This article has lots of detail about markers of aging. I’m not up to date on many of them, but some I’ve discussed before. I’ve covered telomeres, autophagy. And my book, Radical Resilience had an entire chapter on Longevity Science and Anti-Aging.
López-Otín, Carlos et al.
Cell, Volume 186, Issue 2, 243 – 278
cell article on measures of aging (PDF at the link) a summary of the pdf follows the abstract
Aging is driven by hallmarks fulfilling the following three premises: (1) their age-associated manifestation, (2) the acceleration of aging by experimentally accentuating them, and (3) the opportunity to decelerate, stop, or reverse aging by therapeutic interventions on them. We propose the following twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected among each other, as well as to the recently proposed hallmarks of health, which include organizational features of spatial compartmentalization, maintenance of homeostasis, and adequate responses to stress.
Here’s a 300-word bullet-point summary of the Cell article “Hallmarks of Aging: An Expanding Universe”:
Summary of “Hallmarks of Aging: An Expanding Universe” (Cell, 2023)
- Definition of Hallmarks: Aging hallmarks must (1) appear with age, (2) accelerate aging if worsened, and (3) be reversible to delay aging through intervention.
- Updated List of Hallmarks (12 Total):
- Genomic instability – DNA damage accumulates over time due to environmental and internal factors.
- Telomere attrition – Shortening of chromosome ends leads to cell senescence.
- Epigenetic alterations – Changes in DNA methylation, histones, and chromatin structure affect gene expression and longevity.
- Loss of proteostasis – Impaired protein folding and clearance causes toxic buildup, seen in diseases like Alzheimer’s.
- Disabled macroautophagy – Reduced cellular cleanup of waste and damaged organelles contributes to aging.
- Deregulated nutrient sensing – Disruptions in pathways like insulin/IGF-1 and mTOR influence metabolism and lifespan.
- Mitochondrial dysfunction – Declining energy production and increased oxidative stress damage cells.
- Cellular senescence – Accumulation of non-dividing cells promotes inflammation and tissue dysfunction.
- Stem cell exhaustion – Diminished regenerative capacity leads to organ decline.
- Altered intercellular communication – Miscommunication between cells causes systemic aging effects.
- Chronic inflammation – “Inflammaging” underlies many age-related diseases.
- Dysbiosis – Age-associated gut microbiome changes impair health and immunity.
- Classification:
- Primary hallmarks cause initial damage.
- Antagonistic hallmarks are responses that can become harmful if excessive.
- Integrative hallmarks result from accumulated damage and drive aging symptoms.
- Therapeutic Targets: Many interventions (e.g., caloric restriction, senolytics, autophagy activators, telomerase activation) have shown promise in delaying aging and enhancing healthspan in animal models and early human trials.
- Conclusion: Aging is a complex, interconnected process; targeting any hallmark may positively impact others, opening doors for holistic anti-aging therapies.
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