Daily ingestion of Akkermansia mucciniphila for one month promotes healthy aging and increases lifespan in old female mice

Abstract In older humans, multiple chronic diseases and increased life expectancy impose a disproportionate socioeconomic burden. Dietary interventions are valuable strategies for promoting healthy aging. Caloric restriction (CR) without malnutrition is a robust intervention able to delay disease onset and increase survival in model organisms. However, the impracticability of chronic CR outweighs the potential long-term benefits in humans. Time-restricted feeding (TRF), i.e. the limitation in the timing of food intake without necessarily reducing caloric intake, can protect against metabolic disorders through the synchronization of the circadian rhythm. This study compares whether limiting access to ad libitum (AL) food for a few hours per day mimics the beneficial effects of a CR diet. A large cohort of C57BL/6J female mice (n=250) was distributed into five feeding paradigms at midlife: AL, TRF for 8 hours, TRF for 4 hours, 20% CR and 20% CR fed twice a day (CRx2). Pathological analyses at death reveal a shift in fatal neoplasms toward an older age in TRF8 mice. AL mice had the highest prevalence of tumors (93%) and TRF4 had the lowest (77%). The highest tumor burden was observed in AL mice while CRx2 animals had the lowest number of neoplasms. Histiocytic sarcoma and lymphoma were the most represented malignancies, with CR mice exhibiting the highest rate of histiocytic sarcoma (75%) and the lowest rate of lymphoma (10%). These results indicate that time- and calorie-restricted feeding regimens can slow down malignant neoplasm progression and extend health span in female mice, even when started in adulthood.

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Effects of the Clock Modulator Nobiletin on Circadian Rhythms and Pathophysiology in Female Mice of an Alzheimer’s Disease Model

Biomolecules ◽

10.3390/biom11071004 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1004

Author(s):

Eunju Kim ◽

Kazunari Nohara ◽

Marvin Wirianto ◽

Gabriel Escobedo ◽

Ji Ye Lim ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Circadian Rhythms ◽

Healthy Aging ◽

Neurodegenerative Disorder ◽

Amyloid Β ◽

Co2 Production ◽

Altered Expression ◽

Female Mice ◽

Age Related

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder and the most common cause of dementia. Various pathogenic mechanisms have been proposed to contribute to disease progression, and recent research provided evidence linking dysregulated circadian rhythms/sleep and energy metabolism with AD. Previously, we found that the natural compound Nobiletin (NOB) can directly activate circadian cellular oscillators to promote metabolic health in disease models and healthy aging in naturally aged mice. In the current study, using the amyloid-β AD model APP/PS1, we investigated circadian, metabolic and amyloid characteristics of female mice and the effects of NOB. Female APP/PS1 mice showed reduced sleep bout duration, and NOB treatment exhibited a trend to improve it. While glucose tolerance was unchanged, female APP/PS1 mice displayed exaggerated oxygen consumption and CO2 production, which was mitigated by NOB. Likewise, cold tolerance in APP/PS1 was impaired relative to WT, and interestingly was markedly enhanced in NOB-treated APP/PS1 mice. Although circadian behavioral rhythms were largely unchanged, real-time qPCR analysis revealed altered expression of several core clock genes by NOB in the cerebral cortex, notably Bmal1, Npas2, and Rora. Moreover, NOB was also able to activate various clock-controlled metabolic genes involved in insulin signaling and mitochondrial function, including Igf1, Glut1, Insr, Irs1, Ucp2, and Ucp4. Finally, we observed that NOB attenuated the expression of several AD related genes including App, Bace1, and ApoE, reduced APP protein levels, and strongly ameliorated Aβ pathology in the cortex. Collectively, these results reveal novel genotype differences and importantly beneficial effects of a natural clock-enhancing compound in biological rhythms and related pathophysiology, suggesting the circadian clock as a modifiable target for AD.

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Central forebrain Fos responses to familiar male odours are attenuated in recently mated female mice

European Journal of Neuroscience ◽

10.1046/j.1460-9568.2001.01382.x ◽

2001 ◽

Vol 13 (2) ◽

pp. 389-399 ◽

Cited By ~ 1

Author(s):

Heather A. Halem ◽

James A. Cherry ◽

Michael J. Baum

Keyword(s):

Female Mice ◽

Mated Female

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Complementary Effects of Multivitamin and Omega-3 Fatty Acid Supplementation on Indices of Cardiovascular Health in Individuals with Elevated Homocysteine

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000093 ◽

2012 ◽

Vol 82 (1) ◽

pp. 41-52 ◽

Cited By ~ 5

Author(s):

P. Earnest ◽

S. Kupper ◽

M. Thompson ◽

Guo ◽

S. Church

Keyword(s):

Risk Factors ◽

Cardiovascular Health ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

C Reactive Protein ◽

Fatty Acid Supplementation ◽

Omega 3 Fatty Acid ◽

Reactive Protein ◽

Daily Ingestion

Homocysteine (HCY), C-reactive protein (hsCRP), and triglycerides (TG) are risk factors for cardiovascular disease (CVD). While multivitamins (MVit) may reduce HCY and hsCRP, omega-3 fatty acids (N3) reduce TG; yet, they are seldom studied simultaneously. We randomly assigned 100 participants with baseline HCY (> 8.0 umol/L) to the daily ingestion of: (1) placebo, (2) MVit (VitC: 200 mg; VitE: 400 IU; VitB6: 25 mg; Folic Acid: 400 ug; VitB12: 400 ug) + placebo, (3) N3 (2 g N3, 760 mg EPA, 440 mg DHA)+placebo, or (4) MVit + N3 for 12 weeks. At follow-up, we observed significant reductions in HCY (umol/L) for the MVit (- 1.43, 95 %CI, - 2.39, - 0.47) and MVit + N3 groups (- 1.01, 95 %CI, - 1.98, - 0.04) groups, both being significant (p < 0.05) vs. placebo (- 0.57, 95 %CI, - 1.49, 0.35) and N3 (1.11, 95 % CI, 0.07, 2.17). hsCRP (nmol/L) was significantly reduced in the MVit (- 6.00, 95 %CI, - 1.04, - 0.15) and MVit + N3 (- 0.98, 95 %CI, - 1.51, - 0.46) groups, but not vs. placebo (- 0.15, 95 %CI, - 0.74, 0.43) or N3 (- 0.53, 95 %CI, - 1.18, 0.12). Lastly, we observed significant reductions in TG for the N3 (- 0.41, 95 %CI, - 0.69, - 0.13) and MVit + N3 (- 0.71, 95 %CI, - 0.93, - 0.46) groups, both significant vs. placebo (- 0.10, 95 %CI, - 0.36, 0.17) and MVit groups (0.15, 95 %CI, - 12, 0.42). The co-ingestion of MVit + N3 provides synergistic affects on HCY, hsCRP, and plasma TG.

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Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽

10.1024/1662-9647/a000074 ◽

2012 ◽

Vol 25 (4) ◽

pp. 235-245 ◽

Cited By ~ 64

Author(s):

Katja Franke ◽

Christian Gaser

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Healthy Aging ◽

Brain Aging ◽

Elderly Subjects ◽

Additional Increase ◽

Longitudinal Changes ◽

Novel Method ◽

The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

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Psychophysiological Responses to Stress Related to Anxiety in Healthy Aging

Journal of Psychophysiology ◽

10.1027/0269-8803/a000221 ◽

2019 ◽

Vol 33 (3) ◽

pp. 188-197 ◽

Cited By ~ 2

Author(s):

Roberta Adorni ◽

Agostino Brugnera ◽

Alessia Gatti ◽

Giorgio A. Tasca ◽

Kaoru Sakatani ◽

...

Keyword(s):

Healthy Aging ◽

Near Infrared ◽

Response Times ◽

Cognitive Resources ◽

Stressful Condition ◽

Healthy Elderly ◽

Situational Stress ◽

Anxiety Response ◽

Nirs Signal ◽

Psychophysiological Correlates

Abstract. The aim of the study was to explore the effects of situational stress and anxiety in a group of healthy elderly, both in terms of psychophysiological correlates and cognitive performance. Eighteen participants ( Mage = 70 ± 6.3; range 60–85) were assessed for anxiety and were instructed to perform a computerized math task, under both a stressful and a control condition, while near-infrared spectroscopy (NIRS) signal and electrocardiography (ECG) were recorded. NIRS results evidenced an increased activation of right PFC during the entire procedure, even if effect sizes between left and right channels were larger during the experimental condition. The amount of right activation during the stressful condition was positively correlated with anxiety. Response times (RTs) were slower in more anxious than in less anxious individuals, both during the control and stressful conditions. Accuracy was lower in more anxious than in less anxious individuals, only during the stressful condition. Moreover, heart rate (HR) was not modulated by situational stress, nor by anxiety. Overall, the present study suggests that in healthy elderly, anxiety level has a significant impact on cerebral responses, and both on the amount of cognitive resources and the quality of performance in stressful situations.

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Prospective Memory Development Across the Lifespan

European Psychologist ◽

10.1027/1016-9040/a000380 ◽

2020 ◽

Vol 25 (3) ◽

pp. 162-173 ◽

Cited By ~ 1

Author(s):

Sascha Zuber ◽

Matthias Kliegel

Keyword(s):

Prospective Memory ◽

Healthy Aging ◽

Present Model ◽

Current Knowledge ◽

Well Being ◽

The Elderly ◽

Cognitive Factors ◽

Everyday Functioning ◽

Integrative Framework

Abstract. Prospective Memory (PM; i.e., the ability to remember to perform planned tasks) represents a key proxy of healthy aging, as it relates to older adults’ everyday functioning, autonomy, and personal well-being. The current review illustrates how PM performance develops across the lifespan and how multiple cognitive and non-cognitive factors influence this trajectory. Further, a new, integrative framework is presented, detailing how those processes interplay in retrieving and executing delayed intentions. Specifically, while most previous models have focused on memory processes, the present model focuses on the role of executive functioning in PM and its development across the lifespan. Finally, a practical outlook is presented, suggesting how the current knowledge can be applied in geriatrics and geropsychology to promote healthy aging by maintaining prospective abilities in the elderly.

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