Measuring the hallmarks of ageing – how can you track the underlying causes of ageing?
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Our body is not just a mundane structure; it's a thriving bio-city! Inside, there are trillions of tiny communities that treat the body as their whole world. These microscopic neighbours play roles in digestion, defence, and even influence our mood.
Collectively known as "omes," meaning whole, they maintain a delicate balance. Disrupting this equilibrium can send our inner world into chaos.
In this blog, let's delve into understanding some of the significant “omes” residing within us (in alphabetical order).
Starting with the brain, this ome controls every thought, memory, and action. The connectome is like a detailed map of neural connections in the brain. Studying this map helps us understand the language of the brain.
It operates on different levels. Some connections are clustered in hubs for quick communication in complex thinking. These hub areas include regions like the prefrontal cortex for decision-making and the hippocampus for memory.
Over time, some pathways in this ome become congested, slowing down information flow and affecting memory and processing speed. Other paths fade away indicating cognitive decline. Studies on the connectome in conditions like Alzheimer's reveal a deterioration of these neural connections, contributing to memory loss [1].
The human body goes beyond muscles and bones; it operates through electrical charges known as the "electrome." This ome encompasses all electrical activity within cells, tissues, and organs to carry out different processes.
The electrome is essentially a complex electrical network. Ion channels regulate the flow of charged atoms (ions) and create electrochemical gradients. These gradients act as a language for the electrome, controlling how cells communicate with each other, how organs work, and overall well-being.
Each organ has its own unique electrical patterns, like the heart's beats or nerve signals. As we age, this electrical system can get disrupted, leading to issues like arrhythmias, impaired nerve function, and slower wound healing [2].
The epigenome is a layer of chemical modifications that sits on top of the DNA, like instructions on how to read the genetic code. It doesn't change the actual DNA sequence, but it tells the cells which genes to turn on and off, influencing everything from your eye colour to your risk of disease.
For example, early childhood trauma can leave an epigenetic mark that increases the risk of mental health problems later in life. With each passing year, our epigenome accumulates "time signatures" – modifications that reflect the passage of time and the experiences we've had [3].
Genes that should be active get silenced, and vice versa. Specific gene promoters get over-methylated, shutting down genes. Histone modifications alter gene access. These changes lead to cell dysfunction, energy decline, chronic inflammation, and even cancer.
This ome refers to the sum total of our lifelong exposures. It includes the air we breathe, the food we eat, the pollutants we encounter, the social interactions we experience.
Early life exposures, from prenatal nutrition to childhood pollutants, lay down the foundation for future vulnerability or resilience to diseases. Air pollution can accelerate cellular senescence, while a healthy diet rich in antioxidants can bolster protective mechanisms.
The exposome isn't static; stress, sun exposure, and even the microbiome dynamics contribute layers throughout life. The lifelong environmental footprint silently accumulates with age, potentially shaping an unhealthy future. It may potentially lead to chronic inflammation, DNA damage, and premature ageing [4].
Genome is like a complete instruction manual for building and operating a living organism - the entirety of an organism's genetic information. This information resides in long, twisting molecules called DNA, packaged within thread-like structures known as chromosomes. Humans have 23 pairs of chromosomes, with one set inherited from each parent.
The genome dictates everything from the colour of the eyes to susceptibility to certain diseases. It's the reason why one might resemble their parents or siblings, yet possess unique traits.
While the genome remains largely constant throughout life, changes in epigenome alter the body’s ability to read the genetic code. This contributes to signs of ageing and leads to several diseases. From head to toe, an altered genome activity can sow the seeds of diverse diseases [5].
The gerontome is a collection of genes and molecular pathways associated with ageing. It is influenced by the environment, lifestyle, and cell events. It includes markers such as epigenetic changes, protein modifications, and DNA damage. The changes are shaped by factors like diet, exercise, and stress.
The gerontome is like an internal clock that ticks differently for each person. Unlike the fixed genetic sequence, the gerontome is flexible and affected by lifestyle choices. Each cigarette puff, sugar rush, and sleepless night leaves its mark influencing how we age. Gerontome’s unique composition explains why some gracefully traverse the years while others succumb to age-related ailments sooner [6].
The glycome refers to the entirety of sugar molecules (glycans) attached to proteins and lipids in our cells. These glycans serve as a complex language coordinating essential cellular functions. Individual glycans convey instructions, directing proteins, mediating cell-to-cell communication, and regulating immune responses.
As we age, the glycome undergoes notable changes. Simple, unbranched glycans increase, while complex ones decline. This alteration disrupts cellular communication, leading to issues like protein misfolding, weakened immunity, and impaired cell signalling. This glycan transformation is associated with age-related diseases, such as Alzheimer's, where protein aggregates impact brain tissue [7].
The ionome is the collection of essential and non-essential minerals, like sodium, potassium, and calcium, revealing their precise location and abundance. It is a part of numerous biological processes, from nerve impulses to bone formation.
The ion sodium facilitates nerve signals, while calcium coordinates muscle contractions. Any imbalance in the ionome can have profound consequences. For example, magnesium deficiency disrupts heart rhythm, while iron overload damages vital organs.
The ionome is not static; it evolves with environmental factors, diet, and, crucially, the passage of time. Calcium tends to accumulate in bones, while potassium levels may decline in muscle. These age-related variations can contribute to diseases like osteoporosis and muscle weakness [8].
The inflammasome is a complex of proteins acting as the body's first responders to danger. Sensing threats like infections or cellular debris, it triggers inflammation, a critical defence mechanism. This "guardian" unleashes potent inflammatory molecules to recruit immune cells and eliminate threats, even employing a controlled cell death called pyroptosis to prevent further damage.
While essential for protection, the inflammasome's actions can backfire with age. Chronic inflammation and cellular damage, hallmarks of ageing, can lead to overactive inflammasomes. This excessive inflammation fuels age-related diseases like Alzheimer's and autoimmunity [9].
The lipidome is the entire collection of fats and similar molecules in a cell. These diverse chemicals constantly shift, creating the dynamic landscape of life. Examples include cholesterol, which builds cell membranes, and fatty acids, important for energy storage and communication.
This complex lipid collection serves essential functions. Cell membranes, composed of specific lipids, regulate what enters and exits, maintaining cellular life. Lipids also fuel bodies, delivering energy reserves. Further, they act as messengers in crucial processes like inflammation and gene expression.
As we age, this carefully woven lipid structure starts to change. Cholesterol metabolism shifts, and the composition of cell membranes is altered. The balance of signalling lipids can also become disrupted, contributing to age-related diseases [10].
The metabolome is a collection of thousands of small molecules with weights less than 1500 Daltons. From sugars fueling our cells to amino acids building proteins, they maintain overall cellular processes.
Examples include glucose, the energy currency; cholesterol, a vital membrane component; and antioxidants, defenders against cellular damage. These molecules constantly churn, interacting, and transforming - reflecting our diet, environment, and even emotions.
As we age, changes occur in the metabolome, contributing to conditions like diabetes and Alzheimer's. Studying the metabolome helps us understand these shifts. By analysing blood, urine, or tissue samples, we can identify telltale metabolites associated with specific diseases. This holds immense promise for early diagnosis and personalised medicine [11].
Beyond our own 23,000 genes lies a hidden ome: the metagenome. This vast collection of genetic material comes not from us, but from the trillions of microbes residing within our bodies. Bacteria, archaea, fungi – these tiny inhabitants contribute millions of additional genes, forming a unique ecosystem vital to our health.
Our gut microbiome, for example, harbours a metagenome with ten times the genes of our own genome. These microbial genes code for functions we lack, aiding digestion, producing vitamins, and protecting against pathogens. They influence immunity, metabolism, and even brain function.
Certain beneficial bacteria decline with age, replaced by opportunistic and potentially harmful organisms. This creates a less diverse and functionally less efficient ecosystem, contributing to diseases [12].
The methylome, part of the epigenome, are like chemical tags on the DNA, distinct from the genetic code itself. These tags, called methyl groups, act like molecular switches, attaching to specific sites on the DNA molecule. Like tiny on/off buttons, they can silence genes, preventing their expression, or leave them accessible for transcription into proteins.
This layer of epigenetic control plays a crucial role in our biology, influencing development, cell function, and overall health. For instance, in females, one X chromosome is randomly inactivated by methylation, ensuring proper dosage balance.
Global levels of methyl groups decrease as we get older, potentially disrupting gene regulation and cellular function. Methylation patterns may also alter at specific genes, often associated with cancer, neurodegeneration, and cardiovascular disease [13].
The human microbiome is a vast hidden world of trillions of tiny organisms - bacteria, fungi, and viruses - inhabiting our skin, gut, and other body surfaces. These diverse communities, like miniature ecosystems, play a crucial role in our health. It’s important to note that the microbiome includes all the living organisms, while the metagenome refers to all of the organism's genetic information.
Microbiome undergoes significant changes with time. The younger microbiome is more adaptable and can bounce back from environmental disturbances like antibiotic use or dietary changes. With age, this resilience might decline, making individuals more susceptible to microbiome imbalances and associated health conditions [14].
This ome is the interplay between one’s unique genetic makeup and how their body responds to specific nutrients. It's not just about genes dictating what we eat; it's a two-way street. Certain gene variants influence how efficiently we absorb and utilise various nutrients, impacting metabolism, health risks, and even longevity.
For instance, a common variant in the FTO gene may predispose to obesity. Another gene variant influences vitamin D metabolism, potentially altering bone health.
Gene expression shifts with age, and epigenetic modifications, like chemical switches on DNA, can alter how nutrients interact with our genes. This can explain why dietary needs evolve with time. Some may find their cholesterol rises with age, while others develop lactose intolerance [15].
The oculome refers to the collective spectrum of genes and molecular pathways driving eye development and function. This ome guides everything from how our eyes form in the womb to how they process light and adjust to focus. Crucially, the oculome also dictates how our vision ages, making it a captivating lens into the biology of ageing.
Examples of oculome components include genes like PAX6, essential for embryonic eye development, and crystallins, proteins forming the lens. These elements influence everything from tear production to retinal degeneration.
Over time, mutations accumulate, protein aggregates form, and cellular repair mechanisms weaken in the eye. This manifests as common age-related vision problems like cataracts, glaucoma, and macular degeneration [16].
The proteome is not a singular entity, but an assembly of millions of proteins. These are the workhorses of our cells, each with a unique fold, shape and function, constantly interacting and adapting to maintain our health.
From enzymes that catalyse essential reactions to structural proteins that build our tissues, the proteome coordinates the functions of our cells. Think of insulin, the protein key unlocking glucose for energy, or antibodies, the vigilant guards recognising and neutralising foreign invaders.
The rate of protein production slows with age, some folds and structures become distorted, and others accumulate in unwanted clumps. These alterations contribute to the decline in cellular function and resilience characteristic of ageing. This may lead to age related pathologies like metabolic diseases or even cancer [17].
The transcriptome is a dynamic collection of RNA molecules. This ome mirrors the ongoing activities within a cell. It constantly shifts, reflecting which genes are actively being read and translated into proteins.
This "language" of RNA shapes everything from energy production to development and response to the environment. Techniques like RNA sequencing provide snapshots of the transcriptome, exposing the unique expression patterns of healthy and diseased cells, or cells at different stages of development. A decrease in transcriptome activity with age contributes to various metabolic disorders, cardiovascular diseases, and may even play a role in the development of cancer [18].
This vast viral ecosystem, known as the virome, constantly interacts with our biology, playing a complex and dynamic role in health and ageing. Unlike the well-known "pathogenic" viruses that cause illness, many members of our virome are commensal, residing peacefully alongside cells. Others, called latent viruses, remain dormant within our genome, their activity potentially triggered by future circumstances.
Examples of these viral residents include bacteriophages, which target and eliminate harmful bacteria, contributing to gut health. Certain viruses even influence our gene expression, impacting immune function and metabolism.
The diversity of commensal viruses often declines with age, potentially impacting their beneficial effects. Latent viruses may be reactivated by age-related immune decline, contributing to age-associated diseases [19].
Beyond what meets the eye, our body emits a unique scent, the volitome. It is a unique blend of volatile organic compounds (VOCs) wafting from the cells, tissues, and microbiome.
The VOCs composing this fragrant signature are diverse, ranging from simple hydrocarbons to complex sulfur-containing molecules. Each breath, sigh, and even whisper releases these compounds. This provides valuable clues about our wellbeing, with specific VOCs linked to stress, illness, and even the early stages of disease.
As we age, the scent subtly shifts. The vibrant notes of youth, enriched with floral and citrusy tones, gradually give way to a deeper, muskier aroma. Monitoring the subtle shifts in the volitome's harmony could one day become a non-invasive tool for early disease detection and personalised health monitoring [20].
The decisions we make in our daily lives have a profound impact on our internal world. Whether it's the food we eat, the way we move, or the connections we form, each plays a role in shaping the narrative of our omes. Opting for a nutritious diet, staying physically active, and surrounding ourselves with positive influences collectively contribute to happy and healthy omes. Concurrently, scientists are actively investigating strategies to uphold the integrity of our omes as we age.
Blog written by Sanjana Gajbhiye.
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