Lifestyle Optimization for Healthy Aging

By webnad

You may have noticed that some individuals look older than others despite being the same age. Since our genetics account for only 25% of the variation in human longevity, we have a great deal of control over how fast we age. We can’t stop the aging process, but we can attempt to slow it down or even reverse it. There are lifestyle choices we can make to reduce the chances of succumbing to age-related diseases, and these choices can potentially lead to a longer life. With aging research booming over the last few decades, scientists studies have again and again supported the benefits of exercise and diet while shedding light on particular lifestyle habits conducive to healthy aging that are not as well known. 

  1. Physical Activity
  2. Dietary Choices
    1. Fasting
      1. Time-Restricted Feeding
      2. Fasting-Mimicking Diet
    2. Dietary Styles
      1. Reducing Sugar Intake
      2. Vegetarian and Mediterranean Diet
  3. Sleep

Physical Activity

As we age, our muscles shrink, our bones become brittle, and blood flow to our organs is diminished, making it imperative to incorporate exercise into our lives. This is because exercise can make our muscles and bones stronger while enhancing blood flow to organs like the brain to keep us mentally sharp. 

As early as the age of 40, our muscles begin to shrink (atrophy) and become weaker. This age-related muscle decline is called sarcopenia and it accelerates as we grow older, especially after the age of 75. One key feature of muscle in older adults is a lack of nicotinamide adenine dinucleotide (NAD+), a vital molecule central in energy metabolism. It has been shown that exercise can increase NAD+ levels, which correlates with increased physical activity. Another study has shown that 20 minutes of cycling can raise NAD+ levels even in younger adults. Thus, exercise may be a good way to naturally increase NAD+, a molecule that declines with aging and may contribute to age-related diseases, including sarcopenia. 

(Janssens et al., 2022 | Nature Aging) Exercise May Rescue NAD+ Levels in Older Adults. Trained older adults have comparable NAD+ levels to young adults. NAD+ levels are depleted in normal and impaired older adults.

In addition to raising NAD+ levels, endurance exercise has been associated with protecting against telomere shortening. Telomeres are the bits of DNA at the ends of our chromosomes that tend to shorten as we age. Thus by keeping our telomeres long, exercise keeps our cells young. Furthermore, aerobic exercises like swimming, cycling, and jogging have been shown to rejuvenate our stem cells and reverse muscle aging in mice. While aerobic exercise has many benefits, such as increased bloodflow and enhanced cardiovascular health, resistance exercise like weight training provides additional benefits to older adults, including stronger bones and muscle.

Countless studies have demonstrated that regular exercise significantly reduces the chance of developing multiple age-related diseases like heart disease, type 2 diabetes, and cancer. Since these age-related diseases lead to premature death, exercise can potentially prolong lifespan by delaying or preventing these diseases. Interestingly, a study published in the British Journal of Sports Medicine found that American Olympic athletes on average live about five years longer than the general population. This doesn’t mean that you have to be an Olympic athlete to live longer, but it does suggest that regular exercise is beneficial to enhance overall health. While there is no standard exercise regimen, there are a few guidelines to help older adults get started with an exercise plan.

Dietary Choices


It’s no surprise that what we eat contributes heavily to how we age, and determining the best diet is no easy task. However, it may not be what we eat, but how much we eat that matters, as one element to pervade all diets is caloric restriction – limiting calories without malnourishment. Many studies have shown that caloric restriction increases the lifespan of various model organisms including yeast, fruit flies, and rodents. In humans, caloric restriction has been shown to reduce inflammation, which underlies many age-related diseases.

(Spadaro et al., 2022 | Science) The PLA2G7 Mediates Inflammatory Response. Caloric restriction inhibits the PLA2G7 gene leading to increased thymus function and decreased inflammation. 

One of the primary known benefits of caloric restriction is inhibition of the nutrient-sensing complex mTOR (mammalian target of rapamycin), a key modulator of cellular growth and protein synthesis. mTOR inhibition has been shown to activate a key anti-aging process known as autophagy – the removal of cellular waste – which has been shown to hamper cognitive decline and muscular dystrophy in animal models.

Another benefit of caloric restriction is heightended NAD+ levels. Raising NAD+ levels in animal models has been shown to prolong lifespan and mitiagte age-related diseases. NAD+ fuels enzymes called sirtuins which are important in longevity-associated processes like DNA repair. Raising NAD+ levels can also be achieved through supplmentation of it’s precurosrs like nicotinamide mononculeotide (NMN) and nicotinamde riboside (NR).

Since caloric restriction essentially tricks the body into going into self-preservation mode, it also activates survival factors like AMPK. AMPK as an enzyme that senses low energy, and when activated promotes cellular processes like the production of new mitochondria. Mitochondria are vital modulators of cellular energy and their dysfunction underlies the aging process. Like NAD+, AMPK can also be activated by exercise. In addition, AMPK can be activated by drugs like diabetes drug metformin. 

Time-Restricted Feeding

It’s important to note that limiting caloric intake is just one method of fasting that harnesses the health benefits of mTOR inhibition. Harvard aging scientist Dr. David Sinclair has continually touted the benefits of time-restricted feeding (TRF) – a form of fasting, whereby daily calories are consumed within an eight-hour period. Indeed, data has shown that TRF increases the lifespan of mice, especially when combined with caloric restriction. TRF also elevates beneficial molecules secreted by gut bacteria in mice, which leads to improved blood glucose levels and fat metabolism. However, TRF has it’s own restrictions, as feeding restricted to daylight hours increases fly lifespan, but feeding outside of these hours reduces lifespan. Indeed, according to a mouse study, it seems that fasting for extended periods of time is more beneficial to increasing lifespan than caloric restriction alone. Another method for caloric restriction called intermittent fasting — not eating for longer than a day — improves age-related frailty and cognition in mice. 

Fasting-Mimicking Diet

If dietary restriction is not something that fits your lifestyle, a fasting-mimicking diet may be the answer. The fasting-mimicking diet involves lowering mTOR by reducing consumption of branched-chain amino acids. The branched-chain amino acids (leucine, isoleucine, and valine) can be found in high amounts in protein rich foods like red meat, milk, and eggs. Limiting these foods could decrease mTOR activation.

If dieting just isn’t your thing, it may be worth trying so-called caloric restriction mimetics — supplements that mimic the benefits of caloric restriction. One candidate for such a mimetic is rapamycin, an FDA-approved drug that inhibits mTOR. Rapamycin can even be combined with dietary restriction, as a study in fruit flies found that combined treatment with rapamycin and a restricted diet led to lifespan increases that were greater than individual treatments alone. Notably, while dietary restriction and rapamycin both inhibit mTOR, studies have shown that each intervention traverses a unique, but overlapping set of metabolic pathways linked to aging. This means that combining both regimens could potentially target a wide variety of age-related conditions. Currently, there’s an ongoing clinical trial (NCT04488601) evaluating rapamycin’s longevity-boosting effects in healthy older adults.

Dietary Styles

While fasting and caloric restriction have been found to increase the lifespan of model organisms, it is difficult for many of us to follow and sustain such restrictive protocols for extended periods of time, let alone a lifetime. Therefore, an alternative would be to simply make dietary choices associated with increased lifespan and reduced disease in humans. If anything, these dietary styles can promote weight loss and reverse obesity, which is associated with several age-related diseases like diabetes and heart disease.

Reducing Sugar Intake

One dietary style to thrive for is eating less sugar. Consumption of too much sugar can lead to type 2 diabetes and possibly heart disease. Sugar also shuts off AMPK and sirtuins, which is counter to the known mechanism modulating increased lifespan. Thus, eating too much sugar is like lowering your defenses against disease and aging.

Vegetarian and Meditarranean Diet

A 2013 study showed that vegetarians live longer than non-vegetarians. Another study showed that the Mediterranean diet decreased biological aging. The Mediterranean diet consists of mostly plant foods, but also includes some fish. These diets, high in plant-based foods may be good for us because they are rich in molecules called polyphenols, which activate sirtuins.

Similar to the vegetarian and Mediterranean diet is the Sirtfood Diet. This diet specifically incorporates foods that are high in polyphenols to activate sirutins. Many celebrities have used this diet to shape up quickly, like musical artist Adele and UFC fighter Conor McGregor.


Maintaining good sleep patterns is vital to healthy aging. When our sleep-wake-cycle (circadian rhythm) becomes compromised, we’re susceptible to developing harmful diseases like heart disease, obesity, and type 2 diabetes. Lack of sleep also increases oxidative stress and exacerbates problems with daily activities like school, work, and social gatherings. Sleeping allows our body to recover from stress and perform to the best of its ability the following day. It also helps restore our immune system to better fight off infections and contributes to improved memory. Although scientists recommend getting at least 7-8 hours of sleep, certain circumstances may hinder one’s ability to do so. That being said, getting a few hours of sleep outweighs the risks of getting zero sleep.

  1. Acosta-Rodríguez V, Rijo-Ferreira F, Izumo M, Xu P, Wight-Carter M, Green CB, Takahashi JS. Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice. Science. 2022 May 5:e. doi: 10.1126/science.abk0297. Epub ahead of print. PMID: 35511946.
  2. Unnikrishnan A, Kurup K, Salmon AB, Richardson A. Is Rapamycin a Dietary Restriction Mimetic? J Gerontol A Biol Sci Med Sci. 2020 Jan 1;75(1):4-13. doi: 10.1093/gerona/glz060. PMID: 30854544; PMCID: PMC6909904.
  3. Passarino G, De Rango F, Montesanto A. Human longevity: Genetics or Lifestyle? It takes two to tango. Immun Ageing. 2016 Apr 5;13:12. doi: 10.1186/s12979-016-0066-z. PMID: 27053941; PMCID: PMC4822264.
  4. Janssens, G.E., Grevendonk, L., Perez, R.Z. et al. Healthy aging and muscle function are positively associated with NAD+ abundance in humans. Nat Aging (2022).
  5. Chong MC, Silva A, James PF, Wu SSX, Howitt J. Exercise increases the release of NAMPT in extracellular vesicles and alters NAD+ activity in recipient cells. Aging Cell. 2022 Jun 3:e13647. doi: 10.1111/acel.13647. Epub ahead of print. PMID: 35661560.
  6. Brett, J.O., Arjona, M., Ikeda, M. et al. Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1. Nat Metab 2, 307–317 (2020).
  7. de Resende-Neto AG, Aragao-Santos JC, Oliveira-Andrade BC, Silva Vasconcelos AB, De Sa CA, Aidar FJ, DeSantana JM, Cadore EL, and Da Silva-Grigoletto ME.  The Efficacy of Functional and Traditional Exercise on the Body Composition and Determinants of Physical Fitness of Older Women: A Randomized Crossover Trial.  J Aging Res, 2019; DOI: 10.1155/2019/5315376.
  8. Antero J, Tanaka H, De Larochelambert Q, Pohar-Perme M, Toussaint JF. Female and male US Olympic athletes live 5 years longer than their general population counterparts: a study of 8124 former US Olympians. Br J Sports Med. 2021 Feb;55(4):206-212. doi: 10.1136/bjsports-2019-101696. Epub 2020 Jul 29. PMID: 32727712.
  9. Spadaro O, Youm Y, Shchukina I, Ryu S, Sidorov S, Ravussin A, Nguyen K, Aladyeva E, Predeus AN, Smith SR, Ravussin E, Galban C, Artyomov MN, Dixit VD. Caloric restriction in humans reveals immunometabolic regulators of health span. Science. 2022 Feb 11;375(6581):671-677. doi: 10.1126/science.abg7292. Epub 2022 Feb 10. PMID: 35143297.
  10. Acosta-Rodríguez V, Rijo-Ferreira F, Izumo M, Xu P, Wight-Carter M, Green CB, Takahashi JS. Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice. Science. 2022 May 5:e. doi: 10.1126/science.abk0297. Epub ahead of print. PMID: 35511946.
  11. Danatas Machado, A.C., Brown, S.D., Lingaraju, A., et al. Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome. Cell Reports (2022)
  12. Pak, H.H., Haws, S.A., Green, C.L. et al. Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice. Nat Metab (2021).
To The Top