![]() In this paper, we discuss the scientific challenges that the fascinating discovery of “DNA methylation clocks” has brought into focus. The stability of 5mC in biological samples, even from long-term stored DNA, brings large-scale data availability, for use in subsequent high-throughput analysis. DNA methylation (5′methylcytosine, 5mC) is the most common DNA modification and predominantly occurs at cytosines in a CpG dinucleotide context in differentiated mammalian cells. Subsequently, these clocks were reported to capture aspects of biological aging and its associated morbidity and mortality. These high-resolution data enabled the construction of extremely accurate age estimators, termed “Epigenetic” or “DNA methylation clocks”. However, the association between epigenetic modifications and age became most starkly apparent with the arrival of the first high-throughput arrays measuring DNA methylation. Observations of age impacting on this mechanism have been reported for more than 50 years and suggested a role in age-related disease. Epigenetics encapsulates the chemical modifications and packaging of the genome that influence or indicate its activity, with strict definitions requiring inheritance through mitotic cell division. In this decade, we have discovered the remarkable power of epigenetic changes to estimate an individual’s age. Therefore, many biological measures, such as p16 ink4a tissue levels, circulating CRP, creatinine, and fasting glucose, as well as telomere length all correlate with aging. The cellular and molecular hallmarks of aging include changes associated with cell senescence, dysregulated nutrient sensing, and stem cell exhaustion, among others. It would also aid in testing interventions that attempt to modulate the aging process. Measurement of this relative “biological” aging may allow pre-emptive targeted health-promoting interventions, perhaps in a personalized and disease-specific fashion. There is considerable population variation in the rate at which people visibly age as well as become impaired by age-related frailty and disease. This aim of maximizing the “healthspan” makes obtaining accurate measures of aging-related pathology essential, to gauge its speed, decipher the changes that occur, and potentially unlock how aging acts as a disease risk factor. ![]() Increasing the productivity and reducing the disease affliction in these extended years7 would be clearly beneficial for both the individual and society. This leads to the undesirable outcome of many years of this prolonged lifespan being spent in ill health, with an associated massive health care burden. However, the success in reducing mortality has not been matched with a reduction in chronic disease. This demographic phenomenon is changing our societal make-up, from only ~130 million being 65 years or older (~5% of the world population) in 1950, to a predicted ~1.6 billion people (~17%) by 2050. Alongside this, the unprecedented gain in the average lifespan in humans, since the mid-twentieth century, has dramatically increased both the number of older people and their proportion in the population. This review summarizes the current knowledge on biological age biomarkers, factors influencing biological aging, and antiaging interventions, with a focus on vascular aspects of the aging process and its cardiovascular disease related manifestations.A key question in biology is to understand why and how we age. However, strategies to extend health span and life span require understanding of interindividual differences in age-dependent functional decline, known as biological aging. Studies in experimental models and humans have identified 9 highly interconnected hallmark processes driving mammalian aging. In a progressively aging population, it is essential to develop early-life biomarkers that efficiently identify individuals who are at high risk of developing accelerated vascular damage, with the ultimate goal of improving primary prevention and reducing the health care and socioeconomic impact of age-related cardiovascular disease. Aging is the main risk factor for vascular disease and ensuing cardiovascular and cerebrovascular events, the leading causes of death worldwide.
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