Ayurveda and The Science of Aging

1. Introduction

Aging has been defined as the total sum of physiological changes that progressively leads to the death of the individual. It is also defined as the intrinsic, inevitable, and irreversible age-associated loss of viability that render us more susceptible to a number of diseases and death or a progressive functional decline of physiological function and a decrease in fecundity with age [1], [2], [3], [4]. Undoubtedly, human aging is associated with a wide range of physiological and cellular changes that limit our normal functions and make us more susceptible to death. Aging has two main components, Chronological Aging which refers to the actual age of the person in terms of years, months, and days. This component of aging is unstoppable, unchangeable and irreversible. Physiological/Biological aging is the second component and refers to an individual's development and changes based on certain cellular or molecular parameters. This involves looking at the individuals as they are and as they function, and not when they are born [5], [6]. Thus, biological aging is a set of processes that triggers deterioration of health and ultimately to death as a function of chronological age. Unlike chronological aging, biological aging can be reversed or delayed [5], [6]. Other terms that constitute aging include:

Lifespan: It is the period of time during which we are alive. Lifespan also includes the years spent in poor health as there are several age-associated health conditions that lack proper treatment or cure [7], [8].

Morbidity: The period of ill health during an individual's lifespan is referred to as morbidity. Although our lifespans have increased significantly due to better nutrition and modern medicine, middle-aged and elderly people suffer many years of ill health before they die. Age-associated diseases include heart disease, stroke, diabetes, osteoporosis, and other chronic problems resulting in the individual being in a state of morbid condition [7], [8].

Healthspan: Health span is equal to the lifespan devoid of the amount of time an individual spends in ill health (Lifespan–morbidity). This is the period in an individual's life during which the person is generally healthy and free from serious or chronic illness. Thus, healthspan refers to how long an individual lives a disease-free healthy life [4], [9], [10].

Therefore, biological aging in terms of healthspan is a result of complex structural and functional changes across molecules, cells, tissues and whole body systems. Its manifestation is influenced by several factors including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intra-and intercellular communication. Since aging is accompanied by impairment of normal physiological functioning of cells, tissue, organs and bodily systems that increases the risk of death, some in the aging field consider aging itself to be a deadly disease [11], [12].

There is no one single cause or trigger of the aging phenomenon as there are many different and often conflicting theories of aging. At the cellular level, changes that contribute to aging include reduction in stem cell proliferation in a number of tissues, accumulation of toxic protein aggregates and free radicals, accumulation of senescent cells that trigger inflammation and impairment in mitochondrial function. At the genomic level, accumulation of mutations in DNA together with faulty DNA repair processes and telomere shortening are all associated with early signs of aging. Several researchers believe that a combination of several of these factors may contribute to overall aging [13], [14], [15], [16]. Theories of aging include but are not limited to a) Genetic theory of aging, b) Damage or Error theory, c) Dilman's Neuroendocrine theory, d) DNA damage theory, e) Free radical damage theory, f) Gene mutations, g) Cell divisions/telomere shortening, h) Cellular senescence and i) Antagonistic Pleiotropy [12], [13], [14], [15], [16]. Some of these causes may appear non-specific with regard to suitable interventions, because it is unclear which among them is more amenable to pharmacological intervention in order to reverse the aging process.

2. Factors that promote biological aging

While aging in itself is inevitable, there are ways to reduce or delay the pathological effects of aging. This involves looking at strategies to combat aging both at the cellular and/or genomic level and to see if any of the above mentioned triggers of aging are amenable to suitable drug interventions. Researchers propose at least seven highly intertwined processes that promote aging, thus providing a format for the identification of program mediators and therapeutic candidates. Deciphering these factors that are also responsible for age-associated diseases will be helpful in drug discovery efforts to decelerate aging [4], [9]. Among these factors, one that has inspired a lot of excitement is metabolism, and researchers have been trying to understand why caloric restriction extends the life span in mice and other animals [17], [18], [19], [20], [21]. Metabolizing fewer calories could result in reduced oxidative damage or alternatively, absence of nutrients may trigger certain defense mechanisms that protect the body from decaying. Researchers have managed to identify several molecular pathways that govern metabolism. Modification of these pathways or their specific products through proper drug-based interventions, could one day mimic the life expanding effects of caloric restriction in humans without compromising on the food intake [16], [19], [20], [21], [22], [23].

Another factor that is being thoroughly explored is the fallout from long term chronic inflammation. While several age-associated diseases involve the inflammatory process, long lived healthy individuals including centenarians are generally free from age-associated inflammatory diseases [24], [25], [26]. Interventions targeted to reduce chronic inflammation are being examined closely for their life enhancing effects [27], [28], [29]. Inflammation cannot be completely shut down as our bodies need the short term adaptive inflammatory process to fight infections and ward off short term stress [30], [31], [32]. Thus, we need to better understand the inflammatory process at a molecular level to see if drugs can be developed that specifically target the aberrant pathways.

In addition, extension of lifespan in humans could also be achieved by lowering the rate of free radical induced-oxidative damage to tissues, replacement and/or rejuvenation of damaged tissues and cells, reversal of harmful epigenetic changes, or enhancing the telomerase activity [33], [34], [35]. Several experts are also developing strategies to combat multiple age-associated diseases at the same time [23], [36].

Aging is a major risk factor for most chronic diseases and researchers agree that if we can address the issue of aging itself, we could potentially delay and diminish age-associated diseases all at once [11], [12]. Researchers are looking at slowing down aging with the premise that a drug targeting the aging process will not only slow down aging but will also delay age-associated pathologies and diseases [37], [38]. This approach is very attractive as researchers do not need to discover drugs to combat specific age-associated conditions like cancer, diabetes or dementia, but instead treat the aging process itself [4], [9], [37], [38].

1) The free-radical theory of aging suggests that antioxidant supplements, such as vitamin C, vitamin E, Q10, lipoic acid, carnosine, and N-acetylcysteine, might extend human life. However, despite several studies, it is not clear if β-carotene supplements and high doses of vitamin E extend life span or increase mortality rates [28], [39], [40].

2) Resveratrol is a sirtuin stimulant that has been shown to extend life in animal models, but the effect of resveratrol on lifespan in humans is unclear [41], [42], [43], [44].

3) The anti-diabetes drug metformin has shown to extend the life of animals and the US-FDA has permitted a clinical trial to see if the life-extending benefits replicate in humans. If metformin turns out to be successful in delaying the aging process, a person taking metformin would be young at 90 [44], [45], [46].

4) Drugs like acarbose (a common drug prescribed for Type 2 diabetes), and anti-inflammatory drugs such as masoprocol and basic aspirin extend lifespan in mice, but these drugs can have multiple effects, and their mechanism of action is not clear. The fact that they tackle chronic inflammation could just be one piece of the puzzle, not the whole solution [47], [48], [49].

5) The most promising drug to combat aging has been rapamycin, an immunosuppressant often used in organ transplants. In addition to life span extension, rapamycin has an unbelievably wide range of effects in mice ranging from preventing Alzheimer's and cardiovascular disease to reducing cancer [44], [50], [51].

6) Non-drug therapies that extend lifespan include calorie restriction (CR). CR also retards age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast. The mechanism through which this occurs is unclear [17], [18], [19], [20], [21].

7) Therapeutic cloning, body part replacement and stem cell research could one day provide a way to generate cells, body parts, or even entire bodies that do not decay [52], [53], [54]. Researchers have succeeded in growing artificial body parts in the lab, including nose, ears, tear ducts, bladders and blood vessels from human stem cells. The use of human stem cells for the purpose of cultivating organs, that can be transplanted into people, is another attractive approach to combat age-associated organ decay [55], [56], [57], [58].

4. Ayurveda and science of aging

Jara also called as Vardhakya (aging) is defined as that which has become old by the act of wearing out. According to Ayurveda, Jara/aging is not a disease but a natural phenomenon like hunger, thirst or sleep. In the theory of natural destructions (Swabhavoparamavada), Charaka describes that there is a causative factor for the manifestation of a being but there is no cause for the cessation of this manifestation, since death following birth is a state of natural flow [59], [60]. The term Jara denotes four entities: Nityaga which signifies continuation of consciousness, Dhari which denotes the factor(s) that prevent the body from Jara/aging, Jeevitam which represents the act of keeping alive and Anubandha that denotes transmigration of the body [59], [60]. Accordingly, Jara/aging is influenced by factors affecting Shareera (physical), Indriya (emotional), Satwa (psychic level), Agni (metabolism) and Bala/Ojas (immunity). In addition, Parinama (cellular transformation), Sharira vriddhikara bhavas (genotypic and phenotypic characteristics) and Garbhahinivrittikara bhava (pregnancy-induced fetal development and changes) also affect an individual's aging process [61], [62], [63].

Jara is accompanied by the process of decay and manifests in the form of various degenerative changes. Although these changes are natural (Kalaja Vriddhavastha-natural aging), they are not pleasant [62], [64]. Everyone is aware that a person who has taken birth must grow and finally die, but nobody wants to grow old and certainly no one wishes to die. Humans in general consider aging and age-associated diseases as unnatural even though our choices and actions are responsible for the rapid biological aging. Misusing the five senses (pancha tanmatras) and bringing in disharmonious impressions through the five sense organs (pancha jnanendriyas), making incorrect choices that promote unhealthy transformation of the body and mind (Parinama), all trigger the disease process resulting in mental and physical suffering [65]. Mental and physical ill-health weakens dhatusamya (homeostasis), resulting in Akalaja vriddhavastha (pathological aging) [61], [62], [66]. Ayurveda takes a holistic approach toward the maintenance of dhatusamya, a state of equilibrium of normal anatomical, biological, physiological, mental and spiritual well-being [66], [67]. Hence a balanced state (sama) of tissue (dhatu), energy systems (Dosha), heat of transformation (Agni) and metabolic wastes (mala) constitute homeostasis in Ayurveda that leads to healthy aging (Sukhayu/Kalaja Vriddhavastha) [66], [68]. Some of the most important factors that affect Jara/healthy aging include:

Kala Parinama (time and transformation) is one the most important and potent factors that influences Jara or aging as it includes all creation in itself [69], [70]. Kala Parinama refers to the physical and mental transformation that occurs as a function of time and as we age. Being out of harmony with the rhythms and cycles of nature can trigger unhealthy transformation and disharmonious changes, making the body vulnerable to disease and rapid aging [63], [65], [70]. Kala influences a human from conception till death and this time period is called Ayush (lifespan). Ayurveda divides Ayush into Vaya (various stages of life)—childhood (Bala-up to the age 16 years), adolescent/teenage (vivardhamana, 16–20 years of age), youth (youvana, 20–30 years), matured individual (sampoornata, 30–40 years), aged individual (parihani, 40–60 years) and older adults (last stage of life-Jirna or Vriddhavastha) [61]. Owing to the influence of Kala, various changes occur in the body during these stages of life and hence the lifestyle adopted during each stage of this growth has a profound influence on the aging process.

Prakruti refers to the biological constitution (anatomical, physiological and psychological) of an individual. The Prakruti which is unique to each individual reflects the baseline characteristics of the individual including metabolism, mental makeup, immunity, inherent strength and weakness and proclivities [67], [70], [71]. Thus, Prakruti determines an individual's capacity for transformation at the physical, mental and emotional levels owing to the interactions with internal and external stimuli all of which affect the aging process [63], [72].

Doshas or biological energy systems determine the longevity at the cellular level. Vata, which is closely related to pranic life energy, governs all life functions and biological activity and is the energy of movement. Pitta governs digestion and metabolism. Kapha controls anabolism and is the energy of building and lubrication that provides the body with physical form, structure, and the smooth functioning of all its parts. Health and disease is a direct reflection of the status and interaction of the Doshas in the body that in turn provokes or delays the aging process [71]. Proper diet, exercise and a harmonious lifestyle can create a balance among these Doshas ensuring a healthy healthspan [59], [61], [62].

Subtle Doshas are subtle counterparts of Doshas and an elaboration of the mental and emotional aspects of the physical Doshas that also influence the Jara/aging process. The subtle counterparts of the biological Vata, Pitta and Kapha Doshas are Prana (subtle life energy), Ojas (subtle immunity) and tejas (subtle vitality/subtle fire or energy) that are necessary for smooth longevity [59], [71], [73]. Prana controls breath, sensory perceptions and the thought process and thus is responsible for mind-body coordination. Tejas represents the digestion and transformation of sensory impressions, intelligence, thoughts, perception and awareness that results in a suitable action. Ojas represents robustness, strength and vitality and is responsible for the auto-immune system and mental resistance against stress. The lifespan and healthspan of an individual has a direct correlation with the person's status and integration of prana, tejas and Ojas [59], [71], [73].

Ahara (diet) is another important factor that influences aging/Jara. A poor or defective diet (GramyaAhara) together with disharmonious lifestyle triggers the vitiation of any or all three Doshas, leading to pathological changes and reduced lifespan [74], [75], [76]. Poor dietary practices include among others, improper timing of food intake, eating meals late at night, incorrect choices of food, consuming stale, processed or highly refined food, cold foods, eating in a noisy environment, and eating in a stressed mental state. An over-abundance of calories and the highly refined foods together with poor eating practices may lead to increased inflammation, reduced control of infection, increased rates of cancer, increased risk for allergic disease and reduced immunity (Ojas). These changes coupled with altered enthusiasm, insomnia, and lethargy can result in failure to live out the complete lifespan [74], [75], [77].

Achara (routines) refers to the physiological machinery that controls the circadian rhythm or the 24-h body clock and is another component that has an important role in the aging process. According to Ayurveda, the health of all living beings is governed by an internal clock that runs on a 24-h, light–dark cycle in conjunction with the sun and earth's movement. Ayurveda provides several guidelines about the operations of the body clock in terms of time and season-based routines called day routines (dinacharya), night routines (ratricharya) and seasonal routines (ritucharya) [63], [76]. These guidelines include optimal times to arise and sleep, breathing routines, elimination, bath, massage, exercise, diet, study, travel, and other pursuits. Ayurveda recommends healthy and harmonious lifestyle routines to sustain and maintain the synchronicity of the circadian rhythm that results in good health, vitality and immunity, all of which delay biological aging [63], [76]. Modern medicine recognizes these internal clocks as the circadian rhythms that are intimately tied to our health, well-being and the aging process. In humans, these biological clocks or circadian rhythms anticipate various activities throughout the day, from waking up to sleeping and eating. In addition, these clocks regulate hormone levels, body temperature, and metabolism.

Jatharagni (digestive fire) not only regulates the digestion, absorption and assimilation of food but also has a profound influence on the lifespan and healthspan of an individual. Jatharagni is the root of all the digestive fires in the body [78], [79]. Jatharagni serves as the central digestive fire and is the representation for all metabolic functions in the body. This includes the digestive function, cellular metabolism, sense perception, thought function and transformation of mental and emotional impressions [80], [81], [82]. If Jatharagni is too weak, the digestion of food is compromised resulting in malabsorption and accumulation of toxins (ama). If Jatharagni is too strong, it burns out the associated tissues resulting in tissue degeneration. Thus, the state of Jatharagni influences the aging process [80], [81], [82].

5. Ayurvedic recommendations for a successful healthspan

Unlike the modern medicine approach of seeking pills and supplements or replacing body parts to extend the healthspan of the individual, Ayurveda relies on a comprehensive program that includes dietary, lifestyle, behavioral and psychological intervention for extension of healthspan. The rationale for such a broad therapeutic intervention is to restore the normal balance and functioning of all the systems simultaneously at the level of the body, mind and emotions. The entire approach is a customized and individualized approach that covers the scope of all treatment procedures to enhance the healthspan of the individual and includes the following:

6. Conclusion

While there are various steps to manage the aging process, the modern medicine approach is different from the Ayurvedic approach. While neither approach is superior or inferior, the paramount difference lies in how both these sciences address the aging process. A subset of researchers consider aging itself to be a disease because, 1) aging is associated with an accumulation of cellular and molecular changes that impair normal physiology, 2) impairment of normal physiological functioning of cells, tissue, organs and bodily systems, in turn triggers age-associated diseases, and 3) aging itself is a risk factor for other diseases [11], [12]. Anti-aging approaches would therefore require an ideal disease-free physiological state at a certain age and a “to-do” list of drug interventions to keep the individual as close to that ideal state as possible. If aging is viewed as a disease as some researchers do, than the most logical approach would be to overcome the aging process with drugs like metformin, resveratrol, masoprocol, rapamycin and others. However, a drug approach de-emphasizes the enormous potential of disease prevention through lifestyle changes as the entire aging process is viewed in mechanistic and reductionistic terms that involve manipulating a specific pathway or molecules with powerful drugs [119], [120]. In contrast, a systems approach is designed to address multiple pathogenic mechanisms and optimizing the therapeutics for each of those targets [119], [120]. The past few decades of genetic and biochemical research have revealed an extensive network of molecular interactions involved in the aging process, suggesting that a systems approach or a network-based therapeutics approach, rather than a single target-based approach, may be feasible and potentially more effective for delaying or reversing the aging process.

Ayurveda considers aging as a natural and inevitable process and offers time-tested therapies for healthy aging. Ayurveda professes the principles of harmonious living and being in tune with nature, universal consciousness, environment, and individual constitution. Healthy aging would therefore require for the individual to bring in harmonious impressions, incorporate healthy lifestyle practices and routines that promote good health and well-being, and encourage healthy transformation of the body and mind through harmonious choices and actions. Unfortunately, lack of systematic safety and efficacy studies or proof-of-concept trials have relegated these Ayurvedic concepts of aging to a conceptual model. Thus, it is imperative that these concepts are revisited and re-examined to generate best research evidence that support these underlying principles, addresses causality, and minimizes bias and chance effects [121], [122], [123]. An important application of the Ayurvedic program described above is that a multi-component lifestyle system may serve as a platform on which these anti-aging drugs targeted to the patient's risk factors and that is likely to fail as a monotherapeutic, may succeed as key components of a “whole” therapeutic system. Thus, a combinatorial approach incorporating the best of modern medicine and Ayurvedic principles will ensure adding life to years and years to life.

Sources of funding

The Buck-Impact Circle Funds, The Lucas Brothers Foundation, The John and Bonnie Strauss Foundation and The Katherine Gehl Foundation.

Conflict of interest

None.