Restoring metabolism of myeloid cells reverses cognitive decline in ageing [Scholarly Article - Nature, 2021]

Title:

Restoring metabolism of myeloid cells reverses cognitive decline in ageing 

 

Authors:

Paras S. Minhas, Amira Latif-Hernandez, Melanie R. McReynolds, Aarooran S. Durairaj, Qian Wang, Amanda Rubin, Amit U. Joshi, Joy Q. He, Esha Gauba, Ling Liu, Congcong Wang, Miles Linde, Yuki Sugiura, Peter K. Moon, Ravi Majeti, Makoto Suematsu, Daria Mochly-Rosen, Irving L. Weissman, Frank M. Longo, Joshua D. Rabinowitz & Katrin I. Andreasson    

 

Published:

Nature, 20 January 2021

https://www.nature.com/articles/s41586-020-03160-0

 

Abstract:

Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty1,2,3. The ageing brain is also vulnerable to inflammation, as demonstrated by the high prevalence of age-associated cognitive decline and Alzheimer’s disease4,5,6. Systemically, circulating pro-inflammatory factors can promote cognitive decline7,8, and in the brain, microglia lose the ability to clear misfolded proteins that are associated with neurodegeneration9,10. However, the underlying mechanisms that initiate and sustain maladaptive inflammation with ageing are not well defined. Here we show that in ageing mice myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation11. In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. In aged mice, inhibition of myeloid EP2 signalling rejuvenates cellular bioenergetics, systemic and brain inflammatory states, hippocampal synaptic plasticity and spatial memory. Moreover, blockade of peripheral myeloid EP2 signalling is sufficient to restore cognition in aged mice. Our study suggests that cognitive ageing is not a static or irrevocable condition but can be reversed by reprogramming myeloid glucose metabolism to restore youthful immune functions.

 

For better health, don't sleep your age: Older people with ‘young’ sleep patterns have more robust cognition than those whose rest is typical for their age [Nature, 17 Nov 2020]

Title:

For better health, don't sleep your age: Older people with ‘young’ sleep patterns have more robust cognition than those whose rest is typical for their age

 

Published:

Nature, 17 November 2020

https://www.nature.com/articles/d41586-020-03244-x

From the article:

Shaun Purcell at Harvard Medical School in Boston, Massachusetts, and his colleagues tracked the sleep of 3,819 people between 54 and 96 years old by recording their brain waves through electroencephalogram sensors that the participants wore throughout the night. The researchers then scored each person’s sleep for more than 150 sleep characteristics and brain-activity patterns. These included factors such as sleep disturbance, the length of the sleep cycles in which dreams occur and preference for mornings or evenings.

See also:

Macro and micro sleep architecture and cognitive performance in older adults

By Ina Djonlagic, Sara Mariana, Annette L. Fitzpatrick [et al.]

Nature Human behaviour, 16 November 2020