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Over a decade ago, five researchers published a paper proposing the Hallmarks of Aging paradigm: a set of cellular and molecular processes that underlie the aging process in different organisms. These hallmarks encompass a range of interconnected pathways, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient signaling, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Together, the hallmarks contribute to the gradual decline in physiological function and increased susceptibility to age-related diseases that occurs with age, and provide a framework for understanding how we age.

In this episode, Matt takes us through a quick download of each hallmark of aging, talks about some of the paradigm's shortcomings and limitations, and discusses the implications of the Hallmarks of Aging paradigm for the geroscience field.

0:00 Trailer
0:44 Introduction
2:30 Definition of the hallmarks of aging
4:40 Criteria 1: Age-associated manifestation
6:43 Criticisms of the hallmarks of aging
8:36 The current version of the hallmarks of aging
9:00 Genomic instability
10:27 Telomere attrition
12:40 Epigenetic alterations
15:32 Loss of proteostasis
17:40 Disabled macroautophagy
20:17 Deregulated nutrient signaling
21:57 Mitochondrial dysfunction
23:13 Cellular senescence
27:13 Stem cell exhaustion
29:50 Altered intercellular communication
30:47 Chronic inflammation + "inflammaging"
32:09 Dysbiosis
33:43 The interconnectedness of hallmarks
35:48 Our rudimentary understanding of biological aging
40:37 Advice for the field
40:48 Pillars of aging and their impact on the aging process

Producers: Tara Mei, Nicholas Arapis
Video Editor: Jacob Keliikoa

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https://www.optispan.life/

Hi, I'm Matt Kaeberlein. I spent the first few decades of my career doing scientific research into the biology of aging, trying to understand the finer details of how humans age in order to facilitate translational interventions that promote healthspan and improve quality of life. Now I want to take some of that knowledge out of the lab and into the hands of people who can really use it.

On this channel I talk about all things aging and healthspan, from supplements and nutrition to the latest discoveries in longevity research. My goal is to lift the veil on the geroscience and longevity world and help you apply what we know to your own personal health trajectory. I care about quality science and will always be honest about what I don't know. I hope you'll find these videos helpful!