Congrats if you were one of us who saw that the French Paradox would eventually be more about anti-aging science than a narrow question of heart health and lifestyle, but few saw how far that journey would take us in a relatively few years. Seen through the lens of epigenetics – our genetic software, so to speak – anti-aging science is yielding fresh insights into the health effects of wine.
At first, the polyphenol antioxidant resveratrol looked like a unifying explanation for all that is healthy in wine. But it soon became apparent that there had to be more to it, and we now know that resveratrol produced only the first in a series of profound insights into the genetic underpinnings of aging, disease, health, and longevity. To a large extent, the genomic changes of aging are now seen as the same as those of age-related diseases (cardiovascular, neurologic, cancer). These changes can be measured independently from chronological age, and used to predict disease risk. This genie in the bottle is the revolutionary field of epigenetics, which many see as the basis for a sea change in health care and longevity. It’s looking like good news for wine lovers too.
Resveratrol, first identified in wine grape vines by French scientist Joseph Vercauteren, was considered by most to be just a novel antioxidant until a group at Harvard headed by geneticist David Sinclair, Ph.D. found a unique property. Resveratrol was identified as an activator of a class of gene regulators called sirtuins, which had earlier been shown to be responsible for the caloric restriction effect, known to extend lifespan under experimental conditions. Sirtuins promote or suppress genes involved in cellular repair and energy production in response to conditions such as reduced nutrient availability. Low nutrient conditions lead to a metabolic change that slows aging, mediated by sirtuins. Because resveratrol activates sirtuins it became the first known “caloric restriction mimetic.”
What sirtuins do is flip genetic switches on and off. Their role is essentially the same in wine grapes on the vine as in animals, including humans. These “switches” are found on proteins called histones, which organize and package DNA. Each time a gene switch is accessed, it is altered with a “tag” called methylation, leaving a record of gene expression and/or silencing. The lifetime log of methylations on genes associated with aging is the basis of determining biological age and rate of aging using AI-derived algorithms called methylation clocks. They are widely available now and increasingly reliable.
If genes are the pages in a reference manual, epigenetics is the dogeared corners and highlighter markups; or seen another way, if the genome is our biological hardware then the epigenome is software. Aging can thus be seen as a software problem that could be restored by rebooting! Sinclair tested this concept in an experiment that provoked accelerated aging in mice by causing DNA breaks (as happens in normal aging.) In results reported in February 2023, his group showed that the increased stress of DNA repair resulted in loss in epigenetic information, rather than changes in the DNA sequence itself, causing the mice to age faster. They then used a gene therapy technology that restored the epigenome and showed that it returned the organs and tissues to a youthful state, driving aging backwards. This “epigenetic reboot” led to improvement in numerous biomarkers of aging.
The epigenetic impact of alcohol and wine
A slightly less fantastical application of epigenetics is identification of the genomic signatures of various lifestyle factors and their impact on biological age. Several gene markers have been identified that reflect lifetime alcohol consumption, providing a unique way to measure the cumulative impact of alcohol. We shouldn’t be surprised that what emerges is the familiar U-shaped curve:
Deviation of biological age from chronological age using Hannum’s methylation age clock (modified from Beach et. al. 2015). For moderate drinking, aging is accelerated by either increasing or decreasing levels. Aging is expressed in years.
According to the authors of this multi-center study on 2 separate populations, “significant antiaging effects of alcohol were found in both data sets” and “consistent with prior epidemiological examinations, moderate alcohol consumption was associated with decelerated aging overall. The U-shaped curve found in the current study is similar to that found with respect to the effects of alcohol consumption on other health-related outcomes, including quality of life and bone density.”
Recent studies recapitulate a similar non-linear relationship between alcohol and epigenetic age. Encouragingly for us wine drinkers, there’s evidence that we may experience a greater degree of benefit. Data from a 20-year study called CARDIA [4] shows that while cumulative alcohol exposure and a pattern of binge drinking reveal accelerated aging on a methylation clock called GrimAge, this was not seen with wine consumption.
I believe we are indeed on the cusp of a revolutionary advance in health care and the science of aging. It’s good to know that we can still enjoy a glass of vino while we ponder the benefits of this amazing research, which owes its origins in no small measure to wine.
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References
- Beach SR, Dogan MV, Lei MK, Cutrona CE, Gerrard M, Gibbons FX, Simons RL, Brody GH, Philibert RA. Methylomic Aging as a Window onto the Influence of Lifestyle: Tobacco and Alcohol Use Alter the Rate of Biological Aging. J Am Geriatr Soc. 2015 Dec;63(12):2519-2525. doi: 10.1111/jgs.13830. Epub 2015 Nov 14. PMID: 26566992; PMCID: PMC4906951.
- Sinclair DA, LaPlante MD. Lifespan: Why we age – and why we don’t have to. Simon & Schuster 2019.
- Yang JH, Hayano M, Griffin PT, Amorim JA, Bonkowski MS, Apostolides JK, Salfati EL, Blanchette M, Munding EM, Bhakta M, Chew YC, Guo W, Yang X, Maybury-Lewis S, Tian X, Ross JM, Coppotelli G, Meer MV, Rogers-Hammond R, Vera DL, Lu YR, Pippin JW, Creswell ML, Dou Z, Xu C, Mitchell SJ, Das A, O’Connell BL, Thakur S, Kane AE, Su Q, Mohri Y, Nishimura EK, Schaevitz L, Garg N, Balta AM, Rego MA, Gregory-Ksander M, Jakobs TC, Zhong L, Wakimoto H, El Andari J, Grimm D, Mostoslavsky R, Wagers AJ, Tsubota K, Bonasera SJ, Palmeira CM, Seidman JG, Seidman CE, Wolf NS, Kreiling JA, Sedivy JM, Murphy GF, Green RE, Garcia BA, Berger SL, Oberdoerffer P, Shankland SJ, Gladyshev VN, Ksander BR, Pfenning AR, Rajman LA, Sinclair DA. Loss of epigenetic information as a cause of mammalian aging. Cell. 2023 Jan 19;186(2):305-326.e27. doi: 10.1016/j.cell.2022.12.027. Epub 2023 Jan 12. PMID: 36638792.
- Nannini DR, Joyce BT, Zheng Y, Gao T, Wang J, Liu L, Jacobs DR, Schreiner PJ, Liu C, Dai Q, Horvath S, Lu AT, Yaffe K, Greenland P, Lloyd-Jones DM, Hou L. Alcohol consumption and epigenetic age acceleration in young adults. Aging (Albany NY). 2023 Jan 5;15(2):371-395. doi: 10.18632/aging.204467. Epub 2023 Jan 5. PMID: 36622282; PMCID: PMC9925681.
Age Gets Better With Wine 