Deregulated Nutrient Sensing and Altered Intercellular Communication

00:00 Next, we look at deregulated nutrient sensing. This is definitely associated with aging.

00:09 Even if we think of the individual as a whole, they are taking in less nutrients than they would be in younger cells. Deregulated nutrient sensing involves multiple different pathways.

00:27 Right now, we’re considering that on the cellular level. So, each of the cells in our body, particularly when we think about metabolism, cellular respiration, and the creation and storage of fuels, if we have fat to be in storage or fat to be released from storage. We will see changes in free fatty acid levels as well as visceral adipose tissue and total body fat compositions. All of these change as we age.

01:03 We also see some of these nutrient sensing pathways changed in muscle tissue, changing the rate of fat oxidation versus protein synthesis, so again an issue with storage and release of nutrients.

01:17 Things are just not timed as efficiently as they used to be. The liver, of course is also involved in these nutrient sensing pathways. This is sort of a paradox because when we consider that older adults tend to intake less food, they are also extracting less from that food.

01:48 Now, there is this hypothesis that I think I alluded to it earlier or mentioned it earlier that the more we eat, the more reactive oxygen species that we produce. There’s a lot of research showing that older adults that are consuming less or anyone consuming less actually, you don’t have to be older, consuming less creates less reactive oxygen species and thus less cellular damage. It’s also well-known that as we increase our exercise, we produce our own endogenous molecules that act to counteract that. So, we can get rid of those reactive oxygen species. As there is a decline in nutrient sensing, this is kind of the paradox.

02:42 As there’s a decline in nutrient sensing, we also tend to age the cells more because they’re getting less of the necessary nutrients and the right balance. So, that creates us a situation where one thing sort of feeds the other and obviously very active areas of research presently in cell biology.

03:07 Next, let’s look at altered intercellular communication. As you could imagine, well, think about for a moment all of the things that you know about cell communication. What cells come to mind when you think about cell communication? What types of signaling come to mind when you think about cell communication? I’m sure that a plethora of things came to mind as you think about all these different protein cascades and signaling between cells, signal molecules activating other cascades within cells. So lots of different things become less efficient as cells age. Particularly, you might have thought about neurons because they’re definitely signaling cells and neuro-hormonal signaling that occurs between neurons. Definitely as cells age, this signaling becomes deregulated.

04:10 We see certain evidence of this as we aggregate cells in whole organs in the aging process.

04:17 In addition to the signaling between neurons, one of the areas that we see a lot of action, so to speak, is in inflammatory reactions. The immune system cells are not necessarily talking to each other in the way that they would be in a younger cell lineage. So, we are deregulating intercellular signaling in that manner also. When we consider the inflammatory reactions increasing, we also can see that they are going to deregulate cell signaling including things like adrenergic signaling, so these things become slower. Renin-angiotensin system, you should be familiar with most of these from your understanding of physiology as well as insulin and IGF signaling and immunosurveilance.

05:21 All of these categories of signaling become deregulated based on some of the inflammatory reactions.

05:30 Now, another concept that we haven’t really spent any time looking at is the communication of cells through gap junctions and the concept of bystander effect which is sort of like contagious aging where through gap junctions, as you know gap junctions allow free passage of ingredients or materials between cells. So, what is in the environment of one cell will move through a gap junction into another cell. So, you could see how essentially we’re letting these qualities of aging pass from one cell to another. It’s noted that when one cell ages, cells in its neighborhood tend to age also. The bystander effect is something you should be familiar with in aging.

06:23 Contagious aging, that’s how I will keep that in mind.