Current Aging Science - Volume 11, Issue 2, 2018

Background: A growing body of epidemiologic evidence suggests that neurodegenerative diseases occur less frequently in cancer survivors, and vice versa. While unusual, this inverse comorbidity is biologically plausible and could be explained, in part, by the evolutionary tradeoffs made by neurons and cycling cells to optimize the performance of their very different functions. The two cell types utilize the same proteins and pathways in different, and sometimes opposite, ways. However, cancer and neurodegeneration also share many pathophysiological features. Objective: In this review, we compare three overlapping aspects of neurodegeneration and cancer. Method: First, we contrast the priorities and tradeoffs of dividing cells and neurons and how these manifest in disease. Second, we consider the hallmarks of biological aging that underlie both neurodegeneration and cancer. Finally, we utilize information from genetic databases to outline specific genes and pathways common to both diseases. Conclusion: We argue that a detailed understanding of the biologic and genetic relationships between cancer and neurodegeneration can guide future efforts in designing disease-modifying therapeutic interventions. Lastly, strategies that target aging may prevent or delay both conditions.

Background: Dementias due to neurodegenerative disorders and more specifically, Alzheimer’s disease (AD) are the most frequent of all diseases within the industrialized world. Besides this alarming fact, it is noted too that almost three-quarter of people with AD reside in low or middle- income nations. In recent years, cognitive and behavioral neuroscientists have focused on a possible correlation between environmental agents and genetic risk factors for these dementias. Methods: In this narrative review, a close review of Medical Literature Analysis and Retrieval System was conducted. The authors aimed at analyzing possible interactions between lifestyle patterns and major risk factors responsible for cognitive decline and dementia, considering that the prevention or treatment of midlife modifiable risks may possibly reduce population-wide late-life pathological neurodegeneration. Results: This review focuses on modifiable risk factors for late-life cognitive decline. A growing number of studies have indicated that the impact of genetics and epigenetic factors on dementia risk is dependent on different lifestyle factors, ranging from leisure activities and nutritional habits, through to social interaction and toxic exposure. Conclusion: Despite all evidence regarding modifiable risk factors possibly reducing the risk of developing dementia in later life, many unanswered questions remain regarding the direct influence of these variables in later life. People who regularly and actively participate in different lifelong activities (social, cultural and intellectual) do tend to perform better on formal cognitive tests, experience fewer cognitive complaints, and are less likely to develop neurodegenerative disorders.

Humans have long sought means to extend longevity and counteract the effects of aging on physical and mental functioning. Exercise is a highly effective way of treating and preventing the main causes of morbidity and mortality, most of which are associated with aging. Interestingly, the Klotho gene is involved in the aging process. Indeed, overexpression of the Klotho gene is associated with longevity, and experimental animals lacking this gene seem to develop multiple disorders resembling human aging and present a shortened lifespan. Three Klotho-related genes have been identified: α-Klotho, β-Klotho, and γ-Klotho. Exercise seems to play a key role on the secreted form of the α-Klotho gene (S-Klotho) in animal models as well as in humans. We systematically reviewed the available evidence on the associations between exercise and S-Klotho protein regulation.

Background: Deterioration in vestibular function occurs with ageing and is linked to age-related falls. Sensory hair cells located in the inner ear vestibular labyrinth are critical to vestibular function. Vestibular hair cells rely predominantly on oxidative phosphorylation (OXPHOS) for energy production and contain numerous mitochondria. Mitochondrial DNA (mtDNA) mutations and perturbed energy production are associated with the ageing process. Objective: We investigated the effects of ageing on mtDNA in vestibular hair and support cells, and vestibular organ gene expression, to better understand mechanisms of age-related vestibular deficits. Methods: Vestibular hair and supporting cell layers were microdissected from young and old rats, and mtDNA was quantified by qPCR. Additionally, vestibular organ gene expression was analysed by microarray and gene set enrichment analyses. Results: In contrast to most other studies, we found no evidence of age-related mtDNA deletion mutations. However, we found an increase in abundance of major arc genes near the mtDNA control region. There was also a marked age-related reduction in mtDNA copy number in both cell types. Vestibular organ gene expression, gene set enrichment analysis showed the OXPHOS pathway was down regulated in old animals. Conclusion: Given the importance of mtDNA to mitochondrial OXPHOS and hair cell function, our findings suggest the vestibular organs are potentially on the brink of an energy crisis in old animals.

Background: Immunosenescence is a remodeling of the immune system, caused by aging, with changes in the function of neutrophils, lymphocytes, and Treg cells. Objective: This study aimed to evaluate the expression of molecules CD11b, CD16 and CD64 (neutrophils), CD154 (T lymphocytes), CD40 (B lymphocytes), and to quantitatively analyze the Treg cell subpopulation. Methods: 49 elderlies (≥60 years) and 49 adults (≤35 years) were studied. Flow cytometry was used to analyze the expression of surface molecules and the subpopulation of Treg cells, and the results between the groups were compared statistically by the t-test. Results: There was a decreased significance in the expression of CD11b and CD40 in the elderly. Conclusion: Decreased CD11b expression can result in susceptibility to infectious diseases, and impairment of phagocytic capacity. Decreased CD40 expression can result in a decline in B lymphocyte activation. The other molecule studied presented alterations not significant, but compatible with the immunological changes in aging.

Background: Dehydroepiandrosterone (DHEA) is an important precursor of active steroid hormone, produced abundantly by the adrenal cortex with an age-dependent pattern. Objective: We investigated whether chronic DHEA administration impacts on redox status and on Akt protein activation in skeletal muscle during the aging process (3 and 24 months-old rats). Methods: Rats received one weekly dose/5 weeks of DHEA (10 mg/kg) or vehicle. Gastrocnemius muscle was removed to evaluate glutathione system, hydrogen peroxide, antioxidant enzymes, and expression of Akt kinase protein. Results: In the 3-months-old rats DHEA induced an increase in hydrogen peroxide when compared both to its control (276%) and the 24-months-old DHEA group (485%). Moreover, in the 24- months-old rats DHEA caused an increase in GSSG (41 and 28%), a decrease in reduced-GSH (55 and 51%), and a more oxidized redox status (reduction in GSH/GSSG ratio, 47 and 65 %) when compared to 3-month-old DHEA and to 24-months-old control groups, respectively. Both older groups had increased G6PDH (2.7 fold) and GST (1.7 fold) activities when compared to younger groups, independently of any DHEA treatment. However, there was no modulation of Akt protein (phosphorylated/total isoform). Conclusion: The results show that chronic DHEA administration to 3 and 24-months-old rats may not present positive effects regarding the redox environment in skeletal muscle without modulation of pro-survival Akt kinase. Due to the large-scale self-administration of DHEA as an “anti-aging” dietary supplement, it is crucial to investigate its molecular mechanisms over oxidative stressinduced related diseases.

Background: Acute Systemic Diseases (ASD) impact on extended leukoaraiosis (ExLA) have been seldom described. We study the deterioration in daily life activities (DLA) and cognition associated with ASD events compared with the well-described impacts of stroke in patients with leukoaraiosis (L-A). Methods: Cross-sectional surveys of aged adults from the emergency room after an acute event of ASD or stroke, hospitalized or receiving home care, were followed for one year. From 268 initial patients 206 were included in the study, all with moderate to severe L-A (Fazekas 2 and 3). The Clinical Deterioration Rating (CDR) and the modified Rankin scale with structured interview were obtained one week previous to admission and after 3 and 12 months of evolution. Comparisons were conducted within and between groups with nonparametric techniques. Results: We formed three groups of similar age, A: Inpatients with one Stroke, B: Inpatients with one ASD, and C: Outpatients with one ASD. A sudden deterioration in Rankin was evident in Group A, while in B and C impairment was progressive. Impairment in CDR was smooth in all groups while in Rankin it was always greater than in cognition (CDR). No differences were found in the associations between groups and risk factors, hypertension being the most frequent one. Conclusion: ASD in ExL-A causes a worsening of DLA and cognition similar to that observed in ExL-A with concomitant stroke indicating the need, in ageing patients, of differential diagnosis in order to achieve the best possible treatment.

Background: This paper describes a pilot study to assess the feasibility of a novel intervention to improve the management of hypertension among older people in rural South Africa. Older South Africans have the highest rates of uncontrolled hypertension recorded for any country. Notably, South Africa has a widely-available old age grant (pension), which is delivered on a monthly basis to citizens living in rural villages. Methods: We assessed the feasibility of engaging with older people at the point of pension delivery in the Agincourt sub-district of Mpumalanga Province. This included providing information about hypertension, measuring blood pressure, referral to primary care services, and providing a monthly supply of low sodium salt. We recruited 20 people aged 60 and over to participate in the pilot intervention, which was conducted over three months in two villages. Towards the end of the intervention, we conducted focus groups with study participants and held a meeting with local stakeholders, including the district health office and the state social security agency. Results: The pilot study demonstrated (i) Sustained engagement with the original 20 participants. Of these, 19 continued to participate in the intervention during subsequent monthly pension days. (ii) A high level of acceptance of the low sodium salt product reflected in repeat usage and comments made in the focus groups. (iii) Strong support for the intervention and a willingness to collaborate with local stakeholders. (iv) A perception among participants that symptoms they associated with hypertension had abated. This is supported by blood pressure readings made over the three months of follow-up. Conclusion: Though limited in scope, this pilot study provided evidence of the feasibility of the intervention and justification for it to be tested on a larger and more robust basis.