Cell Aging: Molecular Damage Control PDF

**Cell aging** Aging - a biological process resulting in a decline in physical function that is induced by accumulating damage in cells. But what is happening inside of our body that leads to aging? We know from cell cultures that cells start to look different as they age (see right). The followi...

**Cell aging** Aging - a biological process resulting in a decline in physical function that is induced by accumulating damage in cells. But what is happening inside of our body that leads to aging? We know from cell cultures that cells start to look different as they age (see right). The following questions will be answered: - - - - In order to answer these questions, it's important to understand how decisions inside of the body are made: **the functioning and fate of cells is determined by neighboring cells and by signaling molecules.** **[Organelles and their functions]** - - -  When there is too much ER stress coupled with environmental/genetic factors: ER stress → accumulation of oxidized, misfolded, cross-linked, or aggregated protein molecules → deleterious effects on cellular homeostasis and on tissue and organ integrity → progressive decline in cellular integrity leads to aging, disease, and ultimately, to death. - - - - - - - -  After a while, a combination of these damaging processes leads to cellular senescence (see the diagrams below) which means a malfunctioning of the cell, impairment of the regenerative capacity of the cell, the production of inflammation signals and detrimental signals to neighboring cells as well as breakdown of the extracellular fluid (ECM). Senescence is a process: 1. a. 2. b. 3. c. d. **Threshold theory of senescent cell accumulation** = once senescent cell burden exceeds a threshold, the self-amplifying paracrine and endocrine spread of senescence through the SASP overcomes immune clearance → progressive chronic disease and comorbidity. [So what can we do about it?] 1. a. 2. b. c. 3. It's difficult to build good interventions for senescence because of the amount of different inducers of senescence, different SASP types, different gene pathways involved and different tissues in the body. **Immune system** There are two main parts of the human immune system: innate and adaptive. 1. 2. - - Living causes damage to cells → A network of molecular, cellular and physiological maintenance and repair systems creates a buffering capacity against such damages → Aging leads to progressive shrinkage of the buffering capacity, reduced stress tolerance and increased vulnerability. In the image below you can see what factors impact the immune system with age and what the results of those changes are:  Aging impacts: - - - - - - - - Consequences: - Schematic summary: