The Basics of Senescence and Autophagy: Two Key Regulators of Aging

Although they are two different processes, senescence and autophagy both play an essential role in how quickly—or slowly—our cells age. High levels of cellular senescence and impaired autophagy can lead to degenerative processes like DNA damage, cellular stress and inflammation, which cause aging and age-related conditions. 

But what exactly are cellular senescence and autophagy? Let’s take a closer look at what these cellular processes are—and how to make them work better to support healthy aging and longevity. 

Cellular Senescence: How Zombie Cells Cause Aging

Simply put, senescence is when cells stop dividing and lose their function. This irreversible growth arrest commonly occurs with older age or in response to stressors like inflammation or oxidative stress—the accumulation of reactive oxygen species that damage cells and DNA.

However, while these senescent cells lose function, they don’t die. Instead of undergoing the routine and programmed cell death called apoptosis, senescent cells enter a “zombie-like,” half-alive state that damages neighboring tissues and cells. This damage occurs through the senescence-associated secretory phenotype (SASP), which secretes a cascade of destructive and inflammatory compounds. 

The number of senescent cells that secrete SASP compounds increases with age in many vital tissues, including the brain, lungs, kidneys, heart and blood vessels. Therefore, a buildup of senescent cells and their subsequent inflammatory cascade contributes to age-related conditions in these organs and tissues. 

Another factor that plays a role in cells becoming senescent is telomere length. Telomeres can be imagined as the plastic casing protecting the tip of a shoelace, as these repetitive strands of DNA “cap” the ends of our chromosomes. These endcaps protect the critical genetic information inside the chromosome from damage and dysfunction. 

Telomeres and cellular senescence go relatively hand in hand, as telomeres shorten with each cell division. When a cell reaches the end of its telomere, it can no longer replicate and is considered senescent.

Autophagy: Our Cellular Housekeeping System

Another fundamental cellular process for longevity is autophagy. Meaning “self-eating” in Greek, autophagy is a quality control mechanism that removes unnecessary, toxic or dysfunctional cells or cell parts.

People with low autophagic capacities are more likely to have accelerated aging or develop age-related conditions. Autophagy is commonly referred to as our bodies' housekeeping or recycling systems, allowing for the orderly degradation and removal of cellular components to maintain functionality. 

Disruptions in the autophagy process lead to a buildup of dysfunctional and damaged cells in the body. Conversely, studies show that upregulating autophagy in animals leads to lifespan extension. 

Targeting Senescence and Autophagy to Slow Aging

Researchers have started testing and implementing senolytics—drugs or chemicals that remove senescent cells from the body. However, these compounds tend not to have specific targets, leading to accidental clearance of non-senescent cells and increasing the risk of toxic side effects. One commonly used senolytic is a combination referred to as DQ—dasatinib plus quercetin. While quercetin is a natural compound found in fruits and vegetables, dasatinib is a chemotherapy drug that can cause undesirable side effects.

Other compounds studied for their role in reducing or clearing senescent cells include pterostilbene, fisetin and berberine. The benefits of using natural plant-based compounds like these are wide-reaching, including their ability to selectively kill off senescent cells without causing toxic harm to normal, proliferating cells.

One study also found that NMN (nicotinamide mononucleotide), a precursor to the vital coenzyme NAD+, fights cellular senescence in the retinal cells of the eye, while another showed that NMN reduced senescent alveolar cells in the lungs.

When it comes to autophagy, researchers have identified several ways to boost this internal housekeeping, including resveratrol, curcumin, green tea extract, exercise, intermittent fasting or caloric restriction and getting enough deep restorative sleep. 

Overall, strategies to support both healthy autophagic activity and clearance of senescent cells are two vital ways to promote healthy aging and longevity. 

References: 

Fang T, Yang J, Liu L, Xiao H, Wei X. Nicotinamide mononucleotide ameliorates senescence in alveolar epithelial cells. MedComm (2020). 2021;2(2):279-287. Published 2021 May 27. doi:10.1002/mco2.62

Kou X, Chen N. Resveratrol as a Natural Autophagy Regulator. Nutrients. 2017;9(9):927. doi:10.3390/nu9090927

Li FH, Li T, Ai JY, et al. Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model. Front Physiol. 2018;9:571. doi:10.3389/fphys.2018.00571

McHugh D, Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues. J Cell Biol. 2018;217(1):65-77. doi:10.1083/jcb.201708092

Nakamura S, Yoshimori T. Autophagy and Longevity. Mol Cells. 2018;41(1):65-72. doi:10.14348/molcells.2018.2333

Ren C, Hu C, Wu Y, et al. Nicotinamide Mononucleotide Ameliorates Cellular Senescence and Inflammation Caused by Sodium Iodate in RPE. Oxid Med Cell Longev. 2022;2022:5961123. Published 2022 Jul 18. doi:10.1155/2022/5961123