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Get to grips with the 12 hallmarks of aging and what they each mean for your health. Here we explore what each of these unique hallmarks is and how they interact with each other to contribute to aging.
When we think of aging, it's often the negative aspects that spring to mind, gray hair, loss of cognitive function, and reduced mobility, but aging can also be a positive thing. From the moment we are born, we start to age which brings with it knowledge, coordination to enable us to walk, and cognitive enhancements that allow us to talk and interact with each other and the world around us. So, aging is a necessary part of the human life cycle.
The scientific definition of aging is “the time-related deterioration of the physiological functions necessary for survival and fertility.”[i] Although this helps to explain what it is, it doesn’t really answer the question of why we age and whether there’s anything we can do to help slow it down.
The simple answer to this is no one really knows why, but that doesn’t mean scientists haven’t tried to find out. Several theories try to explain why and how, including:
However, more recently scientists have made some breakthroughs in trying to understand the complex mechanisms that underpin aging by identifying 12 important and unique hallmarks that define aging.
The hallmarks of aging theory emerged from the need to understand the complex mechanisms that participate in the aging process.
Originally, López-Otín et al (2013) identified nine common hallmarks of aging in different organisms, particularly mammals in their paper entitled “The Hallmarks of Aging”[ii].
The paper outlined nine hallmarks and quickly became a popular discussion point amongst researchers and was frequently cited in papers. Yet, over the last 10 years, the science has evolved and in 2023 López-Otín and Co published an updated paper “Hallmarks of Aging: An Expanding Universe” which included 3 new hallmarks.
The 12 hallmarks identified in the paper are the original nine:
Plus, the three new hallmarks:
Each hallmark must meet three proposed criteria:
Figure 1. The 12 hallmarks of aging.These are the 12 hallmarks of aging proposed by, López-Otín et al (2013) which build on the nine hallmarks they identified in 2013. These 12 updated hallmarks are grouped into three categories: primary, antagonistic, and integrative.
Genomic instability means the build-up of DNA damage over time which can lead to mutations and abnormalities. These genetic changes cause disturbances in cellular function and contribute to the development of age-related diseases. For example, one disease that’s synonymous with aging is Alzheimer’s Disease, a neurodegenerative condition affecting around 6.7 million Americans over 65[iii]. Genomic instability, specifically the loss of DNA repair has been identified as a potential instigator of disease progression[iv].
Some research has investigated ways to slow down or protect cells from degeneration. SenGupta et al (2022) found that krill oil could promote the survival of dopaminergic neurons in Parkinson’s Disease, promoting a healthier aging pathway[v].
Telomeres are the protective ends of chromosomes, stopping them from fraying or becoming tangled[vi]. Naturally, telomeres shorten every time a cell divides, until they become so short that the cell can’t divide properly, entering a state of senescence and eventually dying.
This process of telomere shortening has long been associated with aging and disease development. For example, shortened telomeres have been linked with genomic instability and cancer development and elderly people are three to eight times more likely to die from heart-related and infectious diseases if they have shorter telomeres[vii].
Figure 2.Telomeres are the protective caps at the end of a chromosome, a structure present in the nucleus of cells that carry genetic information. Source: National Human Genome Research Centre.
Lifestyle improvements, such as regular physical activity and a healthy diet, can delay telomere shortening[viii]. Urolithin A has also been shown to delay cellular senescence, resist oxidative stress, and promote healthy aging.
Throughout our lifetime, our DNA can be changed chemically by varying lifestyle and environmental factors, affecting how the cells read and interpret genetic information. In turn, this can have a knock-on effect on how genetic products including proteins are expressed.
As we age, epigenetic changes can lead to several diseases because of abnormal gene expression, including cancer, neurological and memory disorders, and autoimmune conditions like rheumatoid arthritis[ix].
Proteostasis is the regulation of cellular proteins to maintain the health of the proteome and the organism. It ensures that the proteins are correctly folded, degraded, and synthesized. Many age-related conditions, such as Alzheimer’s and Parkinson’s Disease are linked to impaired protein homeostasis resulting from misfolded proteins, for example[x].
The balance in the proteome reduces with age which causes an accumulation of damaged or misfolded proteins. This is known as loss of proteostasis.
Macroautophagy is a cellular process whereby the cell can break down and recycle its contents for energy and metabolite production. The cell breaks down damaged components or proteins where they are engulfed by a structure called the autophagosome.
If macroautophagy is impaired or disabled, it can lead to the accumulation of damaged cell components which can cause disease[xi]. Diet can affect macroautophagy and the process may be upregulated by stimulating certain enzymes and proteins like AMPK and SIRT1 with dietary compounds such as berberine[xii]. At the same time, some foods may stimulate the production of natural compounds known to slow down aging and promote macroautophagy, such as urolithin A.
The body’s cells have nutrient-sensing pathways that help the body respond to the nutrients we take in from the food we eat, which regulates how our cells grow, store energy, and respond to stress. In effect, these pathways help to ensure that the nutrients we eat do not place too much stress on our bodies.
However, as we age these pathways may not work as well as they once did, increasing the risk of developing metabolic diseases like obesity and type 2 diabetes[xiii].
Mitochondria are known as the powerhouse of the cell because they generate most of the chemical energy needed for the biochemical reactions taking place in cells. When mitochondria function properly, they produce chemical energy, which is stored in molecules called adenosine triphosphate or ATP[xiv].
However, with increasing age, the oxidative capacity of the mitochondria declines. Research shows that our ATP-producing capacity reduces by 8% every 10 years and the elderly “have a 1.5 fold reduction in oxidative capacity per mitochondrial volume.”[xv] That means that mitochondrial efficiency declines which can lead to an increased production of reactive oxygen species (ROS), leading to oxidative stress, cell damage, and illness.
Regular exercise can benefit mitochondrial health by regulating mitochondrial respiration and improving ATP production and mitochondrial function[xvi].
When cells can no longer divide and multiply but are still alive and active it’s called cellular senescence. Multiple factors can spark cellular senescence, including:
With this in mind, it’s easy to see why the 12 hallmarks of aging are distinct but all interconnect to bring about aging. Cellular senescence is a natural part of getting older and has some benefits. For example, it stops damaged cells from multiplying, potentially causing even more damage like cancer. However, a build-up of senescent cells can also be harmful because they can release proteins that encourage inflammation, contributing to many age-related diseases (Figure 3).
Figure 3. The link between senescence and disease.Source: McHugh and Gil (2018)[xvii].
Mice studies have demonstrated that the removal of senescent cells can preserve cognitive function. Therefore, targeting these cells may have therapeutic benefits for preventing or delaying the onset of age-related illness[xviii].
Stem cells are cells that haven’t differentiated into a specific cell yet. For example, white blood cells would have begun as stem cells before changing into the specific white blood cell they are. Stem cells are essential for the maintenance and repair of the body’s tissues and organs.
Stem cell function and numbers reduce with age. That’s why it can take longer to heal from an injury as we get older[xix]. For example, a broken bone in a child may take 4 to 8 weeks to heal but it can take significantly longer in older adults.
Cells communicate with each other in various ways, just like we do as humans. But instead of talking, using hand gestures, or writing letters, cells interact through direct contact, using signalling molecules, or via electrical impulses[xx]. The constant communication pathway ensures the continued health and function of your organs.
However, as we age these communication pathways can become altered or disrupted which can cause inflammation, slow tissue repair, and the onset of chronic low-grade inflammation called inflammaging[xxi].
Inflammaging, or chronic inflammation in aging, is low-grade inflammation that is present when there is no infection in the body. It is a biomarker of accelerated aging and is a risk factor for many conditions, including:
This type of chronic inflammation is driven by increases in circulating pro-inflammatory molecules. It’s also associated with other hallmarks of aging such as genomic instability, disabled macroautophagy and loss of proteostasis. As the presence of inflammation increases, your body’s ability to deal with it declines as immune function reduces, leaving you susceptible to illness and infection.
The final hallmark of aging is dysbiosis or an imbalance in the composition and abundance of the gut microbiota, the natural ecosystem in the gut consisting of bacteria, viruses, and fungi. Simply, dysbiosis is where harmful microbes outnumber the beneficial ones[xxii].
Several factors contribute to dysbiosis, including:
Dysbiosis is also linked to various health conditions like inflammatory bowel disease, obesity, heart disease and depression. Although it can cause disease, dysbiosis can also be caused by disease. With age, dysbiosis can trigger a cascade of inflammatory events which may contribute to age-related conditions.
That’s why our MitiAging product targets the health and balance of your gut with 5 human milk oligosaccharides (HMOs) and 10 strains of probiotic bacteria, to help you restore balance, as well as the Urolithin A precursor, ellagic acid, known to restore and rejuvenate the mitochondria.
Aging is a complex process that’s underpinned by 12 unique but interconnecting hallmarks. By understanding these hallmarks, we can build a greater knowledge of why humans age and what we can do to help delay or even reverse it.
Supplements like the MitiAging bundle can target some of the key areas that contribute to aging, such as the mitochondria and the gut, giving you a head start in taking control of your aging process.
Written by: Leanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome.
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