Globally, people pour approximately €60 billion annually into treatments aimed at combating the effects of ageing, such as Botox, hair colouring, and creams. Even though these remedies create an appearance of youth, they are unable to fully arrest the progression of time.
In quest for a more effective solution, scientists are exploring the biological triggers of ageing. Their objective is to present methods to either pause the visible indicators of growing old, or more notably, to inhibit age-associated ailments. This process is frequently identified as ‘the hallmarks of ageing’.
Many of the hallmarks fall under two wide-ranging classes – regular damage at the cell level, and the body’s diminishing efficiency in discarding old or malfunctioning cells and proteins.
“The key point about the hallmarks is that, those are the issues that present themselves as we age, and reversing them could lead to healthier or longer life,” remarked Prof Linda Partridge, a leading research figure from the University College London’s biosciences division, who assisted in creating the ageing hallmarks model.
At this moment, most of this investigative work has been implemented on animals, nevertheless, scientists are progressively incorporating human beings into this research. Recognising the how and why of ageing can help us better understand the regular updates on the latest ‘revolutionary’ breakthroughs, observed Venki Ramakrishnan, a Nobel laureate and biochemist who’s penned a new publication on this topic titled ‘Why We Die: The New Science of Aging and the Quest for Immortality’.
Experts discussed the hallmarks of ageing, their role in disease manifestation and the different ways researchers are trying to amend them. Two principal concepts fought with ageing – degradation and disposal complications – have been illustrated below.
Degradation
A number of transformations related to ageing commence within our cells and genes, which start behaving unusually as we age.
DNA
Despite the common belief that our genes are constant from birth, DNA experiences modifications over time. Typically, mistakes appear when cells divide; these are random faults that surface when DNA gets replicated and transferred from one cell to another. Mutations could also stem from external influences such as ultraviolet light exposure from the sun.
While our cells have mechanisms to mend genetic mutations, their efficacy diminishes as we grow older. This challenges scientists as the reasons behind the decline of our DNA’s capacity to self-heal with age are still unclear. Andrew Dillin, a professor specialising in molecular and cell biology at the University of California detaches himself from certainty by labelling it a “$1 billion question”. It is known only that effectiveness reduces as we age, leading to cellular malfunction and, in extreme cases, triggering cancer due to mutations in genes that typically suppress tumour emergence.
Every duplication of a cell, inclusive of its DNA, results in ever-so-slight reductions in the length of the chromosome ends known as telomeres. These crucial parts of the genome are frequently compared to the plastic tips on shoelaces which safeguard against fraying. The cessation of cell division when telomeres have shortened too much is typically beneficial in our youth, assisting in the prevention of perpetual cell replication and potential cancer development. However, this telomere shortening emerges as a prominent issue in the ageing process, particularly affecting stem cells utilised in the renewal of skin, blood and other tissues.
Stem cells have their defence against this, though eventually, their telomeres are lost. Professor Dillin confirms that this leads to a depletion in stem cell populations. This reduction severely contributes to the visible signs of ageing such as grey hair and skin becoming progressively thin and less pliable. Products exist claiming to restore stem cells, however, there is scant evidence supporting these assertions.
Amendments to our genome brought about by epigenetics – chemical modifications that trigger the activation or deactivation of genes within a cell – occur as a consequence of our development and environment. Epigenetic changes can potentially depict an individual’s ‘biological age’. As per scientific finding, many epigenetic processes that modulate the behaviour and classification of our cells begin to deteriorate with ageing. If this materialises in large numbers of cells, it could detrimentally impact organ health and performance. For instance, epigenetic alternations in heart cells could lead to arterial thickening or a diminished capacity for the heart to respond favourably to exercise.
Dr Eric Verdin, current president of the Buck Institute for Research on Aging, has underscored the importance of ongoing investigations into ageing prevention focusing on reversible epigenetic modifications rather than DNA mutations.
Mitochondria are vital for cell health as they are the primary producers of energy within a cell. Their efficacy diminishes as we age, reducing their energy production and efficiency. Dr Verdin, who also works with companies developing longevity drugs, pointed out that deficiencies in energy generation can disrupt other cell functions.
Professor Dillin emphasised that cellular energy alterations impact other components of cellular wellbeing, including epigenetics. Furthermore, damaged mitochondria can escape cells and instigate inflammation, a hallmark of ageing linked to a myriad of persistent health issues. One suggested solution for improved mitochondrial health is consistent physical activity.
However, the ageing process also leads to the accumulation of defective cells due to damage mentioned earlier, along with a decrease in the body’s effectiveness in eliminating them.
Decayed cells are usually put into a state called senescence; they cease to multiply and begin to produce inflammatory chemicals, signalling the immune system for elimination. Despite this being an integral part of routine cell recycling, ageing leads to an expanded group of cells ready for disposal and a deteriorating disposal system, resulting in an increase in senescent cells that enhance inflammation levels.
In efforts to improve the removal of these senescent cells, scientists are examining the potential of a drug category known as senolytics, while the research remains at early stages.
Another challenge faced by the body in ageing is the removal of defective proteins. Comparable to DNA being the blueprint and cells acting as builders, essential proteins can be likened to the raw materials used in construction.
Proteins frequently become malformed, a condition often referred to as misfolded proteins. The body has various methods to correct these issues, however, as we grow older, these processes start to reduce their efficiency, leading to a buildup of misfolded proteins, causing health problems. A prominent medical condition connected to these unhealthy proteins is Alzheimer’s disease, where the accumulation of amyloid and tau form blockages and tangled messes in the neural pathways.
To get rid of these misshapen proteins and other dysfunctional cell components, the body utilises a mechanism known as autophagy, a Greek term meaning “self-consuming”. This process eradicates all defective components within the cell,” explained Dr Ramakrishnan. “Furthermore, if this process is interrupted, it results in the accumulation of, essentially, cellular waste, which can cause stress and accelerate the ageing process.”
The occurrence of autophagy decreases as we age. Certain medications, like rapamycin, that are currently being explored for their impact on ageing, have been shown to catalyse this process. Nonetheless, rapamycin can inhibit immune response in high concentrations and is primarily employed to avert organ transplant rejection. Therefore, some scientists have voiced concerns over healthy individuals consuming this drug.
Whilst anti-ageing treatments are still in the experimental stages and not yet ready for expansive usage, the experts remain hopeful about the future progression of this scientific domain. “Hitherto, advancements haven’t been exceptionally fast, but we expect significant breakthroughs,” Dr Partridge stated.
Currently, Dr Partridge advised that the most effective approach to promote healthy ageing is to maintain a healthy lifestyle comprising regular physical activity and balanced nutrition. This article was originally published in the New York Times.