Circadian rhythms persist without transcription in a eukaryote

Circadian rhythms are ubiquitous in eukaryotes, and coordinate numerous aspects of behaviour, physiology and metabolism, from sleep/wake cycles in mammals to growth and photosynthesis in plants. This daily timekeeping is thought to be driven by transcriptionaltranslational feedback loops, whereby rhythmic expression of clock- gene products regulates the expression of associated genes in approximately 24-hour cycles. The specific transcriptional components differ between phylogenetic kingdoms. The unicellular pico-eukaryotic alga Ostreococcus tauri possesses a naturally minimized clock, which includes many features that are shared with plants, such as a central negative feedback loop that involves the morning-expressed CCA1 and evening-expressed TOC1 genes. Given that recent observations in animals and plants have revealed prominent post-translational contributions to timekeeping, a reappraisal of the transcriptional contribution to oscillator function is overdue. Here we show that non-transcriptional mechanisms are sufficient to sustain circadian timekeeping in the eukaryotic lineage, although they normally function in conjunction with transcriptional components. We identify oxidation of peroxiredoxin proteins as a transcription-independent rhythmic biomarker, which is also rhythmic in mammals. Moreover we show that pharmacological modulators of the mammalian clock mechanism have the same effects on rhythms in Ostreococcus. Post-translational mechanisms, and at least one rhythmic marker, seem to be better conserved than transcriptional clock regulators. It is plausible that the oldest oscillator components are non-transcriptional in nature, as in cyanobacteria, and are conserved across kingdoms

A randomized controlled trial of Kundalini yoga in mild cognitive impairment.

BACKGROUND: Global population aging will result in increasing rates of cognitive decline and dementia. Thus, effective, low-cost, and low side-effect interventions for the treatment and prevention of cognitive decline are urgently needed. Our study is the first to investigate the effects of Kundalini yoga (KY) training on mild cognitive impairment (MCI). METHODS: Older participants (≥55 years of age) with MCI were randomized to either a 12-week KY intervention or memory enhancement training (MET; gold-standard, active control). Cognitive (i.e. memory and executive functioning) and mood (i.e. depression, apathy, and resilience) assessments were administered at baseline, 12 weeks and 24 weeks. RESULTS: At baseline, 81 participants had no significant baseline group differences in clinical or demographic characteristics. At 12 weeks and 24 weeks, both KY and MET groups showed significant improvement in memory; however, only KY showed significant improvement in executive functioning. Only the KY group showed significant improvement in depressive symptoms and resilience at week 12. CONCLUSION: KY group showed short- and long-term improvements in executive functioning as compared to MET, and broader effects on depressed mood and resilience. This observation should be confirmed in future clinical trials of yoga intervention for treatment and prevention of cognitive decline (NCT01983930)

Health related quality of life in an at‐risk population during an intervention study and extended follow‐up ‐ the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)

AbstractBackgroundThe multidomain lifestyle intervention in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed positive effects on health‐related quality of life (HRQL) during the 2‐year intervention, particularly physical functioning. Our aim was to study how these benefits were maintained over an extended follow‐up.MethodA total of 1259 older adults aged 60‐77 were randomized into multidomain intervention (n = 631) or control groups (n = 628). A validated HRQL scale RAND‐36 with 8 subscales was collected during the original 2‐year intervention (0,1,2 yrs) and during the 11‐year extended follow‐up (7,11 yrs). Emotional well‐being subscale was also available from a mail survey during the COVID19 pandemic (approx. 9 yrs). Changes over time and intervention effect on HRQL were analyzed using mixed‐effects regression.ResultAltogether 1212 (96%) provided HRQL data at baseline, 1069 (85%) after the intervention, and 501 after 11 years (40%). During the follow‐up mean RAND total score decreased from 76.4 to 69.3 All subscales were below baseline after 7 years, and physical functioning subscales started to decline already after 2 years (physical functioning, role limitations due to physical health, and bodily pain). Intervention related improvement in general health perception at the 1st year was maintained up to 11 years (p‐value for difference in change between groups 0.002), but improvement in physical functioning subscales vanished over time. Emotional well‐being started to decline at the 7‐year visit, without group differences. It temporarily improved during the pandemic (p‐value for change from the 7‐year visit 0.001) but declined back at the 11‐year visit.ConclusionOverall HRQL declined over time, as expected with aging. A 2‐year multidomain lifestyle intervention among at‐risk older adults resulted in sustained difference in general health perception, which is an important marker of general health. Lesser decline in physical functioning observed during the intervention was not sustained during the extended follow‐up. In the whole group, emotional well‐being declined later than physical functioning. Temporary improvement during the pandemic could be explained by the timing of the questionnaire (right after lifting restrictions), but it indicates that rapid changes due to external factors have an impact on emotional well‐being of older people.</sec