**1. Introduction**

Dietary fats occur naturally in various foods and their excessive consumption negatively impacts human health; dietary fat consumption can confer benefits, albeit also adverse effects concerning the onset and progression of several nutrition-related chronic diseases [1]. The use of fats of either plant or animal origin is embedded in practically every food culture as fats provide energy and lipid soluble vitamins, facilitate food preservation, and greatly contribute to food's sensorial characteristics. Amongst dietary fats, the consumption of plant oils is considered to render the greatest health benefits as they contain a higher proportion of unsaturated fatty acids compared to animal fats [2]. Thus, plant oils are a vital and beneficial source of energy. The most commonly consumed types of plant oils include palm, soybean, canola, sunflower-seed, and, most prominently, olive oil [3].

Olive oil in particular is an essential component of the Mediterranean diet and its frequent consumption is associated with a multitude of health benefits [4], including the deterrence of cardiovascular diseases [5], diabetes mellitus [6], metabolic syndrome [7], and several types of cancers [8]. Therefore, the differential impact of olive oil consumption, as compared to the ingestion of other plant oils, has been gaining increasing interest. A relatively recent meta-analysis of 32 cohorts (*n* = 841,211) demonstrated that the higher consumption of monounsaturated fatty acids (highest vs. lowest third) is associated with lower cardiovascular mortality (relative risk (R.R.): 0.88, 95% CI: 0.80–0.96), stroke (R.R.: 0.83, 95% CI: 0.71–0.97), and all-cause mortality (R.R.: 0.89, 95% CI: 0.83–0.96). It is noteworthy, though, that subgroup analyses revealed that these effects were attributed primarily to olive oil consumption, and not to the combined consumption of monounsaturated fatty acids arising from both plant and animal origins [9]. In addition, preliminary findings reveal that the frequent consumption of olive oil may also beneficially impact the aging process [10,11].

Aging is a multifactorial process involving different alterations regarded as the "hallmarks of aging". These hallmarks include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intracellular communication [12]. These hallmarks are influenced by olive oil intake, among other factors. Specifically, several of such effects may be accounted for by oleic acid (a main constituent of olive oil) and the bioactivity of its minor compounds (such as polyphenols), which as a result of their ability to modulate gene expression, may affect cellular aging through both direct and indirect mechanisms. In fact, one of the major phenol classes present in olive oil, secoiridoids, exhibits the capacity to modulate several pathways entailed in aging. These beneficial effects have been observed in both in vitro and in vivo animal models [13] as well as in human studies, revealing the potential beneficial effects of olive oil intake on the aging process [12].

Although olive oil and its compounds have beneficial effects on aging at the cellular level, there is still a lack of evidence regarding the role of olive oil in the concept of successful aging at a human level. Thus, the aim of this study was to elucidate the association of exclusive consumption of olive oil with successful aging, in people over the age of 50—a period of subtle changes in the human body—living in Greece.

#### **2. Materials and Methods**

The data from two cross-sectional, population-based, large-scale epidemiologic studies (namely the ATTICA [14] and the MEDIS (MEDiterranean Islands Study) [15] studies), conducted in Greece, were combined for the purposes of the present investigation.

## *2.1. Study Sample*

Data from both the ATTICA and the MEDIS studies included the information collected from adults aged over 50 years living in urban and insular Greek areas. The ATTICA study was a population-based observational study implemented in the greater metropolitan Athens area in Greece during 2001–2002. The main aims of this study were to investigate the prevalence of cardiovascular disease risk factors, potential predictor factors of cardiovascular disease (CVD), and the 10-year (2002–2012) incidence of the disease [14]. At baseline, all participants were free of CVD and cancer, as assessed through a detailed clinical evaluation by the study's physicians. From the original sample aged >18 years (*n =* 2583), a sub-group of *n* = 1128 individuals aged >50 years old were analyzed for the purposes of the present work. Additionally, approximately 3000 older people from Mani (Greek peninsula region) and 26 Mediterranean islands of 5 countries were enrolled during 2005–2017 (MEDIS study). Individuals who resided in assisted-living centers, had a clinical history of CVD or cancer, or had left the island for a considerable period of time during their life (i.e., >5 years) were excluded. From the *n* = 3138 participants over 50 years old living in the insular Mediterranean region, of the MEDIS study, a sub-group of *n* = 2221 individuals from 20 Greek islands only were analyzed in this work. More information about the MEDIS study may be found elsewhere [15]. In both studies, a group of health scientists (cardiologists, general practitioners, physicians, dietitians, public health nutritionists, and nurses) with field experience collected all required information using standard, validated questionnaires and clinical procedures.
