Heat Shock Protein Delivered as a Therapy Slows Aging in Mice

Heat shock proteins are involved in cellular quality control mechanisms that ensure correct functioning of proteins and the removal of damaged protein machinery. Research has demonstrated that more heat shock protein activity is a good thing. More quality control means less damage, and less damage means fewer secondary effects of that damage and, ultimately, a longer life. This is the way it works out in the numerous methods of modestly slowing aging in laboratory animals in which greater cellular repair and maintenance occurs as a result of the intervention. Calorie restriction is perhaps the most studied, but there are many others these days. There has been some interest in the research community in harnessing aspects of cellular quality control processes for therapeutic use, but little progress towards clinical applications. In that context, the research here is a perhaps surprisingly direct application of the principle to show benefits:

Molecular chaperone Heat Shock Protein 70 (Hsp70) plays an important protective role in various neurodegenerative disorders often associated with aging, but its activity and availability in neuronal tissue decrease with age. The compromised ability of neurons to express Hsp70 correlates with aging-related neurodegeneration. Here we explored the effects of intranasal administration of exogenous recombinant human Hsp70 (eHsp70) on lifespan and neurological parameters in middle-aged and old mice. Long-term administration of eHsp70 significantly enhanced the lifespan of animals of different age groups. Behavioral assessment after 5 and 9 mo of chronic eHsp70 administration demonstrated improved learning and memory in old mice. Likewise, the investigation of locomotor and exploratory activities after eHsp70 treatment demonstrated a significant therapeutic effect of this chaperone. Measurements of synaptophysin show that eHsp70 treatment in old mice resulted in larger synaptophysin-immunopositive areas and higher neuron density compared with control animals. Furthermore, eHsp70 treatment decreased accumulation of lipofuscin, an aging-related marker, in the brain and enhanced proteasome activity.

In summary, Hsp70 treatment extended mean and maximum lifespan, improved learning and memory in old animals, increased curiosity, decreased anxiety, and helped maintain synaptic structures that degrade with age. These results provide evidence that intranasal administration of Hsp70 could have significant therapeutic potential in preserving brain tissue and memory for middle-age and old individuals and could be applied either as unique self-contained treatment or in combination with other pharmacological therapies.

Link: http://dx.doi.org/10.1073/pnas.1516131112

Comments

I fast for two consecutive days each week to slow down the aging process. (After I eat supper on Friday I won't eat again until Monday morning.) I'll drink liquids during that time but nothing with added sugar. I avoid sugar during the days I eat, also. I'm 72, I exercise daily, and my hair hasn't turned gray yet. I've avoided major diseases such as heart problems and cancer, undoubtedly due at least in part, to the fasting. In the last few hours of a two day fast I feel as if cobwebs are being removed from my body. Try that fasting. It will be difficult, but see how your body feels as a consequence.

Posted by: Dan Gollub at October 11th, 2016 5:15 PM

"Treatment with eHsp70 improved longevity from 29 to 31 mo in both age groups, but more importantly, eHsp70 improved survival rates; at 22 mo, 55.5% of animals in the experimental middle-aged group were alive, compared with 22.2% in the control group. After 22 mo, in the untreated old-age group, survival was just over 35.2%, whereas in the experimental group, 54.5% were still alive."

The mean LE is nice, and if my math is right, the max LE is about 9%. Heat shock proteins are definitely something to keep an eye on.

Posted by: KC at October 12th, 2016 3:50 PM

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