Fight Aging!

Upregulation of LAMP2A is capable of improving the operation of chaperone-mediated autophagy in later life. A while back researchers demonstrated meaningfully improved liver function in mice via this mechanism. Here, they start from the same point of LAMP2A and autophagy in order to try to address the age-related faltering of the hematopoietic system responsible for producing red blood cells and immune cells. With age hematopoietic stem cells become damaged and change their behavior in ways that degrade immune function, such as be producing too many myeloid cells and too few lymphoid cells. Can this be addressed to some degree by upregulation of chaperone-mediated autophagy? The evidence is suggestive.

Creating 200 billion-plus brand-new red blood cells a day can take a toll on a body. The capacity to replace components charged with the life-sustaining task of carrying oxygen eventually wears out with aging, resulting in health problems, from anemia to blood cancers. What if we could halt the aging process and maintain young blood cells for life? With blood cells making up a whopping 90% of the body's cells, it makes sense that keeping them abundant and fit could boost vitality into our golden years.

Blood cells are responsible for oxygen transport, infection control, and many other things scientists are just discovering. But they have a short lifespan - 120 days for red blood cells, and even shorter for other blood cells - and must regenerate continuously throughout life, he said. "This fascinating phenomenon is made possible by the capacity of hematopoietic stem cells (HSCs) to multiply and differentiate into all the blood cell types, a mechanism that unfortunately can become impaired as we get old. Results can include anemia, when we can't make enough red blood cells, or blood cancers, when some blood cell precursors go rogue and start multiplying without differentiating,"

The researchers targeted chaperone-mediated autophagy (CMA), one mechanism they found responsible for the degradation. Like a housekeeper gone awry, CMA with age can fail in its job of cleaning up damaged proteins and other wastes, sabotaging the HSCs' capacity to make new, healthy blood cells. Pinpointing one key protein (LAMP2A) that regulates CMA function whose expression and activity declines with age, the scientists used both genetic, dietary and pharmacological interventions that restored young hematopoiesis (formation of blood cellular components) in old laboratory mice.

The scientists also showed that a metabolic enzyme (FADS2) involved in fatty acid metabolism loses function with age, reducing healthy blood cell formation. By introducing gamma linolenic acid (GLA), a product of the failing enzyme, in the rodents' diets, the researchers again improved cell regeneration. After determining that the CMA dysfunctions in mice mirrored those in 70-plus-year-old humans, the researchers believe their findings could eventually translate into reversing the aging process of HSCs in humans, opening the door to numerous medical therapies.

Link: https://news.cuanschutz.edu/news-stories/scientists-discover-ways-of-making-old-blood-new-again