Fight Aging!

Researchers here note a modest life extension in mice resulting from long-term treatment with low doses of a PPARγ agonist drug, started in mid-life. This is thought to be an adjustment that acts to suppress inflammation and improve insulin metabolism, both strongly connected to the way in which cellular metabolism determines pace of aging. The size of the effect in mice is small enough to think that it would have little effect on life span in our species, however. Effects derived from this sort of metabolic adjustment have a much larger impact on life span in short-lived species than they do in long-lived species, as most of the relevant stress response mechanisms connecting metabolism to environmentally induced variations in the pace of aging evolved as a part of the life-extending response to calorie restriction. A seasonal famine is a long time to a mouse, not so long to a human, so only the mouse evolves a sizable gain in life span when these stress response mechanisms are trigger.

Aging leads to a number of disorders caused by cellular senescence, tissue damage, and organ dysfunction. It has been reported that anti-inflammatory and insulin-sensitizing compounds delay, or reverse, the aging process and prevent metabolic disorders, neurodegenerative disease, and muscle atrophy, improving healthspan and extending lifespan. Here we investigated the effects of PPARγ agonists in preventing aging and increasing longevity, given their known properties in lowering inflammation and decreasing glycemia.

Our molecular and physiological studies show that long-term treatment of mice at 14 months of age with low doses of the PPARγ ligand rosiglitazone (Rosi) improved glucose metabolism and mitochondrial functionality. These effects were associated with decreased inflammation and reduced tissue atrophy, improved cognitive function, and diminished anxiety- and depression-like conditions, without any adverse effects on cardiac and skeletal functionality. Furthermore, Rosi treatment of mice started when they were 14 months old was associated with an 11% median lifespan extension.

A retrospective analysis of the effects of the PPARγ agonist pioglitazone (Pio) on longevity showed decreased mortality in patients receiving Pio compared to those receiving a PPARγ-independent insulin secretagogue glimepiride. Taken together, these data suggest the possibility of using PPARγ agonists to promote healthy aging and extend lifespan.

Link: https://doi.org/10.1111/acel.13267