebo). Changes were largely similar across subgroups of age, baseline total testosterone, and baseline BMI. Total HRQoL improved compared with placebo (p < 0.05, T group vs. placebo). Conclusions: Six months 1% T gel improved body composition and HRQoL in symptomatic men with low to low-normal T, with further improvements over the following 12 months.     

Association between serum levels of testosterone and biomarkers of subclinical atherosclerosis

Objective: To investigate the association between serum levels of testosterone and biomarkers of subclinical atherosclerosis based on data from 119 middle-aged men of the general population.

Methods: Testosterone, Apolipoprotein A-1 (ApoA-1), Apolipoprotein B (ApoB), Apolipoprotein B-to-Apolipoprotein A-1 ratio (ApoB-to-ApoA-1), high-sensitive C-reactive protein (hsCRP), and fibrinogen levels were measured. Data were also gathered based on age, BMI, waist circumference, smoking, alcohol consumption, and family history of cardiovascular diseases. Men were classified into two groups based on testosterone levels: hypogonadal (testosterone ≤12?nmol/L) and eugonadal men (testosterone >12?nmol/L).

Results: When compared to eugonadal, the hypogonadal men were significantly older (56?years vs. 55?years, p?=?.03), had greater BMI (28?kg/cm² vs. 26?kg/cm², p?=?.01), and higher waist circumference (104?cm vs. 100?cm, p?=?.01). Moreover, ApoB, ApoB-to-ApoA-1 ratio, and hsCRP were significantly higher in hypogonadal men compared to eugonadal men (1.1?g/L vs. 1.0?g/L, p?=?.03), (0.8 vs. 0.7, p?=?.03), (3.3?mg/L vs. 2.0?mg/L, p?=?.01), respectively. On the other hand, ApoA-1 and fibrinogen levels did not differ significantly between groups (p?>?.05). In an adjusted multivariate regression analysis model, only ApoB showed a significant negative association with testosterone levels (β?=??0.01; 95% CI?=??0.02, ?1.50; p?=?.04).

Conclusion: Testosterone levels showed an inverse relation to ApoB, a biomarker implicated in subclinical atherosclerosis. These findings support the hypothesis that low testosterone levels play a role in atherosclerosis.     

The aging male in African ethnic cultures

Objective.?To test the relationship between gonadal status and objective measures and determinants of physical performance in older men and their determinants.

Methods.?The study included 455?≥?65 year older men of InCHIANTI study, Italy, with complete data on testosterone levels, hand grip strength, cross-sectional muscle area (CSMA), short physical performance battery (SPPB). Linear models were used to test the relationship between gonadal status and determinants of physical performance.

Results.?Three different groups of older men were created: (1) severely hypogonadal (N?=?23), total testosterone levels ≤230?ng /dl; (2) moderately hypogonadal (N?=?88), total testosterone >230 and?N?=?344), testosterone levels ≥350?ng/dl. With increased severity of hypogonadal status, participants were significantly older while their BMI was substantially similar. In the age and BMI adjusted analysis, there was a significant difference in haemoglobin levels, hand grip strength and SPPB score (p for trend?p for trend?=?0.004) and haemoglobin (p for trend?Conclusions.?In older men, gonadal status is independently associated with some determinants (haemoglobin and muscle strength) of physical performance.     

The relationship between serum total testosterone and free testosterone levels with serum hemoglobin and hematocrit levels: a study in 1221 men

Objective: To investigate the relationship between serum total testosterone (TT) and free testosterone (FT) levels in men with anemia.

Methods: We reviewed the records of 1221 subjects between March 2009 and December 2014. All the subjects’ blood samples were drawn for TT and FT assays. Their serum hemoglobin (Hb) and serum hematocrit (Hct) levels were measured. The primary objective of our study was to investigate the association between TT and FT levels with Hb and Hct levels.

Results: The mean age was 59.82?±?12.71 years. The mean TT and FT levels were 4.54?±?2.02?ng/mL and 10.63?±?3.69?pg/mL, respectively. The mean Hb and Hct levels were 14.72?±?1.34?g/dL and 43.11?±?3.75%, respectively. Subjects with low TT (<2.35?ng/mL) had low Hb and Hct levels (p?p?Conclusions: Subjects with low TT and FT levels had low Hb and Hct levels. This suggests that TT and FT play a significant role in erythropoiesis. Testosterone replacement therapy may be effective in men with hypogonadism to reduce the incidence of anemia.     

Endogenous testosterone and brachial artery endothelial function in middle-aged men with symptoms of late-onset hypogonadism

In aging men, serum endogenous testosterone is inversely associated with common carotid intima-media thickness (IMT) and directly with beneficial plasma lipid levels; however, the relationship to endothelial function is poorly characterized. We examined the association between serum testosterone and endothelium-dependent brachial artery flow-mediated dilatation (FMD) in middle-aged to elderly men. A group of 83 men aged 40–69 years (mean 55.9?±?7.5 [SD]) with andropausal symptoms were studied. We measured their serum lipids, testosterone, luteinizing hormone, mean carotid IMT and brachial artery FMD by high resolution B-mode ultrasound. Brachial FMD correlated inversely with vessel diameter (r?=??0.38, p?=?0.0004), alcohol consumption (r?=??0.22, p?=?0.047) and serum testosterone (r?=??0.27, p?=?0.01), but not with luteinizing hormone. In multivariate analysis, FMD was explained by testosterone (β?=??0.17, p?=?0.0226), high density lipoprotein cholesterol (β?=?4.17, p?=?0.0312) and vessel diameter (β?=??4.37, p?<?0.0001) when adjusted for age, body mass index, triglycerides, blood pressure, carotid IMT, smoking, alcohol consumption, cardiovascular diseases and use of lipid lowering medication (HMG-CoA reductase inhibitors). In middle-aged to elderly men, there is an inverse correlation between serum testosterone and brachial FMD. These data suggest that testosterone may have an adverse effect on systemic endothelial function.     

The age-testosterone relationship in black,white, and Mexican-American men,and reasons for ethnic differences

Recent studies give contradictory findings regarding testosterone levels in white, black, and Hispanic men. Here, I present a cross-sectional reanalysis of serum testosterone and sex hormone-binding globulin (SHBG) in 1637 males, aged 12–90, who participated in the morning examination of the Third National Health and Nutrition Examination Survey (NHANES III) during the year 1988–1991. Testosterone and SHBG in males are described precisely over the age range 12 to 90 years. Testosterone and SHBG are not notably different in white and Mexican-American (MA) males. In the age range 20–69 years, black men average 0.39 ng/ml higher testosterone than white and MA men (p < 0.001). The higher testosterone in black men is partly explained by low marriage rate and low adiposity.     

Testosterone is not associated with mortality in older African-American males

Introduction.?Although testosterone and its association with disease progression and mortality is a widely studied topic, no studies have evaluated mortality risks related to testosterone levels in an older African-American population. The mechanisms for known racial differences in mortality risk for certain cancers and cardiovascular risk factors are largely unknown. Elucidating a mortality risk associated with testosterone levels may give insight into the elevated risk for certain diseases in African-Americans.

Methods and results.?Study data were derived from a cohort 622 African-Americans (age 80.05?±?6.4, range 68–102) from Saint Louis, Missouri that includes 190 males (age 79.38?±?6.2, range 70–102). The eligible sample for this report includes 56 of the 190 males (age 78.89?±?6.9, range 70–102) who donated blood at baseline in 1992–1994 and subsequently tested for total testosterone and bioavailable testosterone. Covariates for adjusted analyses were lower body functional limitations, physician visits and comorbidities, also collected at baseline. Males' mean bioavailable testosterone levels (ng/dl) were 33.33?±?24.4 (n above 70?ng/dl?=?5) and mean total testosterone levels (ng/dl) were 246.63?±?118.7 (n above 300?ng/dl?=?20). Vital status was determined through 2002; 41 males (73%) were deceased and 15 were alive. Mortality did not differ among males with testosterone levels?<300 versus 300+ (p?=?0.42) or with bioavailable testosterone levels?<70 versus > 70 (p?=?0.34). Total testosterone levels did not predict mortality when adjusted for age (Adjusted Hazard Ratio [AHR]?=?0.998; 95% confidence interval [CI] 0.995–1.001; p?=?0.28) or adjusted for age and other covariates (AHR?=?0.099; 95% CI 0.996, 1.002; p?=?0.35). Bioavailable testosterone levels did not predict mortality when adjusted for age (AHR?=?0.992; 95% CI .977–1.007; p?=?0.30) or when adjusted for age and other covariates (AHR 0.991; 95% CI .976–1.006; p?=?0.261).

Conclusion.?In older African-American males, total and bioavailable testosterone levels, with and without adjustment for covariates, are not independently associated with mortality risk.     

Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis

Background Because of the great controversy over the role of androgens in the pathogenesis of atherosclerosis, we investigated the relationship between serum sex hormone levels and angiographically confirmed coronary artery disease in men.

Material and methods We investigated 86 men aged 40–60 years, 56 with coronary artery disease and 30 healthy men, matched by age, as a control group. Body mass index and waist to hip ratio were calculated and total body fat mass and percentage of abdominal deposit were investigated by dual-energy X-ray absorptiometry (Dpx (?+?) Lunar, USA). The serum levels of sex hormones and insulin were measured using commercial radioimmunoassay and IRMA (by SHBG) kits (DPC, USA). The serum levels of lipids and glucose were assessed by means of enzymatic methods.

Results Men with coronary artery disease had lower total testosterone levels (17.01?±?6.42 vs. 19.37?±?6.58?nmol/l; p?<?0.05), testosterone/estradiol ratio (228.5?±?88.5 vs. 289.8?±?120.1; p?<?0.05) and free androgen index (FAI) (59.49?±?14.79 vs. 83.03?±?25.81; p?<?0.0001), and higher levels of estrone (49.5?±?27.7 vs. 36.6?±?12.7?pg/ml) than men in the control group. Moreover, men with coronary artery disease were more insulin-resistant than controls and had an atherogenic lipid profile. There was an inverse correlation (p?<?0.05) between testosterone level and serum level of glucose (r?=??0.29), triglycerides (r?=??0.37), body mass index (r?=??0.55), waist (r?=??0.43), total body fat mass (r?=??0.3) and fasting insulin resistance index. A significant positive association (p?<?0.05) was found between testosterone and the quantitative insulin sensitivity check index and high density lipoprotein cholesterol level in serum (r?=?0.26).

Conclusions Low levels of total testosterone, testosterone/estradiol ratio and free androgen index and higher levels of estrone in men with coronary artery disease appear together with many features of metabolic syndrome and may be involved in the pathogenesis of coronary atherosclerosis.     

Age-related changes in musculoskeletal function,balance and mobility measures in men aged 30–80 years

Objectives.?This study aimed to establish age-related changes in musculoskeletal function, balance and mobility measures in men.

Design.?An observational, cross-sectional cohort study was undertaken.

Methods.?One hundred six healthy, community-ambulant men (30–80 years) participated in this study. Recruitment of a convenience sample continued until a minimum of 20 men represented each decade between 30 and 80 years. Demographics (age, height, weight), health and current activity level were recorded. Balance and mobility were measured using the timed up and go test, the step test, functional and lateral reach. Reaction time was determined from limits of stability test. Leg muscle strength was measured with a spring gauge (kg), and ankle flexibility was measured using goniometry.

Results.?Balance, mobility and most strength measures were reduced by the 60s while ankle flexibility declined by the 70s (p?<?0.01). Reaction times increased by the 60s (p?<?0.01).

Conclusion.?This study of men demonstrated reduced musculoskeletal function, balance and mobility generally by the 60s. These results provide health professionals with normal performance levels to use as therapeutic goals as well as identify musculoskeletal factors associated with reducing balance and mobility. Hence, these results inform clinicians and policy makers for the establishment of pre-emptive interventions to promote healthier ageing.