What is Cellular Housekeeping and what does it have to do with Aging?

Housekeeping, can mean a myriad of things such as keeping your house in good working order, keeping it clean and tidy, the preparation of food to feed the participants and repair and maintaining its components so that the house does its job of keeping us clean, warm and nourishing its constituents. It’s an active process that requires time, energy, thinking, raw materials and skills. When we neglect to keep up with our housekeeping our house very quickly can fall into disrepair.


It's probably no surprise that our cells need to also attend to keeping their house. A cell needs to be free of waste, repair broken components, generally maintain, nourish, and look after itself. Our cells are self-repairing houses with tiny self-repairing nanomachine residents that all play their role to keep the cell working efficiently and effectively. For this reason, cellular housekeeping is an active process that is designed to identify those cells and cell components that are becoming broken or inefficient and remove, recycle and replace them with new more vital cells. And when these housekeeping processes decline, as happens when we age, it turns out to have quite significant negative effects on our cells and our overall health.


Autophagy – the fine art of cellular housekeeping


A big part of our cellular housekeeping is a process known as autophagy, so named because its Latin origins, auto- meaning self and -phagy meaning to eat. Autophagy is triggered when a cell is past its best used by date, when it stops dividing because something has gone wrong or because a component of the cell is damaged and needs to be removed and replaced.


As we age three key components of the housekeeping process become compromised which contribute to the development of many of the health conditions we accumulate as we age. The first of these is something called cellular senescence. This describes a state where the cell sits in limbo having completed its useful tour of duty in the body or has been damaged in the line of duty and is waiting to be removed. Senescent cells secrete cytokines, chemical messengers that cause inflammation. They do this to attract our immune system whose role is to clear them out and recycle their components. As it often turns out to be the case, when we are young this process works efficiently, and senescent cells are identified and removed as and when they appear.


However, recently we have learnt that this process becomes less efficient as we age and over time, we accumulate a burden of senescent cells that are all secreting inflammatory chemicals in an attempt to be picked up and removed by the immune system. Just like a noisy neighbor who pollutes our soundwaves and makes living next to them unpleasant, having a senescent cell as a neighbour affects all of the cells around it. This process is part of what drives inflammaging, the increasing levels of inflammation in our bodies as we age. At best it causes a few aches and pains and worst it drives disease and accelerates the breakdown of cells and organ function as we get older.


Nutrient sensing – how our cells know what to do with our food


Another housekeeping component is something called nutrient sensing. Our bodies are in a constant state of flux as we wear out and replace the cells in our body. Some cells like our skin cells have a short life cycle whereas our neurons are typically with us for life and rely on other cells to help them repair and maintain themselves. In our early years our body is in a continuous process of growth with periods of recycling and renewal but as we reach adulthood we slip into a cycle of renewal and removal that is balanced towards the status quo rather than growth. This cycle is often driven by the nutrients we have available to us. When we eat, a cellular nutrient sensor called mTOR turns on and our body moves into growth mode. When we are hungry our bodies flip that switch into removal and recycling mode ready so that when we eat again our body rebuilds new fresh fully functioning cells. This process triggers autophagy and generally keeps our bodies in optimal working order. Unsurprisingly, our nutrient sensing processes also decline as we age and when we combine it with the always on Western diet and an over abundance of food then we have a recipe for disaster because our body gets stuck in growth mode without periods of cell removal and recycling meaning we don’t have the chance to clear out cells that are damaged and they build up. This has a significant impact on our overall health and longevity.


Proteostasis – keeping our cellular machinery functioning optimally


The final element of housekeeping that is important is a process called proteostasis. Proteostasis describes the process of keeping our proteins in good working order. Most of us associate protein with muscle but that’s just a small part of what proteins do in our body. They are essential and complex molecules that facilitate many of the activities that occur in our cells. Just like all components of our cells break and need to be repaired proteins are constantly made, broken down, recycled, and refreshed so that they function optimally. Proteostasis declines as we age, and broken proteins can build up inside our cells causing significant health issues. A good example of this is Alzheimer’s Disease where proteins build up in our brain cells and interfere with brain function. Autophagy is a key process as part of keeping our proteins in good working in order.


Autophagy is king


It turns out stimulating autophagy is very important for our health as the process removes senescent cells and dysfunctional proteins. We are learning how important it is at just the right time because we are at a time in human history where many in the developed world have an abundance of food and nutrition. How to stimulate autophagy? Having periods where we are hungry is a great start and is why we get the health benefits from occasionally fasting. Exercise is great as it stimulates the breakdown and rebuilding of tissue. Taking supplements and medicines that inhibit mTOR is also a promising strategy and is an active area of research to establish the exact health and longevity benefits associated with modulating mTOR activity.