These long-lived cells are the most vulnerable to forms of age-related damage involving build up of metabolic waste products, and the related slow failure in the ability of cells to recycle their own damaged components. There is no fallback to replacing cells wholesale in this case, or at least not in our species, so long-lived cells must forge ahead and struggle to do their job no matter how damaged they are. The existence of these cells is a good argument for the need for in situ repair technologies, able to reverse damage and remove other hinderances in order to allow long-lived cells to regain their vigor and function - goals that are hard to attain with the present generation of cell replacement technologies emerging from the field of regenerative medicine.

Now consider this: it may be the case that some of the individual vital proteins in the machinery of long-lived cells are also never replaced. Some of your complex individual proteins, important cogs and gears in important cells, might be as old as you are. The very same sorts of concern about vulnerability surface here as well. Here is news of research in rats:

The scientists discovered that certain proteins, called extremely long-lived proteins (ELLPs), which are found on the surface of the nucleus of neurons, have a remarkably long lifespan. While the lifespan of most proteins totals two days or less, the Salk Institute researchers identified ELLPs in the rat brain that were as old as the organism. ... ELLPs make up the transport channels on the surface of the nucleus; gates that control what materials enter and exit. Their long lifespan might be an advantage if not for the wear-and-tear that these proteins experience over time. Unlike other proteins in the body, ELLPs are not replaced when they incur aberrant chemical modifications and other damage.

...

The fundamental defining feature of aging is an overall decline in the functional capacity of various organs such as the heart and the brain. This decline results from deterioration of the homeostasis, or internal stability, within the constituent cells of those organs. Recent research in several laboratories has linked breakdown of protein homeostasis to declining cell function. ... Most cells, but not neurons, combat functional deterioration of their protein components through the process of protein turnover, in which the potentially impaired parts of the proteins are replaced with new functional copies. Our results also suggest that nuclear pore deterioration might be a general aging mechanism leading to age-related defects in nuclear function, such as the loss of youthful gene expression programs.

Given how much longer humans live in comparison to rats, it may be that there are no proteins in the human body that never turn over. But I wouldn't be surprised to find that the situation for old humans is exactly the same as described above for old rats.

Link: http://www.eurekalert.org/pub_releases/2012-02/w-npr020112.php

Link: http://www.eurekalert.org/pub_releases/2012-02/uu-itr012612.php

One of the presentations given at last year's SENS5 conference was a look at turning the immune system against harmful aggregates of tau protein - as seen in Alzheimer's disease, for example, but which happens in all brains to some degree:

One of the perils of aging is the accumulation of various protein/peptide aggregates throughout the body, some of which are associated with toxicity. In several age-related disorders, aggregates of certain amino acid sequences are much more prominent than under normal conditions, and define the disease. Harnessing the immune system has emerged in recent years as a promising approach to treat these conditions. My laboratory has worked in this field targeting the amyloid-β peptide, the prion protein, the tau protein, and more recently the islet amyloid polypeptide. The focus of my talk will be on our tau immunotherapy studies. We have shown in tangle mouse models that active or passive immunizations clear pathological tau aggregates from the brain with associated functional benefits.

A thought to leave you with: the more we see the research community working on immunotherapies for age-related conditions, there more likely it becomes that significant investments will be made into reversing the decline of the immune system. The effectiveness of these therapies to a degree depends on the effectiveness of the immune system, and that progressively fails with age - having first generation therapies in the market will ensure that there exists a strong incentive to improve those therapies, and one of the most obvious ways to do that is to rejuvenate the immune system in elderly patients.

Link: http://online.wsj.com/article/SB10001424052970204740904577192901072611524.html