Autophagy and Aging

During the past century, treatments for the diseases of youth and middle age have helped raise life expectancy significantly. However, cognitive decline has emerged as one of the greatest health threats of old age, with nearly 50% of adults over the age of 85 afflicted with Alzheimer's disease. Developing therapeutic interventions for such conditions demands a greater understanding of the processes underlying normal and pathological brain ageing. Recent advances in the biology of ageing in model organisms, together with molecular and systems-level studies of the brain, are beginning to shed light on these mechanisms and their potential roles in cognitive decline.

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Neural mechanisms of ageing and cognitive decline

https://www.healthpromoting.com/sites/default/files/FastingMolecularMechanisms.pdf

Fasting: Molecular Mechanisms and Clinical Applications

Effects of Intermittent Fasting on Health and Aging Evidence is accumulating that eating in a 6-hour period and fasting for 18 hours can trigger a metabolic switch from glucose-based to ketone-base...

https://www.nejm.org/doi/pdf/10.1056/NEJMra1905136

Effects of Intermittent Fasting on Health, Aging, and Disease

Beneficial effects of physical exercise on neuroplasticity and cognition.

Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m(2)) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchanged total fat), and (iii) control. Before and after 3 months of intervention, memory performance was assessed under standardized conditions. We found a significant increase in verbal memory scores after caloric restriction (mean increase 20%; P < 0.001), which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein, most pronounced in subjects with best adherence to the diet (all r values < -0.8; all P values <0.05). Levels of brain-derived neurotrophic factor remained unchanged. No significant memory changes were observed in the other 2 groups. This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects. Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity. Our study may help to generate novel prevention strategies to maintain cognitive functions into old age.

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Caloric restriction improves memory in elderly humans

Background “Presbyphagia” refers to characteristic age-related changes in the complex neuromuscular swallowing mechanism. It has been hypothesized that cumulative impairments in multiple domains affect functional reserve of swallowing with age, but the multifactorial etiology and postulated compensatory strategies of the brain are incompletely understood. This study investigates presbyphagia and its neural correlates, focusing on the clinical determinants associated with adaptive neuroplasticity. Materials and methods 64 subjects over 70 years of age free of typical diseases explaining dysphagia received comprehensive workup including flexible endoscopic evaluation of swallowing (FEES), magnetoencephalography (MEG) during swallowing and pharyngeal stimulation, volumetry of swallowing muscles, laboratory analyzes, and assessment of hand-grip-strength, nutritional status, frailty, olfaction, cognition and mental health. Neural MEG activation was compared between participants with and without presbyphagia in FEES, and associated clinical influencing factors were analyzed. Presbyphagia was defined as the presence of oropharyngeal swallowing alterations e.g., penetration, aspiration, pharyngeal residue pooling or premature bolus spillage into the piriform sinus and/or laryngeal vestibule. Results 32 of 64 participants showed swallowing alterations, mainly characterized by pharyngeal residue, whereas the airway was rarely compromised. In the MEG analysis, participants with presbyphagia activated an increased cortical sensorimotor network during swallowing. As major clinical determinant, participants with swallowing alterations exhibited reduced pharyngeal sensation. Presbyphagia was an independent predictor of a reduced nutritional status in a linear regression model. Conclusions Swallowing alterations frequently occur in otherwise healthy older adults and are associated with decreased nutritional status. Increased sensorimotor cortical activation may constitute a compensation attempt to uphold swallowing function due to sensory decline. Further studies are needed to clarify whether the swallowing alterations observed can be considered physiological per se or whether the concept of presbyphagia may need to be extended to a theory with a continuous transition between presbyphagia and dysphagia.

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Clinical determinants and neural correlates of presbyphagia in community-dwelling older adults

Background The potential of adopting a healthy lifestyle to fight non-communicable diseases (NCDs) is not fully used. We hypothesised that the Healthy Lifestyle Community Programme (HLCP, cohort 1) reduces weight and other risk markers compared with baseline and control. Methods 24-month, non-randomised, controlled intervention trial. Intervention: intensive 8-week phase with seminars, workshops and coaching focusing on a healthy lifestyle (eg, plant-based diet, physical activity, stress management) and group support followed by a 22-month alumni phase. Weight reduction as the primary outcome and other NCD risk parameters were assessed at six time points. Participants were recruited from the general population. Multiple linear regression analyses were conducted. Results 143 participants (58±12 years, 71% female) were enrolled (91 in the intervention (IG) and 52 in the control group (CG)). Groups’ baseline characteristics were comparable, except participants of IG were younger, more often females, overweight and reported lower energy intake (kcal/day). Weight significantly decreased in IG at all follow-ups by −1.5 ± 1.9 kg after 8 weeks to −1.9 ± 4.0 kg after 24 months and more than in CG (except after 24 months). Being male, in the IG or overweight at baseline and having a university degree predicted more weight loss. After the intervention, there were more participants in the IG with a ‘high’ adherence (+12%) to plant-based food patterns. The change of other risk parameters was most distinct after 8 weeks and in people at elevated risk. Diabetes-related risk parameters did not improve. Conclusion The HLCP was able to reduce weight and to improve aspects of the NCD risk profile. Weight loss in the IG was moderate but maintained for 24 months. Participants of lower educational status might benefit from even more practical units. Future interventions should aim to include more participants at higher risk. Trial registration number DRKS00018821.

/pdf/bridging-the-gap-between-science-and-society-long-term-2ihloe1l.pdf

Bridging the gap between science and society: long-term effects of the Healthy Lifestyle Community Programme (HLCP, cohort 1) on weight and the metabolic risk profile: a controlled study

Background: Stress and cortisol dysregulation are linked to NCDs. Moreover, stress favours unhealthy lifestyle patterns, which increase the risk for NCDs. The role of the Cortisol Awakening Response (CAR) and the effect of lifestyle interventions on the same remain unclear. Methods: The impact of the intensive 8-week phase of the Healthy Lifestyle Community Programme (HLCP, cohort 1) on parameters of the CAR, ie cortisol values 0 (sample [S]1), 30), 45 and 60 minutes post-awakening, average peak, S1-peak delta and area under the increase curve (AUCI), and perceived stress levels (PSL) was evaluated in a non-randomized, controlled trial. Covariates of the CAR (eg sleep measures) and irregularities in sampling were assessed. The intervention focussed on stress management, a healthy diet, regular exercise, and social support. Participants were recruited from the general population. Multiple linear regression analyses were conducted. Results: 97 participants (age: 56 ± 10 years; 71% female), with 68 in the intervention group (IG; age: 55 ± 8, 77% female) and 29 participants in the control group (CG; age: 59 ± 12, 59% female), were included in the analysis. The baseline characteristics of both groups were comparable, except participants of IG were younger. On average, the PSL at baseline was low in both groups (IG: 9.7 ± 5.4 points; CG: 8.5 ± 6.9 points; p = .165), but 22% (n = 15) in the IG and 20% (n = 6) in the CG reported a high PSL. Most participants reported irregularities in CAR sampling, eg interruption of sleep (IG: 80% CG: 81%). After 8 weeks, most CAR parameters and the PSL decreased in the IG and CG, resulting in no differences of change between the groups. In the IG only, a decrease of PSL was linked to an increase of CAR parameters, eg AUCI (correlation coefficient = −0.307; p = .017). Conclusion: The HLCP may potentially reduce PSL and change the CAR, but results cannot be clearly attributed to the programme. Methodological challenges and multiple confounders, limit suitability of the CAR in the context of lifestyle interventions. Other measures (eg hair-cortisol) may give further insights. Trial registration: German Clinical Trials Register (DRKS); DRKS00018821; www.drks.de

Eight Weeks of Lifestyle Change: What are the Effects of the Healthy Lifestyle Community Programme (Cohort 1) on Cortisol Awakening Response (CAR) and Perceived Stress?

R. Gellner

Papers

Caloric restriction improves memory in elderly humans

Clinical determinants and neural correlates of presbyphagia in community-dwelling older adults

Bridging the gap between science and society: long-term effects of the Healthy Lifestyle Community Programme (HLCP, cohort 1) on weight and the metabolic risk profile: a controlled study

Eight Weeks of Lifestyle Change: What are the Effects of the Healthy Lifestyle Community Programme (Cohort 1) on Cortisol Awakening Response (CAR) and Perceived Stress?

Correction for: Caloric restriction improves memory in elderly humans