What if there was a way to measure our biological age? And what if there were strategies to slow down—or even reverse—the aging process? The answers to these questions lie at the heart of the groundbreaking work Dr. Morgan Levine is doing in her lab at Yale.

True Age introduces readers to the latest developments in the science of aging and longevity. It provides an in-depth understanding of biological age and the methods now available to estimate our own. It helps us target an individualized plan to eat, exercise, and sleep, as well as pointing to other lifestyle practices like intermittent fasting and caloric restriction that have been shown to slow or reverse the aging process.

Book Review

This brief review of True Age by Morgan Levine is probably slightly jaundiced by not having read the blurb in advance. I was really excited to hear what one of the leading experts on epigenetic clocks had to say and to discover more about the science - but that's not what this book is about.

True Age provides a good introduction to the concept of biological age, that we're not all ageing at the same rate, and uses some interesting analogies to do so. Sometimes the detours, for me, went a bit too far away from the main subject (for example there was discussion of women in the workplace and Aesop's boy who called wolf fable) but perhaps those make it more enjoyable reading for those new to the subject and want to be guided into the science.

Key Points of True Age

Here are the notes I highlighted when reading Morgan Levine's book:

• epigenetics is the “operating system of the cell”
• epigenetic code changes as we age
• biological changes taking place among the molecules and cells in our body renders each of us more susceptible to disease
• biological aging is the single greatest risk factor for disease and death
• breast tissue from women with cancer appeared biologically older than the tissue from women without cancer
• fatty liver disease was associated with older biological age
• biological aging in different organs appears to drive the development of disease
• biological aging is malleable
• acute mild stressors actually boost resilience, e.g. exercise and caloric restriction (CR)
• mild stress sends a signal to your body that it needs to toughen up
• extreme stress can actually have the opposite effect
• possible to exercise too much or eat too little
• there isn’t an overall consensus on how to estimate biological age
• scientists are arguing whether aging is a pre-specified program or an unfortunate cost
• I define aging as a “loss of specificity”
• female honeybees' diet has the potential to increase longevity four- to tenfold
• most people develop disease in their sixties and may survive another twenty years
• I consider the significance of healthspan extension to be so great that I have devoted my entire career to the cause
• direct cause of epigenetic changes is not known
• one hypothesis is that they reflect random errors, e.g. epigenetic marks are copied over correctly
• another possibility is it's the cell’s response to a failing system, i.e. cells change their behavior as part of a programmed stress response
• senescent cells chronically activate pro-inflammatory genes
• in the aging process, we observe a decline in the number of available stem cells
• age-related mutations of epigenetic changes can increase a stem cell’s self-renewal
• our cells compete, just as different individuals within a species do
• the etiologies of all chronic diseases actually lie on a continuum.
• with every condition you develop, it takes less time for you to develop another
• Frailty Index can really only be used to track aging once diseases and conditions have started to manifest
• leukocyte telomere length (LTL) appeared to exhibit fairly weak associations with age
• telomere length is more likely to be shorter in cells that rapidly divide and replace themselves
• “phenotypic age” refers to a characteristic aging profile of an individual that is influenced by both genetic and nongenetic factors
• able to predict who would survive the next ten years and who wouldn’t, with approximately 90 percent accuracy,
• biggest determinants of a person’s biological aging (in order of impact) = health behaviors, recent stressors and adversities, genetics
• the signs of aging are best fought from the inside out
• DNA methylation refers to a chemical tag (methyl group) that is added to one of the nucleotides
• these chemical tags throughout your genome become substantially altered as we age
• Dr. Horvath developed a DNA methylation age predictor that could estimate age with extremely high accuracy
• I moved across town from USC to UCLA to start a postdoc position in his lab
• people who ate more leafy greens, exercised, and had higher education tended to be epigenetically younger
• insomnia was linked to faster epigenetic aging
• out of 181 countries for which sex-specific data is available, there is not a single one in which men outlive women
• in centenarians women still experience much more disease prevalence
• individual yeast tend to take one of two aging paths (nucleoli or mitochondrial degradation)
• individual organisms determine which systems to maintain at the expense of others
• APOE is a protein that helps to transport cholesterol around the body,
• APOE genotype relates to a person’s risk of developing Alzheimer’s disease (up to elevenfold), cardiovascular disease, and even a shorter life expectancy
• your genes influence on the probability you will develop the a disease pales in comparison to the effect aging has on that probability
• thousands of genes likely combine to influence your susceptibility to different aspects of aging
• best reference point for determining how you are aging is your younger self
• scientists, including myself, are working diligently to develop ways to predict how best to slow biological aging for a given person
• reducing calories below standard levels actually extended both the median and maximal life span of rats
• CRON-diet (Calorie Restriction with Optimal Nutrition) - men consume approx. 1,200 to 2,400 calories a day and women 1,000 and 1,800
• one problem with attributing health success to CR alone is that people who engage in the practice are driven to be as healthy as possible
• in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) study, those assigned to a CR diet only gained about three months of biological age over the entire two-year period
• recent research is finding that slashing carbohydrate intake may actually shorten your life span
• New data have linked the consumption of high amounts of animal protein to aging and disease
• the number of fat cells in our bodies (called “adipocytes”) may not fluctuate as much as was once believed - instead, weight changes are due more to alterations in the size of those cells
• majority of adverse outcomes associated with obesity seem to be caused by increases in adipocyte volume and dysfunction
• healthy weight should be personalized to our unique characteristics
• human growth hormone and IGF-1 have been shown to promote aging and cancer
• high plant-based protein did not seem to be a problem
• methionine and tryptophan (two essential amino acids) have been identified as potentially pro-aging when eaten in high amounts
• when people move away from "Blue Zones" they tend to lose their longevity advantage
• good evidence that fasting is in many ways just "CR lite"
• for many animal studies calories were restricted by feeding animals only once a day
• fasting-mimicking diet (FMD) showed significant reduction in BMI, total fat, subcutaneous fat, and visceral fat
• fasting was also associated with improvements in insulin sensitivity and reductions in blood sugar
• after three cycles of FMD, subjects appeared approximately 2.5 years younger
• Versions of FMD include Alternate-Day Fasting (ADF) and Time-Restricted Eating (TRE)
• keto seems to be best in moderation
• not everyone will respond in the same way to any given diet
• skeletal and muscular systems of humans evolved in a manner that appears specifically designed for running very long distances
• everything we see in aging is only accelerated by lack of exercise
• our built environments promote sedentism
• in response to regular physical activity
•  - number and size of mitochondria in our cells increase 
•  - leads to downregulation of inflammatory pathways
•  - Gpld1 is expressed by the liver
• there doesn’t seem to be an age in which the risks of being active outweigh the benefits
• HIIT helps develop an adaptive stress response
• ultramarathoners have decreased healthspan and life span compared to regular runners
• deep sleep seems to be the major player when it comes to physical revitalization
• clearing waste from our brains is driven in part by the shortwave oscillations, called “delta waves,” that manifest during deep sleep
• CSF that flows through our spinal cord and brain cavity is continuously replaced every eight hours
• link between sleep duration and outcomes of health is U-shaped
• optimal level centers somewhere around seven hours a night
• in mice, slight overexpression of SIRT1 has been shown to protect against cancer, senescence, oxidative stress, and DNA damage
• our bodies can quickly adjust to melatonin supplementation
• “cognitive behavioral therapy for insomnia” (CBT-I)is one of the best treatments for insomnia
• VA's Insomnia Coach is rreely available to all
• more than a third of us experience continuous anxiety
• what happens in our brain directly connects to physiology in the rest of our body
• in the face of psychosocial stressors, your brain will activate the HPA axis
• sustained levels of elevated cortisol can wear down our system
• SNS activity can impact the expansion of white blood cell populations
• the constant activation of CTRA may promote inflammation
• how we perceive the stress in our lives may be more important to our health and aging than the events themselves
• evidence highlights various links between poor health and living within a disadvantaged community
• socioeconomic status also has a profound impact on stress
• adversity and low socioeconomic status in adulthood accounted for nearly 12% of the differences in biological aging rates between individuals
• early life experiences have lasting effects on stress signaling and health outcomes
• African Americans were on average three years older biologically than whites of the same chronological age
• epigenetic signatures may uncover things like optimal diet or exercise for an individual
• 23,000 emergency department visits in the United States each year were due to adverse reactions to dietary supplements
• rapamycin increases survival in male and female mice by 9 and 14 percent, respectively
• Novartis has its eye on rapalogs as a potential aging therapeutic
• injecting senescent cells into mice produces an acceleration of aging phenotypes
• exposure to young blood can rejuvenate many aging-related changes
• simply diluting old blood with a mixture of saline and albumin can achieve similar results
• reprogramming with Yamanaka factors appears to reset our cells’ aging clock
• the aging signature is the first thing to be reversed, before the cells convert back to stemlike states