Aging clock
Theory of Aging
Programmed theory (Costa et al. 2016)
- Our DNA has a “self-destruct” instruction
- Aging is controlled by our DNA
Damage/Error theory (Halliwell and Gutteridge 2015)
- Aging is an accumulation of our body damages
- Aging is controlled by our exposure to aging factors
Hallmarks of aging
- Primary (damage initiators)
- Genomic instability
- Telomere attrition
- Epigenetic alterations
- Loss of proteostasis
- Disabled macroautophagy
- Antagonistic (responses that become harmful when overactive)
- Integrative (downstream, system-level failures)
Overview of DNA
- DNA is a recipe for our body to create different proteins to sustain our body functions
- Mutation of DNA (genomic instability) could consequently result in cancer or aging
Turning off gene - epigenetics
- Expression of gene could be turned on and off
- Your eyes and heart consist of different cells
- Unintentionally turn on and off could cause illness
- The study of the mechanism of turning on/off genes without modifying DNA is called Epigenetics
Epigenetic clocks
- From the damage theory perspective, researchers guess
- Turning off (methylation) some genes should be highly associated with age
AI in searching the switch
- There are approximately 20,000 genes in humans
- Identifying which switch is associated with aging is challenging
- AI and big data to search those switches
AI in searching the switch
- Hypermethylation: Over methylation, fewer switches being turned on
- Hypomethylation: Under methylation, more switches being turned on
Increasing clincal relevance
- Estimating age could bring little knowledge to the clinical setting
- Researchers start to explore different outcomes
- First generation (Chronological)
- Horvath Clock
- Hannum Clock
- Second generation (Clinical outcome: mortality, cancer, and etc.)
- GrimAge
- Levine/Phenoage
- Third generation (Pace of aging)
- DunedinPACE
- Levine/Phenoage
Insight to keep young
- Outliers from the epigenetic clock could bring some insights
- AI predicts older than actual age
- Potentially aging faster than people of the same age
- AI predicts younger than actual age
- Potentially aging slower than people of the same age
AI in searching key to young
- The effect of DNA methylation is reversible
- There is a chance for scientist to identify what kind of factors could benefit reversing methylation
- AI is used to identify common characteristics for people with accelerated and decelerated aging, including:
Factors affecting aging clock - Overview
- Factors are in a few categories
- Hereditary factors
- Disorder/disease
- Balanced body microsystems
- Lifestyles
Environmental factors
- Pollutants: Metals, pesticides, and air pollutants (Sharavanan et al. 2020)
- UV: UV exposure affects age-dependent methylation patterns (Grönniger et al. 2010)
- Social determinant of health (Krieger et al. 2024)
- Economic injustice
- Low parental educational level
- Adult impoverishment
- Microbiome: Diversity and composition of the gut microbiota (Begum et al. 2022)
Lifestyle factors
- Smoking/vaping: hypomethylation of AHHR (Philibert, Beach, and Brody 2012)
- Diet and Nutrients: Vitamins E, B12, affect epigenetic features (Bishop and Ferguson 2015)
- Exercise: Regular exercise is associated with a younger biological age Światowy et al. (2021)
- Maternal diet: Nutrient deficiency during maternal diet affects offspring’s DNA methylation patterns (Chmurzynska 2010)
- Stress: Stress-induced epigenetic changes can accumulate throughout life span (Zannas and Chrousos 2017)
- Sleep: Insufficient sleep duration at 6 months postpartum(Carroll et al. 2021)
Appearance and gene
- Phenotype: Observable characteristics or traits of an organism
- Phenotype is the interaction of genes plus environment (nature and nurture)
- Example: Twins with similar but not exactly identical appearance
Implication
Your appearance is modifiable
Guessing age from your photo
Mechanism
- AI will extract relevant features from the image
- Making predictions based on the features
Play around !
Instruction
Please record:
- Which website you use
- AI underestimate/overestimate/ perfectly predict your age
- Try repeating a few times using different models/pictures
Guess who is younger?
Guess who is younger?
DNA methylation - chemical switch
- Definition: methyl group (\(\text{-CH}_3\)) attached to the DNA
- Primarily refers to \(\text{-CH}_3\) on the 5th carbon of cytosine (C), creating 5-methylcytosine (5mC)
- Other forms include 6mA and 4mC
DNA methylation - mechanism
- Before the gene, there will be a lot of cytosine(C) before a gene, which control the gene is expressed or not
- Methylation will force the switch to turn off.
