**1. Introduction**

Globally, life expectancy has increased by nearly 20 years in both sexes since the 1950s [1]. In the United States (US) in 2015, life expectancy at birth was calculated to be almost 79 years old for both males and females [2]. While these numbers are encouraging, the quality of life of these individuals has not increased along with this increased life expectancy [3]. There are many factors that can influence quality of life but chronic diseases such as osteoporosis, osteoarthritis, heart disease, sarcopenia, type 2 diabetes (T2D), and dementia all play a role in the quality of life (QOL) of aging individuals.

Many chronic diseases are highly preventable and are generally treatable through diet and exercise. Indeed, poor diet and inadequate physical activity are two of the three most common risk factors for several chronic diseases, and addressing these factors in addition to the third risk factor, smoking, reduces the risk of cardiovascular disease (CVD), stroke, and T2D by 80% [4]. A 2013 study which analyzed the effect of physical inactivity on chronic disease estimated that, worldwide, physical inactivity is linked to 6–10% of chronic diseases that included CVD, T2D, breast cancer, and colon cancer, and that inactivity is associated 9% of premature deaths [5].

Knee osteoarthritis (OA) has been ranked as one of the top contributors to global disabilities in the world [6]. Osteoarthritis is a degenerative disorder of synovial joints characterized by focal loss of articular cartilage with reactive changes in subchondral and marginal bone, synovium and para-articular structures [7]. These degenerative changes lead to the primary complaints of pain with movement, stiffness, instability, and loss of function, particularly in those with knee OA [8].

The World Health Organization (WHO) estimates that about 10% of individuals 60 years or older have OA, an estimate that will only increase as the world's population continues to age due to longer life expectancies [9]. The conclusive etiology of this disease is unknown, but injury to the joint, age, gender, and obesity are all known factors to contribute to the development of OA [10]. There is also mounting evidence that leptin may play a key role in the pathophysiology of OA. Leptin concentration in the serum is positively correlated with Body Mass Index (BMI) [11, 12]. This finding is significant as it helps to explain why obesity is a risk factor for OA, even in non-weight bearing joints such as hands.

Because individuals with OA are in constant pain, they are likely to stop exercising or to engage in any physical activity, thus increasing their risk of morbidity. It may also lead to other chronic diseases, both as a result of the lack of exercise, and the possibility of weight gain and the risks associated with excess weight. In fact, T2D has been shown to be a risk factor for knee OA progression [13], indicating that these disease states feed off of each other. While exercise is incredibly important for health, nutrition may be a much more helpful and significant treatment for individuals with chronic diseases, specifically OA, because the source of many of these diseases is underlying inflammation [14] and treating the inflammation through dietary change may result in the treatment of multiple disease states.

Although OA affects a large number of Americans, there are no proven therapies for preventing or halting its progression. In the normal joint, there is a balance between synthesis and degradation of cartilage. In inflammatory conditions such as OA, and other chronic diseases, catabolic molecules are upregulated, thereby interrupting the function of anabolic molecules [15]. Catabolic cytokines also induce the production of specific matrix degrading metalloproteases, causing cartilage degradation [16]. This finding has been confirmed by the increased level of these cytokines in people with OA [17]. Unregulated or excess production of these molecules may play a detrimental role in the pathophysiology of OA [16, 18].

The development of OA is also accompanied by increased production of prostaglandins (PGs), molecules that may contribute to joint damage, pain, and inflammation [19]. Cyclooxygenase (COX) is responsible for the production of PGs and exists as two distinct isoforms, COX-1, and COX-2. Increased expression of COX-2 has been demonstrated in synovial tissues suggesting that COX-2 expression mediates the inflammatory response in OA [20]. COX-2 is undetectable in most tissues, but is increased in inflammation leading to overproduction of PGE2 [21, 22]. Inhibition of these enzymes by nonsteroidal anti-inflammatory drugs (NSAID) and selective COX-2 inhibitors reduces the levels of PGs, resulting in a reduction in pain and inflammation.

Finding nutritional interventions to target the COX-2 pathway while allowing other necessary inflammatory pathways to function would significantly increase quality of life as well as functionality of individuals with OA. It may also inadvertently target unregulated inflammation that has been associated with other chronic disease states, and allow for affected individuals to exercise thus further decreasing their risk for the aforementioned chronic diseases.

Soy appears to be a promising treatment for those with OA, and has many other health benefits. Soy protein is low in saturated fat, contains all of the essential amino acids, and is also a good source of fiber, iron, calcium, zinc, and B vitamins [23]. This book chapter will focus on soy and its relationship to OA and other chronic diseases.
