Hallmarks of Aging
Our metabolism tanks and aging acceleratES around 60
As we age, several factors conspire to reduce our energy expenditure and alter our metabolism so that the incidence of chronic diseases starts growing dramatically around the time we reach 60 years of age -- see the figure.
Interestingly, throughout adulthood until that age metabolism stays constant after peaking in early youth.
Research shows that some individuals, however, manage to maintain a youthful metabolism profile and active lifestyles into their late 80ties. While achieving this may seem like a serious challenge, since these individuals tend to be quite athletic, with the help of the right supplements that address the hallmarks of aging, this becomes within the reach of everyone.
Hallmarks of Aging (HoA)
About a decade ago longevity science identified 10 fundamental factors as to why and how people age, called hallmarks of aging (see the diagram). This is significant, because a myriad of manifestations of aging and numerous age-related diseases can now be mostly explained by a small number of causes. This suggests that targeting 10 classical hallmarks of aging may fundamentally alleviate older age conditions. The intracellular hallmarks include: (1) genomic instability, (2) telomere attrition, (3) epigenetic alterations, (4) loss of proteostasis, (5) deregulated nutrient-sensing, (6) mitochondrial dysfunction, (7) cellular senescence, (8) stem cell exhaustion, and (9) altered intercellular communication were proposed by López-Otín and colleagues in 2013. The extracellular factor (10), matrix stiffening, was proposed by de Grey even earlier. For the latest update on the aging hallmarks see below.
While 10 is still a sizeable number of factors to address, a slew of clinical trials during the last decade uncovered multiple molecules, mostly derived from foods and plants, that can actually address multiple hallmarks simultaneously. These substances have proven to be helpful in delivering health improvements to people in their 50ties and beyond.
An update on hallmarks of aging
New hallmarks of aging were proposed at the 2022 Copenhagen meeting on aging -- see the diagram.
Summary
The hallmarks of ageing framework has been instrumental in guiding the research on the biology that affects our aging. The last 10 years of intensive research has enabled the ageing research community to pinpoint the hallmarks of aging, which includes malfunctioning autophagy, microbiome disturbances, changes in mechanical properties and genes that are not splicing correctly. By looking at both the old and new hallmarks of ageing in a whole new way, we might be able to better understand the process of managing age-related disease and lead to more fulfilling, happy and healthy lives.
New hallmarks of senescence
Compromised autophagy is observed in ageing conditions such as neurodegeneration and aging of the immune system. Increase in autophagy can extend mouse lifespan, and improve immune system in elderly people.
Dysregulation of RNA processing has been observed in ageing people and targeting it can improve their condition in part by restoring youthful patterns of splicing factor expression. Similarly, alternative polyadenylation of mRNAs, already known to contribute to cancer is altered with ageing and may contribute to senescence.
Microbiome disturbances: recently notable changes in the gut microbiome with age have been identified, pointing in particular to changes in gut bacterial composition such as loss of diversity. This shift in microbial populations can add to inflammation in aging populations.
Altered mechanical properties applies both to the intracellular and to the extracellular space. For example, in aging fibroblasts actin that can be readily polymerized and depolymerized during cell motility, gradually changes into stable stress fibers of actin. This can obstruct movement of immune system cells, which in turn can cause significant tissue damage on migration to sites of inflammatory signaling. The skeleton of the nucleus is also altered during ageing and can result in extrusion of chromatin into the cytoplasm, which triggers the release of inflammatory messengers (SASPs).
Extracellular matrix also changes with ageing: Increased rigidity and loss of elasticity, arising through glycation cross-links between collagen molecules, can lead to multiple age-related disease states such as hypertension
Inflammation: Inflammageing, age-dependent chronic inflammation, is implicated in a wide range of age-related diseases. Originally inflammation was considered part of the hallmark 'altered intercellular communication', however its large contribution to the ageing process merits it as a separate hallmark of ageing.
Based on: New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging, Vol. 14, Issue 16 pp 6829—6839
