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Review

Life in the Years: Maximizing Physical and Cognitive Health in the Elderly

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07 November 2024

Posted:

08 November 2024

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Abstract

Biomarker-based tests are capable of predicting one’s biological age and mortality risk. To complement the suite of biomarker-based measurements, physical and cognitive performance tests can also improve the predictability of these measurement panels. Importantly, these measurements can be administered quite non-invasively and inexpensively, and training programs can be developed to improve parameters in aging. This will be a vital approach in improving the health of the aged and preventing massive healthcare expenditures at the end of life, which may become a serious fiscal issue if not addressed. This review touches on the ways people can measure function, the models that predict mortality based on this data, and the interventions that seek to improve these measures, subsequently extending lifespan and reducing mortality risk (as primary endpoints) and enhancing function and independence as secondary endpoints.

Keywords: 
Healthy aging
;  
Biomarkers
;  
Physical performance tests
;  
Cognitive function
;  
Metabolic health
;  
Longevity interventions
;  
Cardiovascular fitness
;  
Musculoskeletal strength
;  
Cognitive decline prevention
;  
Quality of life in elderly 
;  
Subject: 
Medicine and Pharmacology  -   Orthopedics and Sports Medicine

1. Introduction

Age distribution has been shifting upwards over the past few decades, creating both social and fiscal challenges. The economic consequences of an aging population drive political policies, influencing areas such as immigration, retirement age, and tax rates. These challenges are intensified when elderly individuals lack independence and the capacity to fulfill roles within their families, industries, and communities. Addressing the needs of an aging population requires a focus on building resilience in older adults to avoid substantial losses in quality of life for both the elderly and those who care for them.

2. Interventions for Improving Aging

Decline with age is not inevitable and can often be prevented or even reversed. Numerous interventions are available to support aging individuals, targeting various body systems. These include strategies to improve metabolic health, as well as enhancing physical and cognitive function.
Table 1. Physical measurements associated with aging and lifespan.
Table 1. Physical measurements associated with aging and lifespan.
. Physical marker Prediction
(Association with lifespan or health outcomes)
1. Treadmill stress test Cardiovascular fitness All cause mortality [1,2]
2. Sports participation Overall physical activity Lifespan [3]
3. Persistent vigorous activity Overall physical activity All cause mortality [4]
4. Physical activity energy expenditure Overall physical activity All cause mortality [5]
5. Leisure time physical activity Overall physical activity All cause mortality [6]
6. Grip strength Strength All cause mortality [7,8,9]
DunedinPoAm, PhenoAge and GrimAge clocks [10]
7. Sitting rise test Agility All cause mortality [11]
8. Gait speed Agility, Cardiovascular fitness All cause mortality [9]
9. Leg strength Strength, muscle mass All cause mortality [9]
10. Forced Expiratory Volume Respiratory fitness All cause mortality [9]
11. VO2 max Cardiovascular fitness All cause mortality [9,12]
Table 2. Associations of cognitive tests with lifespan-associated measures. Cognitive tests.
Table 2. Associations of cognitive tests with lifespan-associated measures. Cognitive tests.
Test Predictability
Cognitive Function Age [13]
Rate of cognitive decline Mortality risk [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36]
Cardiovascular mortality [37]
Motoric Cognitive Function Mortality Risk[38]

2.1. Metabolism

Poor metabolic function can contribute to a wide variety of illnesses. Those who are metabolically unwell (having metabolic multimorbidity) spend 52% more time as an inpatient in hospitals, have a 36% increased likelihood of not being able to perform activities of daily living (ADL)[39]. Metabolic dysregulation is comorbid with mental health disorders[40], cancer[41,42], neurodegenerative diseases[43,44].
Importantly, metabolic health can be readily changed through a shift in food consumption patterns. Any policy decision to tackle chronic disease must have food policy and agriculture at its core. Ultra processed foods (UPFs) comprise a larger proportion of people’s diet now than before, often for reasons of convenience. These UPFs with an often poor nutritional profile crowd out whole foods in the diet [45], and consumption is associated with an increased risk of all-cause mortality, cardiovascular disease, hypertension, metabolic syndrome, obesity, depression, cancer, gastrointestinal disorders [46] and frailty among others[47]. Factors positively associated with UPF consumption are male sex, young age, smoking (only significant for females) and living alone[46,48]. UPFs have significant and wide-ranging deleterious impacts on health[49].
Aging decreases resting metabolic rate (RMR), which is partially attributable to losses in fat-free mass (FFM, i.e., muscle and bone), though there is a decline independent of FFM[50]. Additionally central adiposity increases as one ages[51], and metabolic changes occur regularly, leading experts to classify metabolic dysregulation as hallmarks of aging[52]. Excess body fat can also alter hormone balance, as adipose tissue can promote estrogen production[53].
There is also significant crosstalk between metabolic health and brain health, where metabolically unhealthy individual have lower brain volumes into old age than their metabolically fit counterparts[54]. When it comes to healthy aging, it is important to avoid insulin resistance, as this is a significant predictor of age-related disease[55]. Those who live to ages past 100 (centenarians) have better insulin sensitivity than their counterparts who die at younger ages [56].
Endurance exercise can reduce age-related declines in mitochondrial oxidative capacity in individuals[57]. Overall, it is important to maintain metabolic health throughout one’s lifespan.
Much as one’s general fitness can be broken down into components of strength, speed, agility, balance, flexibility and more, one’s metabolic health can be operationalized through meaningful metrics.
First, examining function, we would want a metabolic system to extract energy from food, enough to perform all Activities of Daily Living (ADL), as well as be able to perform athletically when required. The food that people eat should grow and repair their bodies, and be sufficient to power all of the necessary functions that contribute to the basal metabolic rate (BMR).

2.2. Endurance

Endurance exercise, as opposed to punctuated, vigorous exercise, involves exerting power over a longer duration of time at a lower intensity than acute bursts. While this would appear to have limited applicability outside of endurance sports, one major desire of people is to have sustained energy throughout the day. Typically, energy levels are high in the morning, low in the early afternoon, and then increasing again before dropping again at night. Higher Body mass index and waist circumference are associated with higher levels of fatigue [58].
Most studies of energy levels of people look at those which suffer from fatigue due to an illness, and not quotidian fatigue. Several dietary conditions have been investigated for their effect on fatigue in disease contexts, and some literature exists on the impact of diet on fatigue in the context of physical training.
In chronic fatigue syndrome (CFS), adoptees of a low sugar and low yeast diet decreased their fatigue significantly (p=0.002, difference measured by the Chalder fatigue score) from their baseline measured before the dietary intervention[59].
A study of breast cancer survivors found that fatigue was associated with fat consumption, and negatively associated with carbohydrate and fiber consumption[60]. A meta-analysis on Multiple Sclerosis (MS) related fatigue came to similar conclusions, finding diets high in greens and low in fat[61], such as a modified paleo diet, may improve MS-related fatigue[62]. The meta-analysis also demonstrated low-quality evidence supporting folate and magnesium for decreasing fatigue[63]. Carbohydrate intake is positively associated with physical capacity, while fat consumption is negatively associated with physical performance in a six minute walk test and VO2max tests[64]. Omega 3 improved VO2 max, and vitamin D was associated with a nonsignificant improvement in VO2max. Paleolithic diets and Mediterranean diets improved fatigue in MS patients [65], as well as anti-inflammatory diets[66].
Chronic fatigue syndrome (CFS) is another condition where people have difficulty with energy levels. A 2017 meta-analysis showed improvements in fatigue for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10[67]. Omega 3, D-ribose, polyphenols and a multivitamin supplement also have support for their therapeutic use in CFS[68,69].
In the case of cancer related fatigue, adoption of the Mediterranean diet was associated with a small-moderate decrease in fatigue levels[70]. High protein[71], carnitine[72,73], Omega-3[74], American Ginseng[75], Wisconsin Ginseng[76] and Astralagus membranacus[77] reduced fatigue[78]. Guarana had mixed positive effects[79] and nonsignificant effects[80,81].
For weightlifters in the midst of weight loss, high protein consumption helped with fatigue [82]. For non-athletes losing weight, higher vegetable consumption was associated with lower levels of fatigue[83].

2.3. Cognition

One of the most feared outcomes of aging is a loss of cognition. Many elderly people do suffer from dementia, whether in mild or severe forms. This can be attributed to several mechanisms, some of which can be mediated through diet and lifestyle. First, mitochondrial function often degrades, and aggregates can form in the cases of full-blown Alzheimer’s disease. Other factors include decreased circulation, which can also precipitate hair loss.
As people age, they often become more set in their ways and are less likely to actively learn new things, despite, in retirement, having more leisure time than during their working life. In fact, retirement can have very negative mental health consequences for seniors, as the inactivity and seclusion can harm neural pathways.
Furthermore, one commonality in old age is a reduction of one’s social circle, as this often decreases as one increasingly becomes home bound. Old age homes may precipitate some social interaction in the common areas, but this is typically inadequate. Additionally, one social trend acting against senior cognitive health is that parents and children are decreasingly co-located in the same region, making visits more difficult.
The importance of regular social engagement for senior mental health has been studied, showing a significant impact of loneliness on senior health.
This impact often stretches back many years, where those with a more robust friend circle decades earlier also maintain a robust friend circle into old age. Therefore, the social circle is another ‘biomarker’ albeit unconventional, associated with successful aging. Here, relationships should be considered as a vital part of aging, as they present a vital support. Heart rate variability[84] and vagal nerve tone[85] are important biomarkers for stress tolerance.
Hobbies, including engagement with music[86], are associated with lower rates of cognitive decline and dementia[87,88,89]. Endurance exercise also prevents cognitive decline in older adults[90].

2.4. Cardiovascular and Pulmonary Health

Heart stroke volume from the heart increases with age, while heart rate decreases[91]. Maximum heart rate also decreases with age[92].
While total lung volume remains constant [93], respiratory strength decreases with age[94]. Aging causes a change in deep breathing where deep breathing is less able to increase the size of peripheral airways[95]
In addition, breath volume decreases with age, unless it is countervailed by physical activity.
Endurance exercise is excellent for aging people, as endurance exercise improves mitochondrial density[96] by enlargement of existing mitochondria[97,98].
can keep increasing, even as one grows older. The impacts of endurance exercise are cumulative, and people with histories of endurance exercise retain their endurance into advanced age.
Cardiopulmonary health can be assessed by the VO2 max test, which involves finding the maximal level of exertion and measuring the flow of oxygen at this level. VO2 max typically decreases with age, dropping more modestly in exercising individuals[99,100]
Given the trend of decreases in heart stroke volume and heart rate with increasing chronological age, VO2 max also declines with age, as it measures the combination of these factors along with respiratory capacity. It is important to retain VO2 max as one ages, and VO2 max helps with capacity to perform daily actions, such as walking up stairs. Additionally, endurance exercise also provides the metabolic benefits of increased mitochondrial density.
Another means by which older adults can improve their metabolic parameters is by cold exposure, which can facilitate the conversion of white adipose tissue to more metabolically active brown adipose tissue (BAT). This increases one’s basal metabolic rate and the practice can also improve one’s tolerance to cold. Older people, especially women, often feel cold at higher temperatures than their younger and male counterparts, so intentional cold exposure can help to alleviate this.
In addition to the cognitive benefits espoused above, periodic fasting can be important for metabolic parameters as well as improving cognitive function. Regular fasting can help to reduce blood sugar variation, which is a contributor to neurodegenerative diseases.
One common intervention that elderly people use is oxygen support. Approximately 1 in 5 people over the age of 70 have some form of chronic obstructive pulmonary disease[101]. Breathing pattern can impact the rates of respiratory illness, with mouth breathing contributing to the development of respiratory disorders[102,103]. One simple means of improving breathing performance is the practice of mouth taping, which involves taping one’s mouth shut during sleep, preferably using a tape that does not leave a residue. Participants in a study experienced significant improvements in rates of snoring and decreases in rates of apnoea events[104].
Ideally, in healthy aging we would prevent the need for supplementary oxygen. Being on cannula oxygen is often bulky and cumbersome, though newer models have reduced the mass to <10lbs (~3kg)[105].

2.5. Musculoskeletal (Strength and Stability)

Musculoskeletal fitness and stability are very important for older individuals to maintain their independence and sovereignty as they age. Without their own mobility, they are dependent on a caregiver, either paid, a family or friend, for their transportation needs. Paid caregivers can be financially taxing, and the relational caregivers may strain the relationship if one asks too often, creating resentment.
Hip fractures are a major reason for senior death, the one-year mortality after a hip fracture is 24%[106]. Additionally, the sense of autonomy ties into many other positive health circuits. If one is mobile, they can reap the benefits of exercise and the outdoors. If people are left indoors without social interaction, an extreme case being solitary confinement, mental health degrades quickly, and physical deterioration is fast.
Generally, after a certain age, muscle mass declines by a few percentage points per year[107,108]. This can be combatted through resistance training to increase muscle mass and improve both stability (to prevent falls) and strength (to resist injury in the case of falls). Vitamin D is associated with musculoskeletal strength [109] and may be an important intervention for maintaining strength in old age.

2.6. Psychosocial

Maintaining a positive life outlook throughout times of stress is associated with decreases in inflammation and future depressive symptom onset[110], additionally, an optimistic spirit is associated with healthier behaviours[111,112,113]. Optimism is a significant predictor of positive health outcomes[114], and improved quality of life in individuals experiencing disease[115]. Optimism can also have a positive impact on people close to the optimistic individual, as a spouse’s optimism is associated with the health of the other spouse[116]
Holding onto regret is a factor in lowered psychological well being in the aged [117,118], thought the emotional salience of missed opportunities is lesser in older people as opposed to young[119]. Forgiveness is also associated with increased well-being [120,121], including forgiveness of self[122]. Expressing and feeling gratitude is associated with life satisfaction [123,124,125].
Table 3. Intervention classes for maintaining physical function with age and means of training.
Table 3. Intervention classes for maintaining physical function with age and means of training.
Training Type Trend (absent training) System Associated tests and biomarkers Training Adaptations
Strength Training Sarcopenia, muscle loss, bone loss Musculoskeltal Grip Strength[126] Weightlifting Increase in muscle mass and bone density
Endurance training Lower VO2 max Metabolic, cardiopulmonary Resting Metabolic Rate,
Creatine phosphokinase[127]		 Running, swimming, walking, cycling, cross-country skiing, hiking, etc. Increased mitochondrial size, greater ability to metabolize fat, increased (heart) stroke volume
Balance training Poorer coordination Musculoskeletal, nervous Self-selected gait velocity [128], Chair rise test (timed 5 chair rises), Tandem standing and walking, timed up and go test, clinical gait analysis with special focus on regularity, mechanography [129] Yoga Neuromuscular control [130]
Flexibility Decrease in joint flexion[131,132] Musculoskeletal, tendons, fascia Flexibility tests: Flexindex[132] Yoga, Pilates Improved flexibility and stability
Preservation of genomic integrity Accumulation of mutations[133], accumulation of methylation, higher cancer rates[134] Genomic Integrity Telomere Length[135],
Methylation level [136]		 Low inflammation practices, avoiding carcinogenic exposures, possibly fasting[137] Possible improved immune surveillance [138]
Cognition Impairment on task switching[139], working and long-term memory [139] Nervous Cognitive tests[140]:
Mini-Mental State Examination,
Isaacs Set Test,
Benton Visual Retention Test,
Digit Symbol Substitution Test[141], Combined panel[142]		 Equivocal evidence for transfer effects of cognitive training[143],
Combined program (exercise, brain training and lecture)[144],
Reading[145],
Hobbies[146], Multilingualism[147], Dance[148], Social Activity [149], meditation[150]		 Increased BDNF and neurogenesis[151]preservation of white matter

3. Conclusion

This review highlights the importance of identifying and utilizing biomarkers to guide interventions aimed at promoting healthy aging. By clearly defining the major target outcomes and establishing links between these biomarkers and specific interventions, we can better understand how to enhance lifespan and health span. The integration of biomarker testing with tailored interventions presents a comprehensive strategy to improve the degree of independence among the aging population.
Our findings suggest that addressing key areas such as metabolism, cognitive function, cardiovascular and pulmonary health, musculoskeletal strength, and emotional well-being can significantly contribute to healthier aging. Implementing these strategies can mitigate the crisis of age-related chronic diseases, reduce healthcare expenditures, and lessen the societal burden associated with an aging demographic.
Future research should focus on refining these interventions and exploring the synergistic effects of combining multiple approaches. Policymakers and healthcare providers can leverage these insights to develop more effective programs and policies that support healthy aging, ultimately enhancing the quality of life for elderly individuals and benefiting society as a whole.
Currently, a large number of people are entering advanced age in Western countries, motivating strategies for lifespan extension. Without the maintenance of good health into late adulthood, older people are more prone to age-related chronic diseases, which consume many resources late in life.
With the adoption of testing and intervention strategies, functional decline with age may be ameliorated and the crisis lessened. This work presents a strategy to improve the degree of independence in the aging population over the non-intervention strategy.

Author Contributions

Conceptualization, M.H. and P.M.; methodology, M.H.; validation, M.H., P.M. and J.T.; investigation, M.H.; writing—original draft preparation, M.H.; writing—review and editing, M.H., P.M. and J.T. All authors have read and agreed to the published version of the manuscript.

Funding

The Article Processing Charge was funded by the Frontline Covid-19 Critical Care Alliance.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Acknowledgments

A preprint version of this article exists at [152].

Conflicts of Interest

The authors declare no conflicts of interest.

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