Targeting Aging

In 2018, the World Health Organisation added extension code, XT9T, for ageing-related disease to the International Classification of Diseases (ICD). In 2019, the 11th revision of the ICD reclassified XT9T from ageing-related disease to disease caused by ageing [32251691]. This formally affirmed what had been known for decades in scientific research circles: that ageing is the greatest risk factor for many chronic and debilitating diseases [22975005]. Moreover, by understanding and targeting the processes of ageing, we will have the greatest opportunities for preventing age-related chronic disease and extending lifespan.


What is aging?

Aging manifests as an increase of chronic disease and decrease in physical resilience. Notable aging traits include chronic inflammation, fibrosis, slowed or incomplete wound repair, sarcopenia, bone loss and metabolic dysregulation. The mechanisms underlying aging traits include stem cell dysfunction, cellular senescence, mitochondrial dysfunction, reduced DNA repair and gene expression dysregulation. There is also an accumulation of  increased reactive oxygen species (ROS), misfolded proteins and glycated molecules. 

The mechanisms associated with aging traits are interlinked. For example, cellular senescence leads to inflammation, fibrosis and DNA damage. This interlinking may be exploited to investigate interventions that target multiple mechanisms.   


How is anti-aging being pursued?

Research is continuously uncovering the molecular mechanisms associated with aging and their respective connections to physiology and disease. Genentech (Roche subsidiary and developer of the first synthetic human insulin) is actively researching cellular reprogramming to safely rejuvenate organs in model organisms. Calico Life Sciences, a Google subsidiary, is focused on mapping the processes of aging and age-related disease. Altos Labs, a new biotechnology firm whose investors include Jeff Bezos and Yuri Milner, and headed by a some of the most prominent names in aging research, has a stated mission of transforming medicine through cellular rejuvenation. 

The American Federation for Aging Research is presently seeking Federal Drug Administration (FDA) approval for the drug Metformin (a commonly prescribed type 2 diabetes medication) to be classified as an intervention for aging (indication). Numerous clinical trials are registered where the condition being investigated is actually listed as aging rather that aging-related disease and the interventions involve targeting some of the mechanisms of aging. 


Is anti-aging possible?

Much like an old car undergoing increasing mechanical breakdown, the aging process has long been considered to be a gradual culmination of numerous random molecular changes resulting in the functional deterioration of tissues and organs.

The discovery of an epigenetic clock demonstrated that aging is not characterised by random damage but appears to follow a time-based sequence of epigenetic events that predict chronological age that may be modified by the environment. It’s been shown that by using a combination of commonly prescribed drugs, the the epigenetic clock can be ‘rewound’ by 1-2 years in humans. 

That senescent cells are not only the byproduct but actual driver of aging led to evidence that removal of such cells delayed some aging phenotypes. Presently there are numerous human trials of senolytic compounds to treat aging related disease. Indeed the most well researched intervention for lifespan extension, caloric restriction, appears to mediate its longevity effects by increasing the removal of senescent cells. 

Autophagy, the removal of damaged or low functioning intracellular components including mitochondria, is also increased by caloric restriction and is a target for numerous existing and new interventions under investigation. Using techniques developed for stem cell manipulation, aging has been reversed in tissues of laboratory animals. The evidence from numerous lines of clinical and animal research point to dramatic leaps in the next decade towards our understanding and modification of the aging process. 

Today, using the epigenetic clock as a guide, and with interventions that target senescent cells and autophagy, we can delay aging with an accompanying increase in healthy lifespan.  


Aging as missing biomarker   

Despite these advances, with the exception of a few progressive physicians, the medical community largely ignores the variable of biological aging as a direct contributor to disease. With mainstream medicine focused on disease-specific medicine rather than considering the mechanisms and biomarkers of aging as drivers and signals of disease, a large swathe of diagnosis, prognosis and treatment options are ignored. 

In apparently healthy patients, aging may be already laying the molecular groundwork for disease well before the clinical phenotype is detectable and may explain how otherwise healthy middle-aged individuals appear to be suddenly stricken by disease.

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